:iRollins, James (CMS/OCSQ) - Judicial Watch · From: Rollins, James (CMS/OCSQ) TO: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Rollins. James (CMS/OCSQ) (CMS/OCSQ) Leslye

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:iRollins, James (CMS/OCSQ)

IFrom: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, August 09,20102:01 PM To: Rollins, James (CMS/OCSQ) !

Subject: RE: Provenge MEDCAC questions 080910 team Ibj If-doc

! Sure!

From: Rollins, James (CMS/OCSQ) Sent: Monday, August 09, 2010 1:49 PM ,; To: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek,Eileen (CMS/OCSQ)

! Subject: RE: Provenge MEDCAC questions 080910 team Ibj If. doc ,

I am in agreement with question 7, but you might use it as an example. There may be other normograms available as a prognostic indicators for men in the same group. We should allow the MEDCA¢ committee to suggest other normogram they may be familiar with (if there are other options to use). Jarollins

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, August 09, 2010 1:30 PM To: PASERCHIA, LORI A. (CMS/OCSQ)i Rollins, James (CMS/OCSQ)i Pencek, Eileen (CMS/OCSQ) Subject: Provenge MEDCAC questions 080910 team Ibj If.doc !

Please see changes r made to question 7 and will verify with the FDA review dc)cuments.

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Obtained by Judicial Watch, Inc. via FOIA

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!.Rollins, James (CMS/OCSQ)

Fitterman, Leslye (CMS/OCSQ) ,From: Tuesday, August 10,20108:19 AM •Sent: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A.' (CMS/OCSQ); Pencek, Eileen To: (CMS/OCSQ) FW: NCA Question Subject:

FYI

-----Original Message----From: Jacques, louis B. (CMS/OCSQ) Sent: Monday, August e9, 2e1e6:52 PM To: Stieber, Joan (CMS/Ol); PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, leslye (CMS/OCSQ)

ICC: Saklas, Ariadne (CMS/Ol); Pettijohn, Juneous A. (CMS/Ol);: Syrek Jensen, Tamara S. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) . Subject: RE: NCA Question

Joan, '

Here's the boring story. We were aware of Provenge since Dendreon came in to see us quite awhile ago. We had no plans to do an NCD on it. Shortly after its FDA approval, we started to get low level inquiry from the press as to whether Medicare would cover Provenge. Then we saw some CMD questions as to whether Provenge was a vaccine (it J"as touted as a vaccine for prostate cancer even though it's not a vaccine in the usual ~ense) and therefore not coverable by Medicare. Then we started to see more questions!about whether it was really a drug and what benefit category it might have. So we started looking into it more, including chatting with CM about the benefit. Still we did not want to do an NCO.

Then we got a Congressional from Sen Webb asking about a spe~ific bennie. The MAC had stopped coverage because it became unsure if it was coverable. In following up that inquiry it became apparent that the MACs were going to be inconsistent about coverage (not unexpected given the small evidence base and that Provenge failed initial trials). So this looked like it would turn into a chronic Hill issue like Avastin. So I figured that if we did not do an NCD we'd eventually be asked to do one anyway, so might as w~ll just deal with it now. Otherwise we would only be hiding behind theMACs and makingi them take the heat. MMA 731 implies that NCDs should be done when there is Significant ~nconsistency in local contractor coverage.

So, I suppose the most direct cause of this NCO was the Hill.

As an aside FDA just warned Dendreon about misleading advertising about Provenge. I'll FW the story.

--~-~Original Message----From: Stieber, Joan (CMS/Ol) Sent: Mon 8/9/2e1e 4:58 PM To: Jacques, louis.B. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, leslye (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/Ol); Pettijohn, Juneous A. (CMS/Ol) Subject: RE: NCA Question

Thanks louis. Are you saying you have a FOIA request seeking an explanation of why you opened the NCA?

1


, And if so, does that preclude our sharing any information on it with this Congressional inquirer (Rep. Inslee, D-WA)? Or would those be 2 separate m~tters?

Also, is the fact that we have received a FOIA request disclo~able?

thanks -- Joan

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 09, 2010 4:50 PM , To: Stieber, Joan (CMS/OL)j '[email protected]'j PASERCHIA, LORI A. (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/OL)j Pettijohn, Juneous A. (CMS/OL) Subject: Re: NCA Question

We have a foia Sent from my Blackberry

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From: Stieber, Joan (CMS/OL) To: Jacques, Louis B. (CMS/OCSQ)j 'FITTERMAN, LESLYE K. (CMSjOCSQ)'j PASERCHIA, LORI A. (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/OL)j Pettijohn, Juneous A. (CMS/OL): Sent: Mon Aug 09 16:44:31 2010 Subject: FW:" NCA Question

Louis, Leslye, Lori - OL received an inquiry seeking more information on "what spurred CMS to open a NCA [on Provenge]".

Is there anything more you'd be willing to share about this, apart from what's already said on the coverage website? - e.g~, the Tracking Sheet says: "eMS received informal inquiries for a national coverage determination (NCO) for autologous cellular immunotherapy treatment of prostate cancer. This interest arose upon the recent FDA "approval of the Sipuleucel T treatment regimen, marketed as Provenge®."

thanks - Joan in OL

From: Saklas, Ariadne (CMS/OL) Sent: Monday, August 09, 2010 11:47 AM To: Stieber, Joan (CMS/OL) Cc: Pettijohn, Juneous A. (CMS/OL) Subject: FW: NCA Question

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Dear Joan:

I think I might have heard you mention something about this a~ stand-up. Are you able to speak to me and the staffer from Rep. Inslee's office about PROVENGE? Thanksl

Sincerely,

Ariadne Saklas

Health Insurance Specialist

Centers for Medicare and Medicaid Services

200 Independence Ave. SW

Washington, D.C. 20201

(202) 690-8606

(202) 690-8168 Fax

[email protected]

From: Pettijohn, Juneous A. (CMS/OL) Sent: Friday, August 06, 2010 4:08 PM To: Saklas, Ariadne (CMS/OL) Subject: FW: NCA Question

Check with Joan on this issue. Most likely she wants a conference calIon this.

Thanks.

From: Eidman, Megan [mailto:[email protected]] Sent: Friday, August 06, 2010 11:20 AM To: Pettijohn, Juneous A. (CMS/OL) Subject: NCA Question

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· - ': ".,.'

Hi Juneous,

'On June 30th, CMS opened a NCA to determine if Medicare wouldlcover PROVENGE, a prostate ,i cancer treatment. PRdVENGE, was approved by the FDA in April:i2010 for the treatment of minimally symptomatic metastatic prostate cancer. I am curio~s to know what spurred CMS to

: open a NCA, is there someone at CMS that I can speak to aboutlthis?

• Many thanks in advance for your help.

Best,

Megan

Megan Eidman

Legislative Assistant

Congressman Jay Inslee

403 Cannon HOB


202-225-6311

202-226-1606 (fax)

www.house.gov/inslee

[email protected]

4


,

i. ,

· Rollins, James (CMS/OCSQ)

From: Fitterman, Leslye (CMS/OCSQ) Tuesday, August 10, 2010 8: 19 AM Sent: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen To: (CMS/OCSQ)

Subject: FW: NCA Question

FYI

-----Original Message----From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 09, 2010 6:52 PM To: Stieber, Joan (CMS/OL); PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/OL); Pettijohn, Juneou~ A. (CMS/OL); Syrek Jensen, Tamara S. (CMS/OC5Q); Ashby, Lori M. (CMS/OCSQ) Subject: RE: NCA Question

Joan,

Here's the boring story. We were aware of Provenge since Deradreon came in to see us quite awhile ago. We had no plans to do an NCO on it. Shortly after its FDA approval, we started to get low level inquiry from the press as to whether Medicare would cover Provenge. Then we saw some CMD questions as to whether Provenge was a vaccine (it ~as touted as a vaccine for prostate cancer even though it's not a vaccine in the usual sense) and therefore not coverable by Medicare. Then we started to see more questions: about whether it was really a drug and what benefit category it might have. 50 we started looking into it more, including chatting with CM about the benefit. Still we did not want to do an NCO.

Then we got a Congressional~from Sen Webb asking about a specific bennie. The MAC had stopped coverage because it became unsure if it was coverable. In following up that inquiry it became apparent that the MACs were going to be inconsistent about coverage (not unexpected given the small evidence base and that Provenge failed initi~l trials). So this looked like it would turn into a chronic Hill issue like Avastin. So I figured that if we did not do an NCO we'd eventually be asked to do one anyway, so might as w.~ll just deal with it now. Otherwise we would only be hiding behind the MACs and making them take the heat. MMA 731 implies that NCDs should be done when there is significant inconsistency in local contractor coverage.

So, I suppose the most direct cause of this NCO was the Hill.

As an aside FDA just warned Dendreon about misleading advertising about Provenge. I'll FW the story.

~----Original Message----From: Stieber, Joan (CMS/OL) Sent: Mon 8/9/2010 4:58 PM I

To: Jacques, Louis B. (CMS/OCSQ); PA5ERCHIA, LORI A. (CMS/O~SQ); Fitterman, Leslye (CMS/OC5Q) \ Cc: Saklas, Ariadne (CMS/OL); Pettijohn, ]uneous A. (CMS/OL)

Subject: RE: NCA Question

Thanks Louis. Are you saying you have a FOIA request seeking an explanation of why you opened the NCA?

1


And if so, does that preclude our sharing any information on it with this Congressional inquirer (Rep. Inslee, D-WA)? Or would those be 2 separate matters?

Also, is the fact that we have received a FOIA request disclo~able?

thanks -- Joan

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 09, 2010 4:50 PM To: Stieber, Joan (CMS/OL)j '[email protected]'j PASERCHIA, LORI A. (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/OL)j Pettijohn, Juneous A. (CMS/OL) Subject: Re: NCA Question

We have a foia Sent from my Blackberry

From: Stieber, Joan (CMS/OL) To: Jacques, Louis B. (CMS/OCSQ); 'FITTERMAN, LESLYE K. (CMSjOCSQ)'; PASERCHIA, LORI A. (CMS/OCSQ) Cc: Saklas, Ariadne (CMS/OL); Pettijohn, Juneous A. (CMS/OL)' Sent: Mon Aug 09 16:44:31 2010 Subject: FW: NCA Question

Louis, Leslye, Lori - OL received an inquiry seeking more information on "what spurred CMS to open a NCA [on Provenge]".

Is there anything more you'd be willing to share about this, ,apart from what's already said on the coverage website? - e.g., the Tracking Sheet says: "C~S received informal inquiries for a national coverage determination (NCO) for autologous cellular immunotherapy treatment of prostate cancer. This interest arose upon the recent FDA approval of the Sipuleucel T treatment regimen, marketed as Provenge®."

thanks'- Joan in OL

From: Saklas, Ariadne (CMS/OL) Sent: Monday, August 09, 2010 11:47 AM To: Stieber, Joan (CMS/OL) Cc: Pettijohn, Juneous A. (CMS/OL) Subject: FW: NCA Question

2


Dear Joan:

I think I might have heard you mention something about this at stand-up. Are you able to speak to me and the staffer from Rep. Inslee's office about PROVENGE? Thanks!

Sincerely,

Ariadne Saklas

Health Insurance Specialist

Centers for Medicare and Medicaid Services

200 Independence Ave. SW


(202) 690-8606

, (202) 690-8168 Fax

[email protected]

From: Pettijohn, Juneous A. (CMS/OL) Sent: Friday, August 06, 2010 4:08 PM To: Saklas, Ariadne (CMS/OL) Subject: FW: NCA Question

Check with Joan on this issue. Most likely she wants a conference calIon this.

Thanks.

From: Eidman, Megan [mailto:[email protected]] Sent: Friday, August 06, 2010 11:20 AM To: Pettijohn, Juneous A. (CMS/OL) Subject: NCA Question

3


Hi Juneous~

On June 30th~ CMS opened a NCA to determine if Medicare would.: cover PROVENGE~ a prostate cancer treatment. PROVENGE~ was approved by the FDA in April 2010 for the treatment of minimally symptomatic metastatic prostate cancer. I am curious to know what spurred CMS to open a NCA~ is there someone at CMS that I can speak to abou~ this?

Many thanks in advance for your help.

Best~

Megan

Megan Eidman

Legislative Assistant

Congressman Jay Inslee

403 Cannon HOB

Washington~ D.C. 20515

202-225-6311

202-226-1606 (fax)

www.house.gov/inslee

[email protected]

4


·t.;.;R;.;o~lr;.;.;m;;;.s~.J;.;a;;.;.;m;.;.;;e;;s~(_C.;.;,M;,;;;;S;;.;IO;;.C;;.S;;.Q;;,),--_________________________

Wittenberg, Kim (AHRQ/COE) .From: , Sent: Tuesday, August 10, 2010 10:27 AM

Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B.To: (CMS/OCSQ); Schott, Lawrence H. (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) . Subject: Provenge (CANP0610) timeline

Attachments: CANP0610 Provenge Prostate WAdoc

Good morning, Since the MedCAC date is set for Provenge, I've added in more detailed dates to the WA (attached). Once we know the available dates for the Evidence Forum, we'll be set. Thank you, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639 E-mail: [email protected]

From: Rollins, James (CMS/OCSQ) Sent: Thursday, July 29, 2010 1:47 PM TO: Wittenberg, Kim (AHRQ/COE); Fitterman, Leslye (CMS/OCSQ) Subject:RE: Provenge MedCAC

Not yet, will let you know. jarollins

From: Wittenberg, Kim (AHRQ/COE) Sent: Thursday, July 29, 2010 11:08 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: Provenge MedCAC

Good morning,

Do we have a confirmed date for the Provenge MedCAC? Thank you in advahce for this information.

Sincerely, Kim

Kim Marie Wittenberg, MA

Agency for Healthcare Research and Quality

Center for Outcomes and Evidence

540 Gaither Road, Room 6018

1


Rockville. MD 20850

Ph: 301-427-1488

Fax: 301-427-1639

E-mail: [email protected]

2


Rollins. James (CMS/OCSQ)

, From: Fitterman, Leslye (CMS/OCSQ) Tuesday, August 10, 2010 10:37 AM . ,Sent: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Jacques, Louis B.To: (CMS/OCSQ); Schott, Lawrence H. (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) RE: Provenge (CANP0610) timeline Subject:

Thank you Kim.

From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, August 10, 2010 10:27 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Schott, Lawrence H.

(CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: Provenge (CANP0610) timeline

Good morning, Since the MedCAC date is set for Provenge, I've added in more detailed dates to the WA (attached). Once we know the available dates for the Evidence Forum, we'll be set. Thank you,

. Kim


From: Rollins, James (CMS/OCSQ) Sent: Thursday, July 29, 2010 1:47 PM To: Wittenberg, Kim (AHRQlCOE); Fitterman, Leslye (CMS/OCSQ) Subject: RE: Provenge MedCAC

Not yet, will let you know. jarollins

From: Wittenberg, Kim (AHRQ/COE) Sent: Thursday, July 29, 2010 11:08 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: Provenge MedCAC

Good morning,

Do we have a confirmed date for the Provenge MedCAC? Thank you in adva,nce for this information.

Sincerely, Kim

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Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


2


Rollins, James (CMS/OCSQ)

From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, August 11, 2010 11:10 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, EileE¥n (CMS/OCSQ) Subject: Provenge MEDCAC questions 081110 team Ibj If.doc Attachments: Provenge MEDCAC questions 081110 team Ibj If.doc

I have updated question 7 to reflect the variables (e.g., stratification and confqunders) in the IMPACT study. Jim, if you don't want to send the changes to Louis just let me know. '

Thanks, Leslye

1 I,

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.I

: Rollins, James (CMS/OCSQ)

From: Ellis,· Maria A. (CMS/OCSQ) Sent: Wednesday, August 11,20102:18 PM To: Rollins, James (CMS/OCSQ)

, Subject: RE: Provenge MEDCAC questions 081110 team Ibj If.doc

Th~y 'were sent but they can be resent.

IIeal1lJ hlsllr;111ce Specialist Division ofOperations and In/()I7l1alionMallagemeni Coverage illldAIlalysis (;rolJp, OGS'Q (410) 786-0309

[email protected]

From: Rollins, James (CMSjOCSQ) Sent: Wednesday, August 11, 2010 1:53 PM To: Ellis, Maria A. (CMSjOCSQ) Subject: FW: Provenge MEDCAC questions 081110 team Ibj If.doc

Maria, have the MEDCAC questions been forwarded to Cliff and Saty yet? If not, DON'T send them just yet-we just revised question 7. They need to go to Louis first before going to Cliff and Saw: Jarollins

From: Fitterman, Leslye (CMSjOCSQ) Sent: Wednesday, August 11, 2010 11:10 AM To: Rollins, James (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ) Subject: Provenge MEDCAC questions 081110 team Ibj If.doc

I have updated question 7 to reflect the variables (e.g., strMification and confounders) in the IMPACT study. Jim, if you don't want to send the changes to Louis just let me know.

Thanks, Leslye

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From: Pencek, Eileen (CMS/OCSQ) Sent: Wednesday, August 11,201012:58 PM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ) . ; Subject: RE: Provenge MEDCAC questions 081110 teamlbrlf.doc

Leslye, .. Ilike the additions, especially the prior chemotherapy one. It forces the discussion rather than asking Cliff and Sady to make sure it gets addressed. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, August 11, 2010 11:10 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A.(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Provenge MEDCAC questions 081110 team Ibj If.doc

I have updated question 7 to reflect the variables (e.g., stratification and confounders) in the IMPACT study. Jim, if you don't want to send the changes to Louis just let me know.

Thanks, Leslye

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!Rollins, James (CMS/OCSQ)

. From: Atkinson, Michelle L. (CMS/OCSQ) :Sent: Thursday, August 12,20108:07 AM . '. To: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Rollins, James (CMS/OCSQ) . Cc: Ellis, Maria A. (CMS/OCSQ); Lund, Eleanor L. (CMS/OCSQ); Graves, Patricia A.

(CMS/OCSQ) , Subject: Timeline for the November MEDCAC : Attachments: Nov 17 timeline, DOC

Attached is the timeline for the Nov meeting. This is just something to keep everyone on track.

. If you have any questions please let us know.

Thank you Michelle

Michelle Atkinson OCSQ/CAG/DOIM 410-786-2881

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. Rollins, James (CMS/OCSQ)

. From: Kouzoukas, Demetrios ([email protected]] : Sent: Thursday, August 12, 2010 3:55 PM

Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) To: Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

To all:

As a result of our discussions, our client posted their comment, which containedithe views of the scientists I was referring to (see http://www.cms.gov/mcd/publiccomment popup.asp?comment id=21612). If you should need any further information or follow-up on the topic or comment, please do not hesitate to be in touch (202-662-5057). Thank you again for your help on such short notice.

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediatidy advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system.:Thank you for your cooperation.

From: Kouzoukas, Demetrios Sent: Thursday, July 29, 2010 2:17 PM . To: Rollins, James (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ) Cc: Dolina, Elaine L. (CMSjOCSQ) Subject: RE: follow-up and background

. Thank you for the information. Our client is working to provide comments to CMS that will be as helpful as possible under the circumstances.

The tracking sheet at https:llwww.cms.gov/mcd/viewtrackingsheet.asp?id=247 says the comment period is "6/30/2010- 7/30/2010," which indicates that the website will be available until 11 :59 PM on July 30. Is that correct, and is that time Eastern daylight time?

-- Demetrios

This message is from a law firm and may contain information that is corifidential or legally privileged. Ij you are not the intended recipient, please immediately advise the 'sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Rollins, James (CMSjOCSQ) [mailto:[email protected]] Sent: Tuesday, July 27, 2010 2:35 PM· To: Koutoukas, Demetrios; Fitterman, Leslye (CMS/OCSQ)

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Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Demetrios, thank you for your comments. I have revieweq the wording of the document that you sent us and feel that it is not necessary. In order to more effectively serve the Medicare population, we need credible information to help us make ,our decisions. As noted in the previous correspondence, CMS takes all statements from commentbrs seriously, whether or not they are given with consent or anonymously. Also CMS cannot guarantee that names of commenters will not be released to the public. I hope that this information will help you in your efforts. Jarollins

From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Monday, July 26, 2010 9:08 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you very much. Your prompt attention and furtherinquifY is most helpful and appreciated. Unfortunately, if we are to have a realistic chance at getting these comments in, the commenters would need to hear back by end of day tomorrow. Is that feasible?

In the interests of expediting matters, I offer the following potential language for commenters to use:

"I am concerned about the disclosure of my identity in making these comments, and therefore I am providing the information in these comments on th~ condition that my identity (including name, email address, IP address, employer, any other affiliation) is considered "personnel and medical files and similar files the disclosure of which vYould constitute a clearly unwarranted invasion of personal privacy" in a "system of records" and therefore protected from release under the Privacy Act of 1974 (section (b)) and the Freedom of Information Act (exemption (b)(6))."

-- Demetrios

This message is from a law firm and may contain informqtion that is confidential or legally privileged.lfyou are not the intended recipient, please immediately advise the sender by reply email that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Fitterman, Leslye (CMS/OCSQ) [mailto:[email protected]] Sent: Friday, July 23, 2010 2:35 PM To: Kouzoukas, Demetrios Cc: [email protected]; [email protected] Subject: Re: follow-up and background

We anticipate a respond by the end ofnext week before the comment period ends. We have confirmed that all anonymous comments are considered as credible.

Sent from my iPhone

On Ju123, 2010, at 4:29 PM, "Kouzoukas, Demetrios" <[email protected]> wrote:

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Is there any more information, or perhaps draft language, I can provide to help you consider how best to proceed at this point?

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply e~mail that this message has been inadvertently transmitted to you and 4elete this e-mail from your system. Thank you for your cooperation. .

From: Kouzoukas, Demetrios Sent: Thursday, July 22, 2010 2:01 PM To: [email protected] [email protected] [email protected] Subject: follow-up and background

James, Leslye, and Elaine:

Here is the article I referenced in my conversations with James and Leslye. If you are open to the procedure I discussed with Leslye -- whereby a commenter could request that their identity not be released, I would be pleased to propose language that such commenters could use and on which basis CMS would then oblige the request.

Thank you very much for your consideration.

« File: Cancer Experts Threatened A. .. pdf»

-- Demetrios

Demetrios L. Kouzoukas Covington & Burling LLP 1201 Pennsylvania Avenue, NW Washington, DC 20004-2401 http://www.cov.com/dkouzoukas! [email protected] Tel: 202.662.5057 Assistant: Dee Perkins (202.662.6003, [email protected]) Fax: 202.7785057 . download vcard: http://www .cov .comlbiographies/vcard.aspx? Attomey= 13540

This message is from a law firm and may; contain information that is confidential or legally privileged. Ifyou qre not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation. ..

3


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; Rollins, James (CMS/OCSQ)

From: Wittenberg, Kim (AHRQ/COE) Sent: Friday, August 13, 2010 4:20 PM To: Rollins,James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: FW: CANP0610_Sipuleucel T search strategy incl e~cI_081110 Attachments: CANP061 O_Sipuleucel T search strategy incl excl_08111 O.docx

Importance: High

Good afternoon, Attached is the search strategy and inclusion/exclusion criteria for CANP0610 (p;rovenge TA). Please respond with any comments. Thank you and have a good weekend, Kim





Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


From: Ziegler, Kathleen [mailto:[email protected]] Sent: Wednesday, August 11, 2010 5: 11 PM To: Wittenberg, Kim (AHRQ/COE) Cc: Mark, David; Sarsany, Lisa Subject: CANP0610_Sipuleucel T search strategy inc! excL081110

Kim:

Attached is the search strategylinclusion-exclusion criteria deliverable for the sipuleucel-T technology assessment. Please let me know if you have any questions.

Kathleen

Kathleen M. Ziegler, Pharm.D. Director, Clinical Science Services Technology Evaluation Center (TEC) Blue Cross and Blue Shield Association

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225 N. Michigan Avenue, 5th floor Chicago, IL 60601 (P) 312.297.6491 (F) 312.297.5586

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iRollins. James (CMS/OCSQ)

'From: Wittenberg, Kim (AHRQ/COE) 'Sent: Friday, August 13, 20104:20 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMp/OCSQ); Berliner, Elise (AHRQ) Subject: FW: CANP0610_Sipuleucel T search strategy incl ex,cL081110

1Attachments: CANP0610_Sipuleucel T search strategy incl excl_081110.docx

: Importance: High

Good afternoon, 'Attached is the search strategy and inclusion/exclusion criteria for CANP0610 (Provenge TA). Please respond with any comments .

. Thank you and have a good weekend, Kim





Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


Fro~~~Zi~ler, K;hl~~n [m~;;;;thi~~~2;~i;@bd;"~~]-~'~'-'--'~-'"~~~--.-.~.•~.-.~---..- .••-'~.-

Sent: Wednesday, August 11, 2010 5: 11 PM To: Wittenberg, Kim (AHRQltOE) Cc: Mark, David; Sarsany, Lisa Subject: CANP0610_Sipuleucel T search strategy incl excl_081110

Kim:

Attached is the search strategy/inclusion-exclusion criteria deliverable for the sipuleucel-T technology assessment. Please let me know if you have any questions. .

Kathleen

Kathleen M. Ziegler, Pharm.D. Director, Clinical Science Services Technology Evaluation Center (TEC) Blue Cross and Blue Shield Association

1



2


: Rollins, James (CMS/OCSQ)

From: Kouzoukas, Demetrios [[email protected]] Sent: Friday, August 13,20105:49 PM . To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

It occurs to me that the following summary of the comments submitted below might also be helpful to you: . I

• Administering Provenge involves processing a patient's blood to initially! remove 90% of a patient's circulating, cancer--fighting immune cells, which are then further purified and treated to make Provenge. This 'manufacturing' process has the side effect of causing the loss of >50% of these immune cells.

• When the trials for Provenge were conducted, the control group also underwent the removal and processing of these immune cells. But instead of reinjecting all the remaining cells into the subjects, two-thirds of them were frozen and preserved for possible later treatment with Provenge.

• Therefore, at each of three sessions, the experimental group lost ':"50o/~ of these cells in their system at the time and placebo patients lost -86%.

• A normal, healthy adult, can lose the number of cells at issue in the control and Provenge groups without negative consequences. Therefore, the difference between the control and experimental groups was not thought to be clinically significant.

• However, as opposed to normal, healthy adults, the loss of such a great quantity of these cells is significant in an elderly population and is even more significant in an elderly population with advanced prostate cancer.

• Experts who understand how massively the immune system changes around age 70 have categorically told us that elderly patients are harmed if these cells are removed, because t~eir bodies are not able to replace the removed cells with equally vigorous or the same types of replacement cells. The consequence is a shortened survivaJ, particularly in patients with active cancer. This nuance regarding older patients is one that has emerged in the field of immune aging after the Provenge trials were originally designed.

• While the Provenge trials took away a much greater percentage of immune cells from placebo patients than from Provenge patients, patients under 65 were not affected by either level of removal and lived longest (all patients <65 lived 28-29 months in the trials). Older patients with 50% of cells;removed lived 5.5 months less than the 29 months seen in younger patients from that arm and older patients with 86% of cells removed lived 11 months les than the 28.2 months seen in younger patients from that arm.

1


• Some might interpret these results to conclude that Provenge is simply le~s effective for older patients than it is for younger patients. But these shorter survival periods for older patient~ may well instead demonstrate that older) patients across-the-bard are harmed by the Provenge process -- with thdse who had greatest cell loss (the control group) harmed most.

• It is possible, if not likely, that older patients are better off not undergoing the Provenge treatment and thereby losing so many of these vital cells. There was no such control group in the Provenge trials.

• ONLY immune aging experts (experts that study thymic decline, T cell re,ceptor diversity declines, na'ive T cell population declines, etc.) have the expertise pivotal to identifying the impact of the trial design on the actual outcomes for Provenge in older patients. Immunologists who do not have this immune aging expertise focus on more general data and knowledge, which reflects the population as a whole and therefore is more reflective of the population under age 65. Such immunologists would be correct in believing that this cell loss is not meaningful to the average patient in the general population. In contrast, immune aging experts follow the knowledge developed by scientists in the last decade about the frailty of the aged immune system.

• If such immune aging experts are not involved in the analysis, the impact of the trial design on the actual outcomes for Provenge in older patients will very likely be misunderstood.

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged Ifyou are not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Fitterman, Leslye (CMSjOCSQ) [mailto:[email protected]] sent: Thursday, August 12, 2010 4: 16 PM To: Kouzoukas, Demetrios; Rollins, James (CMSjOCSQ) . Cc: Dolina, Elaine L. (CMSjOCSQ) Subject: RE: follow-up and background

Thank you!

From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Thursday, August 12,20103:55 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

To all:

As a result of our discussions, our client posted their comment, which contained the views of the scientists I was referring to (see http://www.cms.gov/mcd/publiccomment..,popup.asp?comment id=21612). If you should need any further information or follow-up on the topic or comment, please do not hesitate to be in touch (202-6625057). Thank you again for your help on such short notice.

-- Demetrios

2


This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by r~ply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system.' Thank you for your cooperation.

From: Kouzoukas, Demetrios Sent: Thursday, July 29,20102:17 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you for the information. Our client is working to provide comments to CMS that will be as helpful as possible under the circumstances.

The tracking sheet at https:llwww.cms.gov/mcd/viewtrackingsheet.asp?ia=247 says the comment period is "6/3012010 - 713012010," which indicates that the website will be available until 11:59 PM on July 30. Is that correct, and is that time Eastern daylight time?

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by ~eply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Rollins, James (CMS/OCSQ) [mailto:[email protected]] . Sent: Tuesday, July 27,20102:35 PM To: Kouzoukas, Demetrios; Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CM~/OCSQ) Subject: RE: follow-up and background

Demetrios, thank you for your comments. I have reviewed the wording of the document that you sent us and feel that it is not necessary. In order to more effectively serve the Medicpre population, we need credible information to help us make our decisions. As noted in the previous correspondence, CMS takes all statements from commenters seriously, whether or not they are given with consent ~r anonymously. Also CMS cannot guarantee that names of commenters will not be released to the pUblic. I hope that this information will help you in your efforts. Jarollins

From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Monday, July 26,20109:08 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you very much. Your prompt attention and further inquiry is most helpful and appreciated. Unfortunately, if we are to have a realistic chance at getting these comments in, the commenters would need to hear back by end of day tomorrow. Is that feasible? I


"I am concerned about the disclosure of my identity in making these comments, and therefore I am providing the information in these comments on the condition that my identity (including name, email address, IP address, employer, any other affiliation) is considered "personnel and medical files and similar files the disclosure of which would constitute a clearly unwarranted invasion ofpersonal privacy" in a "system of records" and

3


therefore protected from release under the Privacy Act of 1974 (section (b)) and the Freedom of Information Act (exemption (b)(6))."

-- Demetrios

. This message is from a law jirm and may contain information that is conji(iential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply e·mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

, From: Fitterman, Leslye (CMS/OCSQ) [mailto:[email protected]] Sent: Friday, July 23, 2010 2:35 PM .,

.. To: Kouzoukas, Demetrios Cc: [email protected]; [email protected]

i Subject: Re: follow-up and background

. We anticipate a respond by the end of next week before the comment pedod ends. We have confirmed that all anonymous comments are considered as credible.

Sent from my iPhone


Is there any more information, or perhaps draft language, I can provide to help you consider how best to proceed at this point?

-- Demetrios

This message is from a law jirm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. :Thank you for your cooperation.

From: Kouzoukas, Demetrios

Sent: Thursday, July 22,20102:01 PM

To: [email protected]; [email protected]; [email protected]

Subject: follow-up and background


Here is the article I referenced in my conversations with James and Leslye. If you are open to the procedure I discussed with Leslye -- whereby a commenter could request that their identity not be released, I would be pleased to propose language that such commenters could use and on which basis CMS would then oblige the request.


«File: Cancer Experts Threatened A ... pdf»

-- Demetrios

Demetrios L. Kouzoukas

Covington & Burling LLP

1201 Pennsylvania Avenue, NW Washington, DC 20004-2401

http://www.cov.com/dkouzoukas/

4


· [email protected]

Tel: 202.662.5057

: Assistant: Dee Perkins (202.662.6003, [email protected])

· Fax: 202.778.5057

; download vcard: http://www.cov .comlbiographies/vcard.aspx?Attorney= 13540

; This message is from a law firm and may contain information that is confi,dential or legally privileged. Ifyou · are not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

5


Rollins, James (CMS/OCSQ) ('

From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, August 13, 20106:13 PM To: Kouzoukas, Demetrios Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ) Subject: Re: follow-up and background

Thank you for your message.

Sent from my iPhone

On Aug 13,2010, at 5:50 PM, "Kouzoukas, Demetrios" <[email protected]> wrote:

It occurs to me that the following summary of the comments submitted ,below might also be helpful to you:

• Administering Provenge involves processing a patient's blood .ito initially remove 90% of a patient's circulating, cancer--fighting immune cells, which are then further purified and treated to make Provenge. This 'manufacturing' process has the side effect of causing the loss of >50% of these immune cells. ..

• When the trials for Provenge were conducted, the control gro~p also underwent the removal and processing of these immune cells. But instead of reinjecting all the remaining cells into the subjects, two-thirds of them were frozen and preserved for possible later treatment with Provenge,

• Therefore, at each of three sessions, the experimental group ,lost -50% of these cells in their system at the time and placebo patients lost -86%.



• Experts who understand how massively the immune system changes around age 70 have categorically told us that elderly patients are harmed if these cells are removed, because their bodies are not able to replace the removed cells with equally: vigorous or the same types of replacement cells. The consequence is a shortened survival, particularly in patients with active cancer. This nuance regarding older patients is one that has emerged in the field of immune aging after the Provenge trials were originally designed.

1


• While the Provenge trials took away a much greater percentage of immune cells from placebo patients than from Provenge patients, patients under 65 were riot affected by either level of removal and lived longest (all patients <65 lived 28-29 months in the trials). Older patients with 50% of cells removed lived 5.5 months less than the 29 months seen in younger patients from that arm and older patients with 86% of cells removed lived 11 months les than the 28.2 months seen in younger patients from that arm. '

• Some might interpret these results to conclude that Provenge is simply less effective for older patients than it is for younger patients. But these shorter survival periods for older patients may well instead demonstrate that older patients across-the-bard are harmed by the Provenge process -- with those who had greatest cell loss (the control group) harmed most.

• It is possible, if not likely, that older patients are better off not undergoing the Provenge treatment and thereby losing so many ofthese vital cells. There was no such control group in the Provenge trials. .

• ONLY immune aging experts (experts that study thymic deClin·e, T cell receptor diversity declines, naIve T cell population declines, etc.) have the expertise pivotal to identifying the impact of the trial design on the actual outcomes for Provenge in older patients. Immunologists who do not have this immune aging expertise focus on more general data and knowledge, which reflects the population as a whole and therefore is more reflective of the population under age 65. Such immunologists would be correct in believing that this cell loss is not meaningful to the average patient in the general population. In contrast, immune aging experts follow the knowledge developed by scientists in the last decade about the frailty of the aged immune system.


-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply email that this message has been inadvertently transmitted to yOU and delete this e-mail from your system. Thank youfor your cooperation.

From: Fitterman, Leslye (CMS/OCSQ) [mailto:[email protected]] Sent: Thursday, August 12, 20104:16 PM To: Kouzoukas, Demetriosi Rollins, James (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you!

2


From: Kouzoukas, Demetrios [mailto:dk:[email protected]] Sent: Thursday, August 12,20103:55 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

To all:

As a result of our discussions, our client posted their comment, which contained the views of the scientists I was referring to (see http://www.cms.gov/mcd/publiccomment popup.asp?comment id'=21612). If you should need any further information or follow-up on the topic or comment, ple~se do not hesitate to be in touch (202-662-5057). Thank you again for your help on such shoit notice.

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged Ifyou are not the intended recipient, please immediately advise the sender by reply email that this message has been inadvertently transmitted to you dnd delete this e-mail from your system. Thank you for your cooperation.

from: Kouzoukas, Demetrios Sent: Thursday, July 29, 2010 2:17 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you for the information. Our client is working to provide cpmments to CMS that will be as helpful as possible under the circumstances.

The tracking sheet at https:llwww.cms.gov/mcd/viewtrackingsheet.asp?id=247 says the comment period is "6/30/2010- 713012010," which indicates that the website will be available until 11 :59 PM on July 30. Is that correct, and is that time Eastern daylight time?

-- Demetrios

This message is from a law firm and may contain information thqt is confidential or legally privileged Ifyou are not the intended recipient, please immedia~ely advise the sender by reply email that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Rollins, James (CMS/OCSQ) (mailto:[email protected]] Sent: Tuesday, July 27, 2010 2:35 PM To: Kouzoukas, Demetrios; Fitterman, Leslye (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Demetrios, thank you for your comments. I have reviewed the wording of the document that you sent us and feel that it is not necessary. In order to more effectively serve the Medicare population, we need credible information to help us make our decisions. As noted in the previous correspondence, CMS takes all statements from commenters seriously, whether or not they are given with consent or anonymously. Also CMS cannot guarant~e that names of commenters will not be released to the public, I hope that this information will h~lp you in your efforts. Jarollins

I

3


From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Monday, July 26,20109:08 PM To: Fitterman, Leslye (CMS/OCSQ) , Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ) Subject: RE: follow-up and background

Thank you very much. Your prompt attention and further inquiry i~ most helpful and appreciated. Unfortunately, if we are to have a realistic chance at ~etting these comments in, the commenters would need to hear back by end ofday tomorrow. Is that feasible?


"I am concerned about the disclosure of my identity in making these comments, and therefore I am providing the information i~ these 90mments on the condition that my identity (including name, email address, IP address, employer, any other affiliation) i$ considered "personnel and medical files and similar files the disclosure of which would consthute a clearly unwarranted invasion of personal privacy" in a "system of records" and therefore protected from release under the Privacy Act of 1974 (section (b)) and the Freedom ofInformation Act (exemption (b)(6))."

-- Demetrios

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply email that this message has been inadvertently transmitted to you qnd delete this e-mail from your system. Thank you for your cooperation.

From: Fitterman, Leslye (CMS/OCSQ) [mailto:[email protected]] Sent: Friday, July 23,20102:35 PM . To: Kouzoukas, Demetrios Cc: [email protected]; [email protected]~v Subject: Re: follow-up and background

We anticipate a respond by the end of next week before the comment period ends. We have confirmed that all anonymous comments are considered as credible.

Sent from my iPhone


Is there any more information, or perhaps draft language, I can ptovide to help you consider how best to proceed at this point?

-- Demetrios

This message is from a law firm and may contain information thqt is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply email that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for you;r cooperation. .

From: Kouzoukas, Demetrios

Sent: Thursday, July 22, 2010 2:01 PM

To: [email protected]; [email protected]; [email protected]

4


Subject: follow-up and background


Here is the article I referenced in my conversations with James and Leslye. If you are open to the procedure I discussed with Leslye -- whereby a commentercould:request that their identity not be released, I would be pleased to propose language that such corhmenters could use and on which basis CMS would then oblige the request. .


«File: Cancer Experts Threatened A ... pdf» ,

-- Demetrios


Covington & Burling LLP

1201 Pennsylvania Avenue, NW Washington, DC 20004-2401

http://www.cov.com/dkouzoukas/

[email protected]

Tel: 202.662.5057

Assistant: Dee Perkins (202.662.6003, [email protected]) . ,

Fax: 202.778.5057

download vcard: http://www.cov .comlbiographies/vcard.aspx? Attorney= 13540

This message is from a law firm and may contain information thal is confidential or legally privileged. Ifyou are not the intended recipient, please immedia(ely advise the sender by reply email that this message has been inadvertently transmitted to you; and delete this e-mail from your system. Thank you for your cooperation.

5



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 16,20103:20 PM To: McLeod, Donald E. (CMS/OEA) Cc: Rollins, James (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ) . Subject: RE: Provenge

Don, I think he misremembers his facts. Here's some background.

Prostate cancer is known to disproportionately affect black men. http://www.brostate-cancer.com/race-prostate

cancer.html

African-American Men and Prostate Cancer Black American men have the highest risk of prostate cancer in the United States. They also have the highest risk of developing aggressive prostate cancer and also have the highest prostate cancer mortality rates. African-American Men and Prostate Cancer Black American men have the highest risk of prostate cancer in the United States. They also have the highest risk of developing aggressive prostate cancer and also have the highest prostate cancer mortality rates.

There are two predominant theories as to why African-American men have a higher risk of prostate cancer: genetics and healthcare access. Some doctors believe that genetics play an important role; others believe that limited access to quality healthcare is to blame. A third theory exists: sor;ne doctors believe that a traditional diet which is high in saturated fat causes the higher prostate cancer risk. However, the diets of many Americans, regardless of race, have higher levels of fat than the diets of !men of any other nationality. Click to here to read more about prostate cancer risk in the United States.

The most widely-accepted theory of the black men's higher prostate cancer incidence and mortality rate melds the first and second theories. Genetics (due to melanin levels in the skin) may predispose African-American men, while limited access to quality healthcare does not catch the disease in earlier stages and does not get these men the best possible treatment.

From: McLeod, Donald E. (CMS/OEA) Sent: Monday, August 16, 2010 3:17 PM To: Jacques, Louis B. (CMS/OCSQ) Subject: FW: Provenge

Louis Could this be true?

From: John Sexton [mailto:[email protected]] Sent: Monday, August 16, 2010 3:08 PM To: McLeod, Donald E. (CMS/OEA) Subject: RE: Provenge

Yes, calling Provenge a drug is incorrect. It's a therapy.

1


I

I'll have a look at the NCO list. I did look at Abarelix and it was approved for all 'FDA approved uses. Only off-label uses were non-covered. But I guess it shows that a similar national decision was made. I'll continue to look into it.

Incidentally, there appears to be an error in this proposal: http://www.cms.gov/mcd/viewdraftdecisionmemo.asp?id=129

"Prostate cancer incidence rates are significantly higher in black men than in ~hite men."

I'm fairly certain the author has that reversed. From all I've been reading, pros,tate cancer incidence is always higher ih white men.

John

From: McLeod, Donald E. (CMS/OEA) [mailto:[email protected]] Sent: Monday, August 16, 2010 11:38 AM To: John Sexton Subject: Provenge

Here's a list of NCDs on cancer treatments. You'll have to read through them as well as any accompanying LeOs to figure out coverage conditions.

Abarelix for prostate cancer Stem cell transplant for multiple myeloma Blood brain barrier chemotherapy for brain tumors / Radioimmunotherapy for non Hodgkins lymphoma

The list of all NCDs is at http://www.cms.gov/mcd/index list.asp?list type=nca

It may be a bit disingenuous to simply call Provengea drug though, as it is not a drug in the usual sense, it is immunotherapy in which the patient's white blood cells are collected and then reintroduced to the patient's bloodstream. Part B drugs are infusion drugs.

2


~ollins, James (CMS/OCSQ)

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 23,20104:17 PM To: . Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: AUA

Just got off the phone with her. They are happy to participate in any manner, guest speaker, panelist etc. They have ialready prepared talking points for other insurers etc. Feel free to contact her directly. From our conversations to date our request is:

1. A guest panelist with a urologic oncology background; and , 2. An AUA presentation on how urologists determine hormonal failure and degree of symptomatology.

From: Stinchcomb, Stephanie [mailto:[email protected]] Sent: Monday, August 23, 2010 1:38 PM To: Jacques, Louis B. (CMSjOCSQ) Subject: RE: Contact info

I'm on a call at 3:30 pm but should be available any other time.

. Stephanie N. Stinchcomb, CPC, CCS-P, ACS-UR Manager of Reimbursement Regulation, Reimbursement & Quality American Urological Association 1000 Corporate Boulevard Linthicum, MD 21090 Toll Free 866-746-4282 Extension 3786 Direct Phone: 410 689 3786 Fax 410 689 3907

DISCLAIMER: Information or advice provided by the coding specialists at the American Urological Association (AUA) reflects a consensus of informed opinion regarding proper use of CPT codes. However, our comments are based on limited knowledg.e of the medical and factual circumstances of an individual case. This advice is for the use only of the person(s) addressed and may contain confidential or privileged information. Th~se materials may not be copied or disseminated without the express written consent of AUA.

Neither AUA nor its employees or representatives are qualified to make clinical judgments or to render legal advice regarding the proper code for any given procedure, nor the consequences of use of any code. For legal advice, recipients of such information should consult their own counsel.

'I From: Jacques, Louis B. (CMSjOCSQ) [mailto:[email protected]] Sent: Monday, August 23,2010 1:34 PM To: Stinchcomb, Stephanie Subject: RE: Contact info

On another call now, will try later

From: Stinchcomb, Stephanie [mailto:[email protected]] Sent: Monday, August 23, 2010 1:30 PM . To: Jacques, Louis B. (CMSjOCSQ) Subject: RE: Contact info

1


Yes I am.

Stephanie N. Stinchcomb, CPC, CCS-P, ACS-UR Manager of Reimbursement Regulation, Reimbursement & Quality American Urological Association 1000 Corporate Boulevard Linthi'Cum, MD 21090 Toll Free 866-746-4282 Extension 3786 Direct Phone: 4106893786 Fax 410 689 3907

DISCLAIMER: Information or advice provided by the coding specialists at the Pimerican Urological Association (AUA) reflects a consensus of informed opinion regarding proper use of CPT codes. Hbwever, our comments are based on limited knowledge of the medical and factual circumstances of an individual cas~. This advice is for the use only of the person(s) addressed and may contain confidential or privileged information. Th~se materials may not be copied or disseminated without the express written consent of AUA.

Neither AUA nor its employees or representatives are qualified to make clinical judgments or to render legal advice regarding the proper code for any given procedure, nor the consequences of use of any code. For legal advice, recipients of such information should consult their own counsel. .

From: Jacques, Louis B. (CMS/OCSQ) [mailto:[email protected]] Sent: Monday, August 23, 2010 1:05 PM To: Stinchcomb, Stephanie Subject: RE: Contact info

Are you free now?

I From: Stinchcomb, Stephanie [mailto:[email protected]] sent: Monday, August 23, 2010 1:04 PM To: Jacques, Louis B. (CMS/OCSQ)

I Subject: RE: Contact info

I Look forward to it.

Stephanie N. Stinchcomb, CPC, CCS-P, ACS-UR Manager of Reimbursement Regulation, Reimbursement & Quality American Urological Association 1000 Corporate Boulevard Linthicum, MD 21090 Toll Free 866-746-4282 Extension 3786 Direct Phone: 4106893786 Fax 4106893907

DISCLAIMER: Information or advice provided by the coding specialists at the American Urological Association (AU A) reflects a consensus of informed opinion regarding proper use of CPT codes. ~owever, our comments are based on limited knowledge of the medical and factual circumstances of an individual ca~e. This advice is for the use only of the person(s) addressed and may contain confidential or privileged ,information. Th'ese materials may not be copied or disseminated without the express written consent of AUA.

Neither AUA nor its employees or representatives are qualified to make clinical judgments or to render legal advice regarding the proper code for any given procedure, nor the consequences of use of any code. For legal advice, recipients of such information should consult their own counsel. .

2


From: Jacques, Louis B. (CMS/OCSQ) [mailto:[email protected]] Sent: Monday, August 23, 2010 12: 10 PM To: Stinchcomb, Stephanie Subject: RE: Contact info

We're looking for AUA input on a prostate cancer assessment and treatment iss;ue, possibly as a speaker for a public meeting. Will give you a call later this week.

From: Stinchcomb, Stephanie [mailto:[email protected]] Sent: Monday, August 23, 2010 11:48 AM To: Jacques,· Louis B. (CMS/OCSQ) Subject: RE: Contact info

Dr. Jacques,

I

I I am still here at the AUA. I look forward to hearing from you.

Stephanie N. Stinchcomb, CPC, CCS-P, ACS-UR Manager of Reimbursement Regulation, Reimbursement & Quality American Urological Association 1000 Corporate Boulevard

. Linthicum, MD 21090 • Toll Free 866-746-4282 Extension 3786 Direct Phone: 410 689 3786 Fax 410 689 3907

DISCLAIMER: Information or advice provided by the coding specialists at the American Urological Association (AUA) reflects a consensus of informed opinion regarding proper use of CPT codes. However, our comments are based on limited knowledge of the medical and factual circumstances of an individual case. This advice is for the use only of the person(s) addressed and may contain confidential or privileged information. These materials may not be copied or disseminated without the express written consent of AUA

Neither AUA nor its employees or representatives are qualified to make clinical j~dgments or to render legal advice regarding the proper code for any given procedure, nor the consequences of use of any code. For legal advice, reCipients of such information should consult their own counsel.

From: Jacques, Louis B. (CMS/OCSQ) [mailto:[email protected]] Sent: Monday, August 23,20108:56 AM To: Stinchcomb, Stephanie Subject: Contact info

Stephanie,

Just making sure your contact info is still current. My staff may be contacting AUA on a current issue. Thanks.

Louis

Louis B. Jacques, MD Director, Coverage & Analysis Group Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Mailstop C1-09-06 7500 Security Blvd

3


.~ ;

\

~altimore MD 21244 1

(410) 786-4512 ,I (410) 786-9286 (FAX) I

[email protected]

/

4



From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, August 25,20108:28 AM To: PASERCHIA,·LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ) . Subject: Provenge MEDCAC Questions v2 082410 doc revision 3.doc

: Attachments: Provenge MEDCAC Questions v2 082410 doc revision 3.doc

Attached please find the PROVENGE MEDCAC questions revised to reflect the discussion with Cliff and Saty. Eileen and I have both worked on this to be sure we addressed all comments. Please revielN and make changes in track changes so

I .the document may be finalized for Louis's review and then sent to Cliff and Saty.

Thanks,

Leslye

1


(b)(6)(b)(6) (b)(6)


Prostate Cancer. The datefor the ]}IF~DCAC to revie'w e'vidence concerning this ! issue is Jl7ednesday, Novernber 17, 2010from 7:80 arn to 4:30 prn EST. T'his : lneeting will b~ held at the CMSAuditoriurn inBalt~'more, Ma1:ylanri. Due to , your e.rpertise, .you are a j)otential candidate to serve fls a panelist.

The MEDCAC, in its present structure, includes botlf standing panel rnelnbers I and guestpanelrnembers. According to the [?ederaIAdvisory Cornrnittee Act I (FACAj, the ]Y11~DCAC is only alloLved to have fifteen lnernbers serve at alZY one

rneeting. T~lease advise the l{..I:ecutive Secretary, Maria F~llis at . [email protected] ?fyou are able to participqte. Due to [i'ACA

restraints on the ma.rirnurn nurnberqfpanelists, it is 'possible that not everyone ! who is available will be invited to partiClpate in this ifJanel. We 'will be . fz'nalzzing the roster short~y and will not{fj you withfn the next couple qfweeks.

We look.forward to hearing,from you. '

llcaltllhlsurancc .SjJcdaii5t Divisioll of" Opcrations alld In/()flllalioll Mana,gr:mcnt COVCTd!fC: ;JI1dAnaiysi5 Group, OC:S'Q (410) 786-030.9 .

[email protected]

2


I


From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, August 25, 201010:58 AM fo: Rollins, James (CMS/OCSQ) ~ubject: davenport provenge Ikf 082510.doc ~ttachments: davenport provenge Ikf 08251 O.doc

Jim:

The response to Ms. Davenport is attached. It contains language that Louis used. in previous responses to controlled inquiries. I will place the folder on your chair.

Leslye

1



From: Fitterman, Leslye (CMS/OCSO) I Sent: Wednesday, August 25,201012:53 PM iTo: Rollins, James (CMS/OCSO) iiSubject: RE: davenport provenge Ikf 082510.doc

:You are welcome

From: Rollins, James (CMSjOCSQ) Sent: Wednesday, August 25, 2010 12:53 PM

, To: Fitterman, Leslye (CMSjOCSQ)

'; Subject: RE: davenport provenge Ikf 082510.doc

Thanks, I'll forward to Louis. Jarollins

i From: Fitterman, Leslye I Sent: Wednesday, August 25, 2010 10:58 AM To: Rollins, James (CMSjOCSQ) Subject: davenport provenge Ikf 082510.doc

Jim:

; The response to Ms. Davenport is attached. It contains language that Louis used in previous responses to controlled : inquiries. I will place the folder on your chair.

, Leslye

1


(b)(6) (b)(6)


w~label use C!fAutologous Cellular bnlnunothera1~Y Treat1nent C[f.L~etastatic Prostate Cancer to our Medicare Evidence Developrn~nt (5 Coverage Advisory C01nlnittee (Ml~l)CAC). The panel will discuss the sl(jJi"ciency ifcurrently kl'vailable evidence regarding the clinical ben~fits and /zanns ifon-Iabel and W:" 'label use ifAutologous Cellular lrntnunotherapy Trea'l1nent r/'Metastatic fJrostate Cancer. The date.fbr the lv[l~l)CAC to revie,w evidence concerning this issue is Wednesday, Novernber 17, 201 O,frorn 7:80 a1n to 4:80 j)fn I~ST. This inueting 'will be held at the CMS Auditoriurn in BaltiJnore, Maryland. Due to !your expertise, you are a potential candidate toserve a;)' a panelist.

The l\![E~DCAC, in itspresent structure, includes both!standingpanel rnembers and guest panel rnem1)ers. According to thep-'ederal Advisory Corn/nittee Act (FACA), the Ml~l)CAC is on?y allozved to havejifteerl m,embers serve at anyone .rneeting.. ])lease advise the B~xecutive Secretary, Maria E~llis at :[email protected] if~YoU are able to participate. Due to Ji~CA ; restraints on the rna.x'irrz,uln nuntber ifpanelist~, it is possible that not everyone .'who is available will be invited to jHlrticzjJate in this jJanel. IfTe 'will be ji"nalizing the roster ,"hortly and will notifY you zvithin the next couple ifweeks. ·We look,jbrward to Izearing,frorn you.

i Healtl11nsurance Sped:J1i'it j Division ofOperatiom and Illlhrmation Mimagcmcllt . Coverage andAnaly.."}:,, Grollp, OG5Q

(410) 786~03o.9

. [email protected]

2


Rollins, James (CMS/OCSQ) Il

From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, August 26,20107:21 AM Iro: Rollins, James (CMS/OCSQ); AShby, Lori M. (CMS/OjCSQ) ~ubject: FW: Letter from Senators Spector and Kerry , Attachments: cms-senators-spector-kerry.gif .

While I can compose a response, should we hold it until the letter comes throug~ OSORA? I

From: steven wilson [mailto:[email protected]] ISent: Wednesday, August 25, 2010 6:25 PM !~o: Fitterman, Leslye (CMS/OCSQ) Subject: Letter from Senators Spector and Kerry·

iPlease publicly answer the attached letter from Senators Spector and Kerry in a timely fashion. I . .

;Regards, Dr SG Wilson

1


litollins. James (CMS/OCSQ)

From: Ashby, Lori M. (CMS/OCSQ) Sent: Thursday, August 26,20107:27 AM ,

"To: Fitterman, Leslye (CMS/OCSQ);,Roliins, James (CMS/OCSQ) $ubject: RE: Letter from Senators Spector and Kerry ,

Yes. Thanks. ; . .,

~ori M. Ashby

Special Assistant OCSQ/Coverage and Analysis Group 4107866322 [email protected]

Notice: The contents of this messag~ and any attachments may be privileged and confidel~tial. Please do not disseminate without the ~pp:i:()val of the Centers for !v1celicare &: Medicaid Services. If y\lU are not an intended rec}pient, or have received thi~ message in pTor, please delete it without reading it and please do not print, copy, forward, disseminate, or otherwise use theinIormation. Also, blease notify the sender that you have received this cOlmnunication in error. Your receipt bE this message is not intended to waive any ilPplicable privilege.

I

From: Fitterman, Leslye (CMSjOCSQ)

,ISent: Thursday, -August 26, 2010 7:21 AM [To: Rollins, James (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ) ~ubject: FW: Letter from Senators Spector and Kerry

While I can compose a response, should we hold it until the letter comes througl;l OSORA?

steveh wilson [mailto:[email protected]] Wednesday, August 25, 2010 6:25 PM

iJ'0: Fitterman, Leslye (CMSjOCSQ) i!Subject: Letter from Senators Spector and Kerry

'Please publicly answer the attached letter from Senators Spector .and KerI)' in a timely fashion.

Regards, Dr SG Wilson

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, August 26, 2010 8: 19 AM To: Rollins, James (CMS/OCSQ); Ashby, LoriM. (CMS/OCSQ) Subject: DiBenedetto Ikf 082610.doc Attachments: DiBenedetto Ikf 082610.doc

Attached is the response to an email sent to Don Berwick regarding the PROVENGE NCA. I have used language that louis has used in previous responses. I will give the folder to Jim.

Thanks,

leslye

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, August 26,20109:12 AM To: Rollins, James (CMS/OCSQ) Subject: RE: davenport provenge Ikf 082510.doc

Looks fine

From: Rollins, James (CMSjOCSQ) Sent: Wednesday, August 25,2010 12:56 PM To: Jacques, Louis B. (CMSjOCSQ) Subject: FW: davenport provenge Ikf 082510.doc

Louis, here is the response to a letter from Dr. Davidson, an oncologist who is asking that we allow patients to have access to provenge, and "not impede access to this new innovative therapy." Leslye's response was crafted from some of the responses we sent out. Jarollins

From: Fitterman, Leslye (CMSjOCSQ) Sent: Wednesday, August 25, 2010 10:58 AM To: Rollins, James (CMSjOCSQ) Subject: davenport provenge Ikf 082510.doc

Jim:

The response to Ms. Davenport is attached. It contains language that Louis used in previous responses to controlled inquiries. I will place the folder on your chair..

Leslye

1


Rollins, James (CMSIOCSQ)

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, August 26, 2010 9: 13 AM To: Rollins, James (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) Subject: RE: DiBenedetto Ikf 08261 O.doc

Looks fine

From: Rollins, James (CMSjOCSQ) Sent: Thursday, August 26, 2010 8:58 AM To: Jacques, Louis B. (CMSjOCSQ) Cc: Fitterman, Leslye (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ) Subject: FW: DiBenedetto Ikf 082610.doc

, Louis, here is another response created by Lesley addressing concerns by Dr. Joseph DiBendedtto. He addressed the letter to Dr. Berwick, and complains that Medicare is denying provenge, and saying that NCA would take too long and delay treatment for patients with prostate cancer. I will drop off the incoming. Jarollins

From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, August 26,20108:19 AM To: Rollins, James (CMSjOCSQ); Ashby, Lori M. (CMS/OCSQ) Subject: DiBenedetto Ikf 082610.doc

Attached is the response to an email sent to Don Berwick regarding the PROVENGE NCA. I have used language that Louis has used in previous responses. I will give the folder to Jim.

Thanks,

leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, August 26,2010 1:19PM To: Jacques, Louis B. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Graves, Patricia A.

(CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John' (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)

Subject: PROVENGE MEDCAC Announcement & update to tracking sheet Attachments: Announcement of meeting date 082610 V2.docx

Louis:

For web clearance to be posted next week.

Thanks

1



From: Dolina, Elaine L (CMS/OCSQ) Sent: Monday, August 30, 2010 8:24 AM To: Jacques, Louis s: (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A.

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Manlove, John (CMS/OCSQ) Subject: RE: Announcement of meeting date 08261 O.docx .

The link will be http://www.cms.gov/mcd/viewmcac.asp?where=index&mid=56

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, August 26, 2010 10:56 AM To: Rollins, James (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Manlove, John (CMS/OCSQ) Subject: RE: Announcement of meeting date 082610.docx

Needs correct link for the November MEDCAC.

In order to do that, we need a MEDCAC announcement (separate task than this tracking sheet), specifically summarizing the MEDCAC, which also needs to be posted. Please see other 2010 MEDCAC announcements for template.

From: Rollins, James (CMS/OCSQ) Sent: Thursday, August 26, 2010 10:50 AM To: Jacques, Louis B. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ) Subject: FW: Announcement of meeting date 082610.docx

Louis, here is the update posting for the tracking sheet announcing the upcoming meeting of the MEDCAC on provenge. Needs to be web-cleared. Jarollins

From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, August 26, 2010 10:38 AM To: Rollins, James (CMS/OCSQ) Cc: Caplan, Stuart (CMS/OCSQ) Subject: FW: Announcement of meeting date 082610.docx

Jim:

According to the IIlnternet Posting SOP" document distributed at the staff meeting yesterday, you need to clear this posting to update the tracking sheet and the MEDCAC meeting section on the coverage website.

Thanks, Leslye

TO BE SENT TO JOHN MANLOVE

John,

Attached is the announcement for the MEDCAC to be held on November 17, 2010. This should be placed under the

MEDCAC folder on the CAG website. Also please! update the NCA tracking sheet for Autologous Cellular Immunotherapy Treatment of M.etastatic Prostate Cancer under ACTIONS TAKEN with:

1


August 26, 2010 Date of Medicare Evidence Development Advisory Committee (MEDCAC) Announced (add a link to the MEDCAC announcement)

Please note that I have placed a comment in the announcement to update the link to register for the meeting.

Thanks in advance!

Leslye

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, August 30,20109:09 AM To: Rollins, James (CMS/OCSQ) Subject: FW: PROVENGE MedCAC &AUA

FYI

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, August 30, 20108:59 AM To: Fitterman, Leslye (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ) Subject: RE: PROVENGE MedCAC & AUA

OK, Good job, thanks. Sounds like a plan.

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, August 30, 2010 8:40 AM To: Jacques, Louis B. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ) Subject: PROVENGE MedCAC &AUA

Louis: Lori and I talked with the representatives from A UA on Friday afternoon. There suggestion for a presenter of "late stage prostate ~ancer 101" (e.g., how assess symptoms related to cancer, treatment options, etc.) was David F. Penson, M.D., who was an investigator in the IMPACT trial. We suggested that they find someone who is a thought leader that was not associated with any of . the PROVENGE trials. They will send us a list of other experts to present early this week. In addition, we asked ~lbout Dr. Patrick Walsh (JHH) for another role in the MedCAC and were assured that he is a renowned thought leader.

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, August 31,20109:55 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Jacques, Louis B.

(CMS/OCSQ) I

Subject: Provenge MEDCAC Questions v2 082410 doc revision 3.doc Attachments: Provenge MEDCAC Questions v2 082410 doc revision 3.doc·

Jim:

Attached please find the MedCAC questions as revised with the input of Saty and Cliff. Are they ready for Maria to send to Saty and Cliff for their review of this version.

Leslye

1



From: Rollins, James (CMS/OCSQ) Sent: Tuesday, August 31,201010:47 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Jacques, Louis B.

(CMS/OCSQ) Subject: RE: Provenge MEDCAC Questions v2 082410 doc revision 3.doc

Yes, lets forward them to Maria for her to send them to Saty and Cliff for a final review. Jarollins

From: Fitterman, Leslye (CMSjOCSQ) Sent: Tuesday, August 31, 2010 9:55 AM To: Rollins, James (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ)i Pencek, Eileen (CMSjOCSQ)i Jacques, Louis B. (CMSjOCSQ) Subject: Provenge MEDCAC Questions v2 082410 doc revision 3.doc

Jim:

Attached please find the MedCAC questions as revised with the input of Saty and Cliff. Are they ready for Maria to send to Saty and Cliff for their review of this version.

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, August 31,201010:58 AM To: Ellis, Maria A (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A

(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: PROVENGE MEDCAC Questions Attachments: Provenge MEDCAC Questions v2 082410 doc revision 3.doc

Marie: .

Attached please find the MEDCAC questions for the November 17, 2010 meeting on PROVENGE. The questions have been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for

. their review.

Thanks for your assistance.

Leslye

1



From: Berliner, Elise (AHRQ) Sent: Tuesday, August 31,201011 :31 AM To: Fitterman, Leslye (CI\IIS/OCSQ); Rollins, James (CMS/OCSQ) Subject: . FW: Provenge project

Conference call Thursday morning

10: 30 a.m. eastern time

(877) 287-0283 / Host code (Naomi) 899202 I Participant code: 831721

Below is the email trail. The issue is how to deal with the issues of the effects of leukophoresis in the control group and the use of the frozen cells in the cross overs. This has been raised many times in the discourse on the topic. A full systematic review on leukophoresis is outside the scope of the project.

Below are my suggestions, todo a critical appraisal on specific information on the provenge process. If you look at the publicly available FDA documents below, a lot of the information has been redacted, so even if you did a systematic review on leukophoresis, the actual techniques for Provenge are proprietary, so we could not conclusively determine generalizability.

From: Berliner, Elise (AHRQ) Sent: Monday, August 30,20105:54 PM To: Aronson, Naomi; Mark, David; Sarsany, Lisa; DeliaFave, Kimberly Subject: RE: Provenge project

Thursday morning is the best for me. I will also check with CMS.

I found this other document on the FDA website: http://www.fda. gov/down 10ads/BioiogicsBIoodVaccines/CeiluiarGene TherapyProd uctsl Approved Products/UCM213 796. pdf

It states that about 30% of patients needed more than 3 apheresis. What about the control patients? Was the quality checked and were there APH failures .in the control patients? Is there any published data on the number of cells harvested in active vs. control patients (which as they state in this document might be relevant to patient health status).

From: Aronson, Naomi [mailto:[email protected]] Sent: Monday, August 30,20105:17 PM To: Berliner, Elise (AHRQ); Mark, David; Sarsany, Lisa; DeliaFave, Kimberly Subject: RE: Provenge project Importance: High

Kim will coordinate a teleconference to speak ASAP. Wed or Thurs jf possible. Plan on half an hour.

From: Berlin~r, Elise (AHRQ) [mallto:[email protected]] Sent: Monday, August 30, 2010 4:08 PM To: Mark, David; Aronson, Naomi; Sarsany, Lisa Subject: RE: Provenge project

When is a good time for you to talk? I think it would be good to have CMS on the phone too.

1


As I mentioned in previous emails, we do not expect you to do a review of adjunct issues such as the adverse effects of leukopheresis.

But we need you to do a critical appraisal of all available information. So for example, looking at this document from the FDA: http://www.fda.gov/downloads/Biolog ics BloodVaccines/CellularGene TherapyProd uctsl Approved Prod ucts/UCM213114. pdf

It says that if a lot fails to meet requirements for quality, another leukophoresis is required. How often did this happen in the trials? Is there a relationship between outcomes and number of leukopheresis?

It says that each lot is shipped fresh without cryopreservation. Why? Is there any evidence that cryopreservation leads to adverse events? (relevant to the frozen cell cross overs).

It also says that the product has high inherent variability due to the autologous nature of the product. What are the parameters of the variability? What is the relationship of the number of cells harvested to outcome?

Etc. I think if you can layout the issues, ask the questions, and match any evidence to answer the questions, that would be a good approach. It is likely that there are no published answers to these questions, but that is OK too. You should provide a judgment on the strength of evidence for each question.

Does this help?

Elise

From: Mark, David [mailto:[email protected]] Sent: Monday, August 30, 2010 4:42 PM To: Berliner, Elise (AHRQ); Aronson, Naomi; Sarsany, Lisa Subject: Provenge project

Elise,

Naomi and I would like to discuss some issues that are arising as we review some of the materials you supplied and the public comments materials. There are concerns about the scope of the report, since some of these issues would require an adjunct systematic review to explore in any depth. For example, to address the issues raised in this attached summary of a critique would require a systematic review of effects of adverse effects of leukopheresis, possibly a review of aging immunology, and a review of the natural history of prostate cancer at this particular stage. I believe these reviews would not prove to be conclusively applicable to theProvenge clinical trials. Perhaps they can be touched on in a discussion section. We would like to discuss a reasonable approach to these issues. There are possibly other issues too, that do not relate to the "internal validity" of the provenge trials but "external validity." Another such issue that comes to mind is the effect of frozen provenge cross-over treatment.

Regards,

David H. Mark MD MPH TEG Scientist

2



From: Berliner, Elise (AHRQ) Sent: Tuesday, August 31, 2010 11 :32 AM To: 'DellaFave, Kimberly' Cc: Fitt~rman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: FW: Provenge project

Kim,

I fowarded the information below, but Leslye and Jim are copied on this message if you want to send them more info or the meeting request.

Thanks, Elise

From: Berliner, Elise (AHRQ) Sent: Tuesday, August 31,2010 11:31 AM To: Fitterman, Leslye (CMS/OCSQ)i Rollins, James (CMS/OCSQ) Subject: FW: Provenge project



(877) 287.0283 I Host code (Naomi) 899202 I Participant code: 831721

Below is the email trail. The issue is how to deal with the issues of the effects of leukophoresis in the control group and the use of the frozen cells in the cross overs. Th~s has been raised many times in the discourse on the topic. A full systematic review on leukophoresis is outside the scope of the project.


From: Berliner, Elise (AHRQ) Sent: Monday, August 30, 2010 5:54 PM To: Aronson, Naomii Mark, David; Sarsany, Lisa; DeliaFave, Kimberly Subject: RE: Provenge project

Thursday morning is the best for me. I will also check withCMS.

I found this other document on the FDA website: , http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM213796.pdf

It states that about 30% of patients needed more than 3 apheresis. What about the control patients? Was the quality checked and were there APH failures in the control patients? Is there any published data on the number of cells harvested in active vs. control patients (which as they state in this document might be relevant to patient health status).

1


From: Aronson, Naomi [mailto:[email protected]] Sent: Monday, August 30, 2010 5:17 PM To: Berliner, Elise (AHRQ); Mark, David; Sarsany, Lisa; DeliaFave, Kimberly Subject: RE: Provenge project . Importance: High

Kim will coordinate a teleconference to speak ASAP. Wed or Thurs if possible. Plan on half an hour.

From: Berliner, Elise (AHRQ) [mailto:[email protected]] Sent: Monday, August 30, 20104:08 PM To: Mark, David; Aronson, Naomi; Sarsany, Lisa Subject: RE: Provenge project


As I mentioned in previous emails, we do not expect you to do a review of adjunct issues such as the adverse effects of leukopheresis.

But we need you to do a critical appraisal of all available information. So for example, looking at this document from the FDA: http://www. fda.gov/downloads/Biolog icsBloodVaccines/CeliularGene TherapyProductsl Approved Products/UCM213114. pdf

It says that if a lot fails to meet requirements for quality, another leukophoresis is required. How often did this happen in the trials? Is there a relationship between outcomes and number of leukopheresis?



Etc. I think if you can layout the issues, ask the questions, and match any evidence to answer the questions, that would be a good approach. It is likely that there are no published answers to these questions, but that is OK too. You should provide a judgment on the strength of evidence for each question.

Does this help?

Elise


Elise,

Naomi and I would like to discuss some issues that are arising as we review some of the materials you supplied and the public comments materials. There are concerns about the scope of the report, since some of these issues would require an adjunct systematic review to explore in any depth. For example, to address the issues raised in this attached summary of a critique would require a systematic review of effects of adverse effects of leukopheresis, possibly a review of aging immunology, and a review of the natural history of prostate cancer at this particular stage. I believe these reviews would not prove to be conclusively applicable to the Provenge clinical trials. Perhaps they can be touched on in a discussion section. We would like to discuss a reasonable approach to these issues. There are possibly other issues too, that do not relate to the "internal validity" of the provenge trials but "external validity." Another such issue that comes to mind is the effect of frozen provenge cross-over treatment.

2


Regards,

David H. Mark MD MPH TEe Scientist

3



From: Berliner, Elise (AHRQ) Sent: Tuesday, August 31, 2010 11 :32 AM To: 'DeliaFave, Kimberly' Cc: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: FW: Provenge project

Kim,

I fowarded the information below, but Leslye and Jim are copied on this message if you want to send them more info or the meeting request.

Thanks, Elise

From: Berliner, Elise (AHRQ) Sent: Tuesday, August 31, 2010 11:31 AM To: Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: FW: Provenge project



(877) 287-0283 I Host code (Naomi) 899202 I Participant code: 831721

Below is the email trail. The issue is how to deal with the issues of the effects of leukophoresis in the control group and the use of the frozen cells in the cross overs. This has been raised many times in the discourse on the topic. A full systematic review on leukophoresis is outside the scope of the project.


------------------------~~--------From: Berliner, Elise (AHRQ) Sent: Monday, August 30, 2010 5:54 PM To: Aronson, Naomi; Mark, David; Sarsany, Lisa; DeliaFave, Kimberly Subject: RE: Provenge project

Thursday morning is the best for me. I will also check with CMS.

I found this other document on the FDA website: http://www. fda. gov/downloads/Biolog icsBloodVacci nes/CellularGene TherapyProductsl Approved Products/U CM213796. pdf

It states that about 30% of patients needed more than 3 apheresis. What about the control patients? Was the quality checked and were there APH failures in the control patients? Is there any published data on the number of cells harvested in active vs. control patients (which as they state in this document might be relevant to patient health status).

1


From: Aronson, Naomi [mailto:[email protected]] Sent: Monday, August 30, 2010 5:17 PM To: Berliner, Elise (AHRQ); Mark, David; Sarsany, Lisa; DellaFave, Kimberly Subject: RE: Provenge project Importance: High

Kim will coordinate a teleconference to speak ASAP. Wed or Thurs if possible. Plan on half an hour.

From: Berliner, Elise (AHRQ) [mailto:[email protected]] Sent: Monday, August 30, 2010 4:08 PM To: Mark, David; Aronson, Naomi; Sarsany, Lisa Subject: RE: Provenge project


As I mentioned in previous emails, we do not expect you to do a review of adjunct issues such as the adverse effects of leu kopheresis.

But we need you to do a critical appraisal of all available Information. So for example, looking at this document from the' FDA: . http://www.fda. gov/downloads/BiologicsB 100dVaccines/Cellula rGene Thera pyProducts/Approved Prod ucts/UCM213114. pdf

Itsays that if a lot fails to meet requirements for quality, another leukophoresis is required. How often did this happen in the trials? Is there a relationship between outcomes and number of leukopheresis?



Etc. I think if you can layout the issues, ask the questions, and match any evidence to answer the questions, that would be a good approach. It is likely that there are no published answers to these questions, butthat is OK too. You should provide a judgment on the strength of evidence for each question.

Does this help?

Elise


Elise,

Naomi and I would like to discuss some issues that are ariSing as we review some of the materials you supplied and the public comments materials. There are concerns about the scope of the report, since some of these issues would require an adjunct systematic review to explore in any depth. For example, to address the issues raised in this attached summary of a critique would require a systematic review of effects of adverse effects of leukopheresis, possibly a review of aging immunology, and a review of the natural history of prostate cancer at this particular stage. I believe these reviews would not prove to be conclusively applicable to the Provenge clinical trials. Perhaps they can be touched on in a discussion section. We would like to discuss a reasonable approach to these issues. There are possibly other issues too, that do not relate to the "internal validity" of the provenge trials but "external validity." Another such issue that comes to mind is the effect of frozen provenge cross-over treatment.

2


Regards,

David H. Mark MD MPH TEe Scientist

3



From: Rollins, James (CMS/OCSQ) Sent: Tuesday, August31,2010 11:37 AM To: 'DeliaFave, Kimberly' Subject: Accepted: Updated: Provenge Project Teleconference

1



From: Dolina, Elaine L. (CMS/OCSQ) Sent: Tuesday, August 31, 20104:08 PM To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye(CMS/OCSQ); Rollins, James

(CMS/OCSQ); PASEHCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: Announcement of meeting date 082610 V2 Ibj.docx

Posted!

http://www.cms.gov/mcd/viewtrackingsheet.asp?id=247 http://www.cms.gov/mcd/viewmcac.asp?where=index&mid=56

-----Original Message----From: Jacques, Louis B. (CMS/OCSQ) Sent: Tue 8/31/2010 10:19 AM To: Dolina, Elaine L. (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j Rollins, James (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: Announcement of meeting date 082610 V2 lbj.docx

Ok to post after 4 PM today

From: Dolina, Elaine L. (CMS/OCSQ) Sent: Tuesday, August 31, 2010 10:18 AM To: Jacques, Louis B. (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j Rollins, James (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: Announcement of meeting date 0826H~ V2 lbj. docx

Small change made per Louis.

From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, August 31, 2010 9:57 AM To: Dolina, Elaine L. (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: Announcement of meeting date 082610 V2 lbj.docx

Elaine,

Please translate this. I'd like to take a final look before we post. Thanks.

1


Louis

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, August 39, 2919 9:55 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. {CMS/OCSQ) Subject: Announcement of meeting date 982619 V2 lbj.docx

Leslye,

I made some changes to the first parts. I should really be getting these through Jim, as that is the check that the DO has approved. If there are issues in that regard, Tamara or I are happy to discuss.

Louis

2


Rollins, James (eMS/OeSQ)

From: Pencek, Eileen (CMS/OCSQ) Sent: Tuesday, August 31,20105:53 PM _ To: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Team, I have questions/concerns about questionSc. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, August 31, 2010 10:58 AM To: Ellis, Maria A. (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek,Eileen (CMS/OCSQ) Subject: PROVENGE MEDCAC Questions

Marie:

Attached please find the MEDCAC questions for the November 17,2010 meeting on PROVENGE. The questions have been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for their review.


Leslye

1



From: Fitterman, Leslye (CIIIIS/OCSQ) Sent: Tuesday, August 31,20108:40 PM To: Pencek, Eileen (CMS/OCSQ) Cc: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: Re: PROVENGE MEDCAC Questions

Let's talk in the morning.

Sent from my iPhone

On Aug 31, 2010, at 5:53 PM, "Pencek, Eileen (CMS/OCSQ)" <[email protected]> wrote:

Team,

I have questions/concerns about question 5c.

Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, August 31, 2010 10:58 AM To: Ellis, Maria A. (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: PROVENGE MEDCAC Questions

Marie:

Attached please find the MEDCAC questions for the November 17,2010 meeting on PROVENGE. The questions have been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for their review.


Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, September 01,20108:10 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James

(CMS/OCSQ) Subject: FW: 2nd Request - Upcoming November 17,2010 MEDCAC Meeting Participation Invite

A no from Steve Teutsch.

From: Ellis, Maria A. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 8:03 AM To: Fitterman, Leslye (CMS/OCSQ) Subject: FW: 2nd Request - Upcoming November 17, 2010 MEDCAC Meeting Participation Invite

Good J.~orning!

See entail below.

Ilealt}1 hlSlJIal1Ce Specialist Division ofOperations iwd Ink)rmatjonManagcment Coverage andAnalysi~' Group, OCS'Q (410) 786-030.9

[email protected]

From: Steven Teutsch [mailto:[email protected]] Sent: Tuesday, August 31, 20104:57 PM To: Ellis, Maria A. (CMS/OCSQ) Subject: Re: 2nd Request - Upcoming November 17, 2010 MEDCAC Meeting Participation Invite

Hi, Maria-

Sorry I've been so slow in responding. I'm much more knowledgable about other topics (especially clinical preventive services,genomics), that don't think I would add much to this conversation. Trust you have better candidates than me!

Steve

Steven Teutsch, MD, MPH Chief Science Officer Los Angeles County Department of Public Health 313 N Figueroa St. Rm 708 Los Angeles. CA 90012 (213) 240-8189 [email protected]

213 481-2739 (fax)

> > > "Ellis, Maria A. (CMS/OCSQ)" < [email protected]> 8/31/2010 12:18 PM > > >

1


Good Morning!

The Coverage and Ana(ysis Group at the Centersfor l'\1edicare & Medicaid Services (CMS) is r~ferring the issue, clinical ben~fl"ts and harrns qfon-label and rdJ-label use qj'Autologous Cellular Irntnunotlzerap'.Y Treatnunt if Metastatic l)rostate Cancer to our ]\![edicare l~vidence Developtnent & CoverageAdviso~y Cornrnittee (lYfEDCACJ. The j)anel'will discuss the sufficiency Cf.fcurrent(y available evidence regarding the clinical benifi"ts and harms qfon-label and Cf.ff:"label use C!fAutologo us Cellular Imrnunotherapy Treatm,ent cif'lYletastatic ])rostaie Cancer. The date for the 1v[J1=DCAC to revie'w evidence concerning this issue is J/f7ednesday, Novernber 17, 2010frorn 7:80 am to 4:80 prn If.S1---. This rneeting will be held at the C-,-~SAuditoriurn in Baltimore, Maryland, Due to your expertise, you are a potential candidate to serve as a panelist.

T he Ml~DCAC, in its present structure, includes both standing panel mefnbers and guest panel rnernbers. ~4ccording to the [?ederal Advis(ny Cornrnittee Act (FfiCA), the Mlf.DCAC is only allowed to haveJifleen rnembers serve at any one rneeting. Please advise theF~.xecutive Secretal:y, Maria l~llis at [email protected] if:you are able to particzj)ate.Due to'FACA restraints on the rna.xirnurn nurnber ifpanelist~~ it ispossible that not e'veryone who is available 'will be invited to participate in this panel. We will be finalizing the roster shortly and 'will notri)! you '[uithin the luxt couple qj'weeks. We lookforward to hearing.from you.

flea/Ill Insurance ,S'pcciaii51 Divi;;ioIl ofOpera/ions aIld hJiiH7T1atioIl Management C'ovcra,ge aIld Ana/y:5is (lroup~ OCSQ

. (410) 786-0309

[email protected]

2



From: Pencek, Eileen (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9: 19 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Agree!

Eileen

From: Fitterman, Leslye (CMSjOCSQ) Sent: Wednesday, September 01, 2010 9: 11 AM To: Pencek, Eileen (CMSjOCSQ) SUbject:FW: PROVENGE MEDCAC Questions.

FYI

From: PASERCHIA, LORI A. (CMSjOCSQ) Sent: Wednesday, September 01, 2010 9:05 AM To: Fitterman, Leslye (CMSjOCSQ) Subject: RE: PROVENGE MEDCAC Questions

question Sc currently reads:

Patients who have metastatic disease castrate-resistant prostate cancer (i.e., have not failed hormonal therapy?

I suggest we change it to say:

Patients who have metastatic disease but'~~lmpt castrate-resistant prostate cancer (i.e., have not failed . '" ,,' ... _~Bif_d_':¥""'_,_,,!,_~

hormonal therapy~?

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 41 1

From: Fitterman, Leslye (CMSjOCSQ) Sent: Tuesday, August 31, 2010 10:58 AM To: Ellis, Maria A. (CMSjOCSQ) Cc: Atkinson, Michelle L. (CMSjOCSQ); Rollins, James (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ) Subject: PROVENGE MEDCAC Questions

Marie:

Attached please find the MEDCAC questions for the November 17,2010 meeting on PROVENGE. The questions have

been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for their review.

1



Leslye

2



From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9:22 AM To: Pencek, Eileen (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Actually, after looking at what I suggested, I recommend further revision:

Patients who have metastatic disease bui"a,~!p~ castrate-resistant prOstate cancer (i.e., have not failed hormonal therapy)?

Sorry 'bout that!

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 41 15

From: Pencek, Eileen (CMSjOCSQ) Sent: Wednesday, September 01,2010 9:19 AM To: Fitterman, Leslye (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: PROVENGE MEDCAC Questions

Agree!

Eileen

From: Fitterman, Leslye (CMSjOCSQ) Sent: Wednesday, September 01, 20109:11 AM

. To: Pencek, Eileen (CMSjOCSQ) Subject: FW: PROVENGE MEDCAC Questions

FYI

From: PASERCHIA, LORI A. (CMSjOCSQ) Sent: Wednesday, September 01, 20109:05 AIV1 To: Fitterman, Leslye (CMSjOCSQ) Subject: RE: PROVENGE MEDCAC Questions

question 5c currently reads:

Patients who have metastatic dise'ase castrate-resistant prostate cancer (i.e., have not failed hormonal therapy?


Patients who have metastatic diseasellli~@t~,r!i,ll castrate-resistant prostate cancer (i.e., have not failed hormonal therapyl?

1


Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 410.786.2115


Marie:

Attached please find the MEDCAC questions for the November 17, 2010 meeting on PROVENGE. The questions have

been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for

their review.


Leslye

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, September 01,20109:50 AM To: Rollins, James (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Thanks - I had to read it twice as well.

From: Rollins, James (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9:44 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

I think that the later one looks fine. I'm sure that the MEDCAC group can understand the question, though I had to read it twice before I understood it. Jarollins

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9:22 AM To: Pencek, Eileen (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Actually, after looking at what I suggested, I recommend further revision:

Patients who have metastatic Elisease-~~faJ:~:Q]ri~ castrate-resistant prostate cancer (i.e., have not failed hormonal therapV¥? .

Sorry 'bout that!


From: Pencek, Eileen (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9: 19 A~1

To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions

Agree! Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, September 01, 2010 9: 11 AM To: Pencek, Eileen (CMS/OCSQ) Subject: FW: PROVENGE MEDCAC Questions

FYI

1


From: PASERCHIA, LORI A. (CMSjOCSQ) Sent: Wednesday, September 01,2010 9:05 AM To: Fitterman, Leslye (CMSjOCSQ) Subject: RE: PROVENGE MEDCAC Questions

question Sc currently reads:

Patients who have metastatic disease castrate-resistant prostate cancer (i.e., have not failed hormonal therapy?


,~>Tf:C'F" S-', ,f:i7imF;'f6;;

Patients who have metastatic disease I)'~Jt[~,I~~l castrate-resistant prostate cancer (i.e., have not failed hormonal therapy~? .



Marie:

Attached please find the MEDCAC questions for the November 17, 2010 meeting on PROVENGE. The questions have

been revised by the team after the conversation with Saty and Cliff. This updated version of the questions are ready for their review.


Leslye

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, September 01, 2010 1:12 PM To: Brocato-Simons, Patricia M. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Belle, Wanda M. (CMS/OCSQ) Subject: Re: There is a HCPCS "C"code for Provenge, currently published

Thanks Patti. You will be in the loop.

Sent from my iPhone

On Sep 1,2010, at 12:22 PM, "Brocato-Simons, Patricia M. (CMS/OCSQ)" <[email protected]> wrote:

Leslye: approval of the drug, and of which I am one of the from program

collaboration with the Workgroup, IL::nAIn". GUbreath

have no

office.

This is me me ~oop

our delibet'ations on as we move forward case our decision would change the breadth of proposed coverage include a physician office I to the for new CCJIU\!;':!:.

need to tee that

From: Brocato-Simons, Patricia M. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 11:05 AM To: Hake, Cynthia S. (CMS/CMM); Eggleston, Felicia Y. (CMS/CMM); Fagan, Ann B. (CMS/CMM); MasonWonsley, Marsha M. (CMS/CMM); Brooks, Gaysha M. (CMS/CMM); Motsiopoulos, Diana S. (CMS/CMM) . Cc: Graves, Patricia A. (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Belle, Wanda M. (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: RE: There is a HCPCS "C" code for Provenge, currently published

Cindy, code a MEDCAC technology sse!~srne~n1: are planned as part of our

1


with 1,ei2m5Q~U on Olr

along with proposed fonowed by final m.....,nn on or alround

6/30/11

From: Jacques, Louis B. (CMSjOCSQ) Sent: Wednesday, August 04, 2010 11:36 AM . To: Brocato-Simons, Patricia M. (CMSjOCSQ); Belle, Wanda M. (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Rollins, James (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ) Cc: Graves, Patricia A. (CMSjOCSQ) Subject: FW: There is a HCPCS "C" code for Provenge, currently published

FYI

From: Hake, Cynthia S. (CMSjCMM) Sent: Wednesday, August 04, 2010 11:33 AM To: Jacques, Louis B. (CMSjOCSQ) Subject: There is a HCPCS "c" code for Provenge, currently published

Established by HAPG - outside the workgroup process - for use in HOPPS. As you can see by John's note below, we will likely establish a code in January for use is doctor's office.

From: Warren, John F. (CMSjCMM) Sent: Wednesday, August 04,20108:14 AM To: Hake, Cynthia S. (CMSjCMM) Subject: RE: FYI - Provenge

Yes, C9273. We don't see a need to code just yet so maybe January for the physiCian office.

John Warrenl Director, Division of Ambulatory Services I Hospital and Ambulatory Policy Group I Center for Medicare Management ICenters for Medicare & Medicaid Servicesl7500 Security Blvd, Baltimore, MD 212441 Mail Stop C4-01-26I voice: (410) 766-36331 fax: (410) 766-4490 I e-mail: [email protected]

From: Hake, Cynthia S. (CMSjCMM) Sent: Tuesday, August 03, 2010 5:29 PM To: Warren, John F. (CMSjCMM) Subject: RE: FYI - Provenge

2


Do you happen to know if there is a "c" code out there for Provenge now? OR are we looking at January for a J code?

Would ask Marjorie about the C code, but she's vacating.

From: Warren, John F. (CMS/CMM) Sent: Tuesday, August 03, 2010 3:40 PM To: Hake, Cynthia S. (CMS/CMM) Subject: RE: FYI - Provenge

Paying for it as a drug. OCSQ is doing an NCD.

John Warrenl Director, Division of Ambulatory Services I Hospital and Ambulatory Policy Group I Center for Medicare Management I Centers for Medicare & Medicaid Services I 7500 Security Blvd, Baltimore, MD 212441 Mail Stop C4-01-261 voice: (410) 786-36331 fax: (410) 786-4490 I e-mail: [email protected]

From: Hake, Cynthia S. (CMS/CMM) Sent: Tuesday, August 03, 2010 2:41 PM To: Warren, John F. (CMS/CMM) Subject: FW: FYI - Provenge

Hi John-

I've missed a couple of workgroup meetings while on a detail, but heard that you formulated a position on this, Can you tell me in a nutshell?

Please and thanks!

Cindy

From: Bonnell, Claudia [mailto:[email protected]] Sent: Tuesday, August 03, 20108:55 AM To: Hake, Cynthia S. (CMS/CMM); Baldo, Marjorie D. (CMS/CMM); Gilbreath, Cheryl (CMS/CMM) Subject: FYI - Provenge

You probably already know about this - but in case you don't.. ..

Dendreon's $93,000 Cancer Drug Price Must Be Paid by U.S., Doctors Say

3


By Tom Randall - Aug 2, 2010

Dendreon Inc.'s $93,000 price tag for its Provenge prostate cancer treatment must be covered under the rules of the U.S. Medicare health plan, according to a letter submitted by the American Society of Clinical Oncology.

The Centers for Medicare & Medicaid Services, the government agency that determines which treatments will be reimbursed, is required by the Social Security Act to pay for all cancer drugs approved by U.S. regulators, the cancer society said in a public letter submitted to the agency.

Provenge won marketing rights in the U,S. in April, becoming the first drug designed to train the body's immune system to fight cancer. Medicare, the government's health plan for the elderly and disabled, routinely pays for medicines once they've been approved regardless of price. The agency initiated a yearlong internal review on June 30 to determine whether Provenge should be an exception.

"We are concerned that CMS may have plans to examine the issue of whether to cover this therapy for its FDA-approved indications," the Alexandria, Virginia-based cancer society said in a letter posted on a CMS website for public comments. ''This would be both counter-productive and ill-advised."

Dendreon rose 93 cents, or 2.9 percent, to $33.84 at 4 p.m. New York time in Nasdaq Stock Market composite trading. The stock has declined 33 percent since the drug was approved on April 29.

28,000 Doctors

The American Society of Clinical Oncology represents 28,000 cancer doctors and medical practitioners. The group. holds the world's biggest annual meeting devoted to cancer drug research.

Treatment with Provenge costs about $93,000 for three doses administered over the course of a month. The medicine helped patients live about 4.1 months longer than those given a placebo, according to tests used to gain approval.

Before the review was announced, Don McLeod, an agency spokesman, said Provenge would almost certainly be covered by Medicare. He declined to comment today on the review.

4


The agency doesn't typically make formal determinations on cancer drugs. Instead, it pays claims through the local contractors who administer payments.

"Under any scenario, we urge CMS to provide clear public statements regarding Medicare's current policies governing the coverage of this therapy," ASCO said in the comments to Medicare. "Ambiguity and uncertainty regarding coverage policies can act as an unacceptable barrier to medically necessary care." .

To contact the reporter on this story: Tom Randall in New York at [email protected].

5



From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, September 03,20109:21 AM To: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ) Subject: Provenge MEDCAC Questions v4 090310.doc Attachments: Provenge MEDCAC Questions v4 090310.doc

Here is the new version of the questions with changes from Lori and to address Saty's concern with using 2 adjectives (i.e., clinically significantly). Please provide comments so Jim may send to Louie. Thank you!

1



From: Fitterman,. Leslye (CMS/OCSQ) Sent: Friday, September 03,201010:06 AM To: Larson, Tricia Cc: Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ): Pencek, Eileen (CMS/OCSQ) Subject: Dendreon letter on August 20, 2010

Dear Ms. Larson:

On behalf ofthe CMS Coverage and Analysis team performing the national coverage analysis on autologous immunotherapy treatment of metastatic prostate cancer, we appreciate your letter to us dated August 20, 2010. A response to the letter from Mr. Bishop will be included in the draft decision memorandum on this product. The draft decision memorandum must be completed and available for public comment by March 30,2011.

Best regards, Leslye

Leslye Fitterman, PhD. Centers for Medicare and Medicaid Services Office of Clinical Standards and Quality Coverage and Analysis Group 7500 Security Boulevard C1-09-06 Fax - 410-786-9286 Phone - 410-786-1806 Email - [email protected]

1



From: Pencek, Eileen (CMS/OCSQ) Sent: Friday, September 03, 2010 1 :50 PM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questions v4 090310.doc Attachments: Provenge MEDCAC Questions v4 090310 revisions(2).doc

Leslye, Attached are my revisions. I changed the' questions to reflect Saty's suggestion without, reworking the questions too much. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, September 03, 2010 9:21 AM . To: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ) Subject: Provenge MEDCAC Questions v4 090310.doc

Here is the new version of the questions with changes from Lori and to address Saty's concern with using 2 adjectives (i.e., clinically significantly). Please provide comments so Jim may send to louie. Thank you!

1


(b)(6)(b)(6)


(b)(6)


(b)(6)


mail is prohibited. If you have received this e-mail in error, please notify the sender by replying to this message and delete this e-mail immediately.

'.

2


(b)(6)(b)(6)

(b)(6)


Lou~

************* IMPORTANT - PLEASE READ ********************

This e-mail, including attachments, may include confidential and/or proprietary information, and may be used only by the person or entity to which it is addressed. If the reader of this e-mail is not the intended recipient or his or her authorized agent, the reader is hereby notified that any dissemination, distribution or copying of this email is prohibited. If you have received this e-mail in error, please notify the sender by replying to this message and delete this e-mail immediately.

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 8:37 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James

(CMS/OCSQ) Subject: Provenge MEDCAC Questions FI 090810.doc Attachments: Provenge MEDCAC Questions FI 090810.doc

Here are questions for the MEDCAC that were approved by Cliff and Saty. Please review one last time for let me know if the document is ready to be posted.

Thanks, Leslye

1

\.



From: Pencek, Eileen (CMS/OCSQ) Sent: Monday, September 13, 2010 9:23 AM To: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James

(CMS/OCSQ) Subject: RE: Provenge MEDCAC Questions FI 090810.doc

Leslye, Looks good. One minor revision: In the FDA Label description at the top of the page prior to the questions, the words castrate resistant should be hyphenated in order to keep it consistent with the 'rest of the document. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 8:37 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: Provenge MEDCAC Questions FI 090810.doc


Thanks, Leslye

...,

1

I



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 9:28 AM To: Rollins, James (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questions FI 090810.doc

Thank you!

From: Rollins, James (CMSjOCSQ) Sent: Monday, September 13, 2010 9:27 AM To: Fitterman, Leslye (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ) Subject: RE: Provenge MEDCAC Questions FI 09081O.doc

Looks fine. Jarollins

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 2010 8:37 AM To: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: Provenge MEDCAC Questions FI 090810.doc


Thanks, Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 12:00 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: MEDCAC Presentations

Alright!

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, September 13, 2010 11:58 AM To: Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ) Subject: RE: MEDCAC Presentations

They are not an invited speaker. They can do what other manufacturers have done in the past and use the usual process.

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 2010 11:49 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: MEDCAC Presentations

Therefore, do I say "no" to Dendreon?

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, September 13, 2010 11:45 AM To: Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) . Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Ei~een (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: MEDCAC Presentations

GAPPnet was not the product in the same sense as Provenge. The underlying topic for the May 2009 MEDCAC was desirable characteristics of evidence on genetic screening tests. So it looks like we do not have an actual case of a manufacturer speaking at a meeting where coverage of its own product was the topic.

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 2010 11:07 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: FW: MEDCAC Presentations

Louis and Tamara:

This is a follow-up to our discussion several weeks ago regarding Dendreon's request for a 20 - 30 minute presentation to the MEDCAC on Nov lth. You wanted to know if at any prior MEDCACs the sponsor was allowed to present. I believe that the case identified by Michel_e, Steve Teutcsh presentation on GAPPnet and his role as an voting member ofthe committee at the May 6, 2009 meeting, may represent a precedent for allowing Dendreon to present. In addition, Dendreon will not be sitting on the committee at all.

1


Please let me know your thoughts on next steps with Dendreon.

Leslye

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 10:59 AM To: Atkinson, Michelle L. (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: MEDCAC Presentations

He was also a member of Genomic Applications in Practice and Prevention Network (GAPPNeFM ): A ,

National Collaboration for Realizing the Promise of Genomics in Health Care and Disease Prevention.

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Monday, September 13, 2010 10:23 AM To: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: MEDCAC Presentations

It was on the May 6,2009 Screening for Genetic Testing, Steven Teutsch, MD, MPH, was a voting panel member and a guest speaker.

Michelle

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 10:06 AM To: Atkinson, Michelle L. (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: MEDCAC Presentations

Thank you!

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Monday, September 13, 2010 10:03 AM To: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: MEDCAC Presentations

I have been looking this up and I have not found the exact meeting yet. I will continue to look and as soon as I find it I will let you know.

Thanks Michelle

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 7:28 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: FW: MEDCAC Presentations

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, September 02, 20102:56 PM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: MEDCAC Presentations

Maria & Michele:

The PROVENGE Team has spoken with Louis and Tamara regarding the request from Dendreon to have a 20 minute time slot to present their product at the MEDCAC scheduled for November 17, 2010. CAG management would like to know if this has been permitted at a prior MEDCAC and if so,can you provide examples.

Thanks in advance!

Leslye

i I I

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 12:01 PM To: Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ) . . Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ellis, MariaA

(CMS/OCSQ) Subject: RE: MEDCAC Presentations

Jim:

I agree. They will sign up to present.

From: Rollins, James (CMSjOCSQ) Sent: Monday, September 13, 2010 12:00 PM To: Jacques, Louis B. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ) Subject: RE: MEDCAC Presentations

So that means that Dendreon will not be given the opportunity to give a presentation. But I am sure that there will be representatives in the audience to give a 5 minute public comment. Jarollins

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, September 13, 2010 11:58 AM To: Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ) . Subject: RE: MEDCAC Presentations

They are not an invited speaker. They can do what other manufacturers have done in the past and use the usual process.

__ __• ___ .•w ••. _._.......__ .......___....~.~_.._._.....__••.•__~ ___.~ .~ ~_· ._~ .~.

, . From: Fitterman, Leslye (CMSjOCSQ)

Sent: Monday, September 13, 2010 11:49 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: MEDCAC Presentations

Therefore, do I say "noJl to Dendreon?

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 13, 2010 11:45 AM To: Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMSjOCSQ);.Rollins, James (CMSjOCSQ) Subject: RE: MEDCAC Presentations

GAPPnet was not the product in the same sense as Provenge. The underlying topic for the May 2009 MEDCAC was desirable characteristics of evidence on genetic screening tests. So it looks like we do not have an actual case of a manufacturer speaking at a meeting where coverage of its own product was the topic.

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 2010 11:07 AM

1


To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins,James (CMSjOCSQ) Subject: FW: MEDCAC Presentations

Louis and Tamara:

This is a follow-up to our discussion several weeks ago regarding Dendreon's request for a 20"';' 30 minute presentation to the MEDCAC on Nov 17th • You wanted to know if at any prior MEDCACs the sponsor was allowed to present. I believe that the case identified by Michele, Steve Teutcsh presentation on GAPPnet and his role as an voting member of the

. committee at the May 6, 2009 meeting, may represent a precedent for allowing Dendreon to present. In addition,

Dendreon will not be sitting on the committee at all.

Please let me know your thoughts on next steps with Dendreon.

Leslye

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 10:59 AM To: Atkinson, Michelle L. (CMS/OCSQ);'ElliS, Maria A. (CMSjOCSQ) Subject: RE: MEDCAC Presentations

He was also a member of Genomic Applications in Practice and Prevention Network (GAPPNet'M): A

National Collaboration for Realizing the Promise of Genomics in Health Care and Disease Prevention.

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Monday, September 13, 2010 10:23 AM To: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ)' Subject: RE: MEDCAC Presentations

It was on the May 6,2009 Screening for GeneticTesting, Steven Teutsch, MD, MPH, was a voting panel member and a guest speaker.

Michelle

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 2010 10:06 AM To: Atkinson, Michelle L. (CMS/OCSQ)i Ellis, Maria A. (CMSjOCSQ) Subject: RE: MEDCAC Presentations

Thank you!

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Monday, September 13, 2010 10:03 AM To: Fitterman, Leslye (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ) Subject: RE: MEDCAC Presentations .

2


I have been looking this up and I have not fo~nd the exact meeting yet. I will continue to look and as soon as I find it I will let you know.

Thanks Michelle

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, September 13, 20107:28 AM To: Ellis, Maria A. (CMSjOCSQ); Atkinson, Michelle L. (CMSjOCSQ) Subject: FW: MEDCAC Presentations

From: Fitterman, Leslye (CMSjOCSQ) Sent: Thursday, September 02, 2010 2:56 PM To: Ellis, Maria A. (CMSjOCSQ); Atkinson, Michelle L. (CMSjOCSQ) Subject: MEDCAC Presentations

Maria & Michele:

The PROVENGE Team has spoken with louis and Tamara regarding the request from Dendreon to have a 20 minute time slot to present their product at the MEDCAC scheduled for November 17, 2010. CAG management would like to know if this has been permitted at a prior MEDCAC and if so can you provide examples.

Thanks in advance!

leslye

3



From: Pencek, Eileen (CMS/OCSQ) Sent: Monday, September 13,201012:02 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Mitchell Sokoloff, MD, FACS

Leslye, Dr Sokoloff looks very well qualified to be a guest panelist for the MEDCAC. I think we should invite him and set up a call to discuss the expectations of a guest panelist. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 11:14 AM To: Pencek, Eileen (CMS/OCSQ) Subject: FW: Mitchell Sokoloff, MD, FACS

From: Saphire-Bernstein, Inger [mailto:[email protected]] sent: Friday, September 03, 2010 5:26 PM To: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMSjOCSQ) Cc: Kosiak, Beth; Stinchcomb, Stephanie. Subject: Mitchell Sokoloff, MD, FACS

The AUA is pleased to highly recommend Dr. Mitchell Sokoloff as the presenter on the assessment and treatment of advanced prostate cancer that you requested for the MedCAC meeting on November 17. Dr. Sokoloff is Professor of Surgery and Chief of Urology; Division of Urology, Department of Surgery, University of Arizona College of Medicine. His CV is attached. Dr. Sokoloff is a national clinical leader in prostate cancer treatment and an excellent presenter. Please let me know if you would like me to organize a conference call with Dr. Sokoloff and CMS staff.

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 201012:04 PM To: Pencek, Eileen (CMS/OCSQ)

. Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Mitchell Sokoloff, MD, FACS

Agree and we will discuss with Lori tomorrow.

From: Pencek, Eileen (CMS/OCSQ) Sent: Monday, September 13, 2010 12:02 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Mitchell Sokoloff, MD, FACS

Leslye, Dr Sokoloff looks very well qualified to be a guest panelist for the MEDCAC. I think we should invite him and set up a call to discuss the expectations of a guest panelist. Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 2010 11:14 AM To: Pencek, Eileen (CMS/OCSQ) Subject: FW: Mitchell Sokoloff, MD, FACS

From: Saphire-Bernstein, Inger [mailto:[email protected]] Sent: Friday, September 03, 2010 5:26 PM To: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Cc: Kosiak, Beth; Stinchcomb, Stephanie Subject: Mitchell Sokoloff, MD, FACS

The AUA is pleased to highly recommend Dr. Mitchell Sokoloff as the presenter on the assessment and treatment of advanced prostate cancer that you requested for the MedCAC meeting on November 17. Dr. Sokoloff is Professor of Surgery and Chief of Urology; Division of Urology, Department of Surgery, University of Arizona College of Medicine. His CV is attached. Dr. Sokoloff is a national clinical leader in prostate cancer treatment and an excellent presenter. Please let me know if you would like me to organize a conference call with Dr. Sokoloff and CMS staff.

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 20102:56 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: Inquiry from Senators Specter and Keryy Attachments: cms-senators-spector-kerry.gif; SUM-ADMIN Specter Kerry Ikf 091310.doc; Specter Kerry

provenge Ikf 091310 Ibj.doc

Louis:

Attached please find the letter sent to Dr. Berwick, a draft response and a draft summary statement to address the inquiry received from Senators Specter and Kerry. Jim has reviewed these and I have incorporated his changes.

Thanks,

Leslye

1


(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional


(b)(5) - Predecisional(b)(5) - Predecisional


(b)(5) - Predecisional












From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 13, 20104:00 PM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

PASERCHIA, LORI A. (CMS/OCSQ) Subject: SUM-ADMIN Specter Kerry Ikf 091310 Ibj.doc Attachments: SUM-ADMIN Specter Kerry Ikf 091310 Ibj.doc

These are usually as little as possible so I shortened.

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 20104:07 PM To: Jacques, Louis B. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

PASERCHIA,LORI A. (CMS/OCSQ) Subject: RE: SUM-ADMIN Specter Kerry Ikf 091310 Ibj.doc

Thanks-

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, September 13, 2010 4:00 PM To: Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ) Subject: SUM-ADMIN Specter Kerry Ikf 091310Ibj.doc


1


· Rollins, James (CMS/OCSQ)

Fro.,,: Fitterman, Leslye (CMS/OCSO) Sent: Monday, September 13,20104:07 PM To: Jacques, Louis B. (CMS/OCSO); Rollins, James (CMS/OCSO); Pencek, Eileen (CMS/OCSO);

PASERCHIA, LORI A. (CMS/OCSO) Subject: RE: SUM-ADMIN Specter Kerry Ikf 091310 Ibj.doc

Thanks-

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 13, 2010 4:00 PM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: SUM-ADMIN Specter Kerry Ikf 091310 Ibj.doc


1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 13, 20104: 11 PM To: Ashby, Lori M. (CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Spector Kerry letter re PROVENGE Attachments: Specter Kerry provenge 091310 Ibj rev.doc; SUM-ADMIN Specter Kerry 091310 Ibj.doc

Lori:

Attached please find the response letter and summary statement as finalized by Louis.

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, September 14, 20107:41 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: 11/17 MEDCAC Questions for Posting Attachments: Provenge MEDCAC Questions FI 090810.doc

Maria:

Here are the questions for the November lih MEDCAC as reviewed and approved by Cliff and Saty as well as the CAG

team, including Louis.

leslye

1



From: Fitterman, Lestye (CMS/OCSQ) Sent: Tuesday, September 14, 20108:40 AM To: [email protected] Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ)

Subject: Request from Dendreonto present at the 11/17 MEDCAC

Dear Chris:

Interested parties (including manufacturers) may request presentation time by submitting an email along with their PowerPoint presentation to [email protected] by the deadline which will be stated in the Federal Register Notice to be posted at the end of the month. The allotted time for any individual presenter will be determined by the number of requests. Manufacturers do not have special status in the MEDCAC presentation process.

If Dendreon wishes to submit written comments before the meeting we will make them available to ~he MEDCAC panelists. The MEDCAC questions will be posted by the end of September on the same day the Federal Register Notice is published. Both documents may be found on the CMS CAG website on the date the Federal Register notice is

published.


Leslye Fitterman, PhD. Centers for Medicare and Medicaid Services Office of Clinical Standards and Quality Coverage and Analysis Group

7500 Security Boulevard C1-09-06 Fax - 410-786-9286 Phone - 410-786-1806 Email- [email protected]

1



From: Madan, Ravi (NIH/NCI) [E) Sent: Tuesday, September 14, 2010 1:.30 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Gulley, James (NIH/NCI) [E) Subject: RE: An invitation to a Medicare advisory committee meeting

Dear Lori,

Thank you for your invitation. I am happy to accept. Please let me know what I need to do to register etc.

I look forward to taking part in this meeting.

Sincerely,

Ravi A Madan, MD Assistant Clinical Investigator Laboratory of Tumor Immunology and Biology & Medical Oncology Branch National Cancer Institute

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, September 14, 2010 10:00 AM To: Madan, Ravi (NIH/NCI) [E] Cc: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Gulley, James (NIH/NCI) [E] Subject: An invitation to a Medicare advisory committee meeting

Dr. Madan,

Thank you for your CV and for offering to assist us.

We want to invite you to sit as a guest expert panelist for this MEDCAC meeting. The goal of the meeting is to advise CMS on the current status of the evidence regarding the impact of autologous cellular immunotherapy on health outcomes in patients with metastatic prostate cancer to include the identification of any gaps in the evidence base and recommendations regarding how best to fill these gaps. The MEDCAC panel will include up to fifteen panelists with relevant expertise. .

I am happy to answer any questions that you might have about this invitation. Thank you for your consideration.

Sincerely,

Lori


From: Madan, Ravi (NIH/NCI) [E] Sent: Friday, September 10, 2010 11:25 PM

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To: Gulley, James (NIH/NCI) [E]; PASERCHIA, LORI A. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Dear Lori,

Attached is my CV as you requested.

Ilook forward to attending the meeting and assisting any way Iam able.

Have a nice weekend.

Sincerely,

Ravi A. Madan, MD Associate Clinical Investigator Laboratory of Tunmor Immunology and Biology & Medical Onology Branch National Cancer Institute

From: Gulley, James (NIH/NCI) [E] Sent: Tuesday, September 07, 2010 12:47 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Madan, Ravi (NIH/NeI) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Lori,

It was nice to talk to you and the team this afternoon about the upcoming MEDCAC meeting. Attached is my CV. By way of this email, Iam also asking Dr. Madan to send his CV.

Best,

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-17S0 Bethesda, MD 20892

(3e1) 435-2956 Voice (301) 48~-5e94 Fax (3e1) 496-1211 Page Operator

webpage: <http://ccr.cancer.gov/Staff/Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles!gulley/default.asp MOB Website: http://medicaloncology.cancer.gov/

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 12:22 PM

2


To: Gulley, James (NIH/NCI) [E] Cc: Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

OK. It's on our calendar. Thanks.

Looking forward to talking with you.

Have a great holiday weekend,

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 41

From: Gulley, James (NIH/NCI) [E] Sent: Friday, September 03, 2010 1f:08 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Great-let's say 12:30-1pm then.

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology &Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda,MD 20892

(301) 435-2956 Voice (301) 480-5094 Fax (301) 496-1211 Page Operator

webpage~ <http://ccr.cancer.gov!Staff!Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles/gulley!default.asp MOB Website: http://medicaloncology.cancer.gov/

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 10:56 AM To: Gulley, James (NIH/NCI) [E] Cc: Madan, Ravi (NIH/Ncr) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Tues it is. Right now our calendars are open from 9-10 am and from 12-3 pm. Let me know what 30-minute time slot works for you. r

Lori

Lori A. Paserchia, MD Coverage and AnalysiS Group

3


Centers for Medicare and Medicaid Services Lori. Paserch [email protected]

1

From: Gulley, James (NIH/NCI) [E] Sent: Friday, September 03, 2010 10:28 AM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Dahut, William (NIH/NO) [E]i Madan, Ravi (NIH/NCI) [E]i Fitterman, Leslye (CMS/OCSQ)i Rollins, James (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Great-yes, I will be available either today (after 3:30) or Tuesday. I will be in clinic on Tuesday but could step out for 3045 min at a time that is convenient for you.

Best,

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director~ Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N20S, MSC-1750 Bethesda, MD 20892


webpage: <http://ccr.cancer.gov/Staff/Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles!gulley!default.asp MOB Website: http://medicaloncology.cancer.gov/

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 10:25 AM To: Gulley, James (NIH/NCI) [E] Cc: Dahut, William (NIH/NCI) [E]i Madan, Ravi (NIH/NO) [E]i Fitterman, Leslye (CMS/OCSQ)i Rollins, James (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee m~eting

Dr. Gulley,

Wonderful. Thank you for agreeing to participate inour MEDCAC. I think it would be most productive to continue our conversation (ie, work out the details) via phone. Are you available to talk today or preferably next Tuesday?

Also, the MEDCAC is an open, public meeting. Dr. Madan is very welcome to attend.

Regards,

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Cent~rs for Medicare and Medicaid Services Lori. [email protected] 410.786.2115

4


From: Gulley, James (NIH/NCI) [E] Sent: Thursday, September 02, 2010 2:56 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Dahut, William (NIH/NO) [E]; Madan, Ravi(NIH/NCI) [E] Subject: RE: An invitation to a Medicare advisory committee meeting

Dr. Paserchia,

I can be available that day to give a general overview of metastatic castration resistant prostate cancer. Let me know if you need anything from me.

I also leftyou a phone message to ask if this was a closed meeting or if I could also have a colleague, Dr. Ravi Madan who is another prostate cancer clinical researcher at the NCI attend. Thanksfor the opportunity.

Sincerely,

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892

(301) 435-2956 Voice (301) 480-S094 Fax (301) 496-1211 Page Operator

webpage: <http://ccr.cancer.gov/St~ff/Staff.asp?StaffIO=S17>

Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles/gulley/default.asp MOB Website: http://medicaloncology.cancer.gov/

From: Dahut, William (NIH/NCI) [E] Sent: Thursday, September 02, 2010 8: 11 AM To: Madan, Ravi (NIH/NCI) [E]; Gulley, James (NIH/NCI) [E] Subject: FW: An invitation to a Medicare advisory committee meeting

. . . I am at the retreat for the NIH leadership course that day. Are either one of you available on November 17 ?

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Thursday, September 02, 20107:41 AM To: Oahut, William (NIH/NCI) [E] Subject: RE: An invitation to a Medicare advisory committee meeting

Or.Oahut,

Thank you for your prompt reply. I'm sorry to hear that you cannot join us on that day.

Do you have a recommendation for someone else we can invite to give this presentation? We prefer someone who is a Federal employee but will consider someone who is not.

Lori

5


Lori A Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected]

15 "';"';";;;'~.~.:...;;.;.;;;";"';";;"'",~-".""--"."",-"-~--""""",,,,,...~..--.............- ..- ...............--.............. --.-- ..- ........... - ..~.....- ...........-,----....~~..---..__.__.. From: Dahut, William (NIH/NCI) [E] Sent: Wednesday, September 01, 2010 11:22 AM To: PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Dr Paserchia,

This a very important discussion. Unfortunately I have a conflict that day that I cannot move.

bill

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 10:00 AM To: Dahut, William (NIH/NCI) [E] Cc: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: An invitation to a Medicare advisory committee meeting

Dear Dr. Dahut,

My name is Lori Paserchia. I'm a Medical Officer with the Coverage and Analysis Group (CAG) at The Centers for Medicare and Medicaid Services (CMS). The role of CAG is to develop evidence-based national coverage policies, referred to as national coverage determinations (NCDs), in order to provide timely access to reasonable and necessary services and technologies to improve health outcomes for Medicare beneficiaries.

The CMS will be convening a meeting of its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) on November 17, 2010 to look at the recently FDA approved PROVENGE, an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. We have called this meeting to consider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer. This meeting is in conjunction with an NCD that is currently in progress.

The CMS invites you to give a 30-45 minute overview of "metastatic prostate cancer 101" during this MEDCAC meeting so that all committee members who are not urologists will at least have a common understanding of the diagnosis and treatment options for men with this stage of prostate cancer. The MEDCAC will be held at the CMS Central Office in Baltimore from 8 am til 4:30 pm.


Sincerely,

Lori A Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 410.786.2115

6



From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, September 14, 2010 1 :37 PM To: Madan, Ravi (NIH/NCI) [E] Cc: Fitterman, Leslye (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Rollins, James (CMS/OCSQ);

Pencek, Eileen (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Hi Ravi,

Thank you for accepting. We greatly appreCiate it. If you have questions about or want to generally discuss your participation on our MEDCAC panel, please let me know and we can set up a time to chat via phone.

Our MEDCAC coordinator, Maria Ellis, will help you with the administrative details regarding your MEDCAC participation. I have cc'ed her on this email.

We look forward to meeting and working with you.

Regards,

Lori

Lori A. PaSerchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 410.786.2115.- ..~-,.~-.-.- ...- ..--.... -- ~-""'''''~''''

From: Madan, Ravi (NIH/NCI) [E] Sent: Tuesday, September 14, 2010 1:30 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Fitterrnan, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Gulley, James'(NIH/NCI) [E] Subject: RE: An invitation to a Medicare advisory committee meeting

Dear Lori,

Thank you for your invitation. I am happy to accept. Please let me know what I need to do to register etc.

I look forward to taking part in this meeting.

Sincerely,

'- Ravi A Madan, MD Assistant Clinical Investigator Laboratory of Tumor Immunology and Biology & Medical Oncology Branch National Cancer Institute

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, September 14, 2010 10:00 AM

1


To: Madan, Ravi (NIH/NCI) [E] Cc: Fitterman, Leslye (CMS/bcsQ); Rollins, James (CMS/OCSQ); Gulley, James (NIH/NtI) [E] Subject: An invitation to a Medicare advisory committee meeting

Dr. Madan,

Thank you for your CV and for offering to assist us. .

We want to invite you to sit as a guest expert panelist for this MEDCAC meeting. The goal of the meeting is to advise CMS on the current status of the evidence regarding the impact of autologous cellular immunotherapy on health outcomes in patients with metastatic prostate cancer to include the identification of any gaps in the evidence base and recommendations regarding how best to fill these gaps. The MEDCAC panel will include up to fifteen panelists with relevant expertise.


Sincerely,

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 410.786.2115

From: Madan, Ravi (NIH/NCI) [E] sent: Friday, September 10, 2010 11:25 PM To: Gulley, James (NIH/NCI) [E]; PASERCHIA, LORI A. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Dear Lori,

Attached is my CV as you requested.

I look forward to attending the meeting and assisting any way I am able.

Have a nice weekend.

Sincerely,

Ravi A. Madan, MD Associate Clinical Investigator Laboratory of Tunmor Immunology and Biology & Medical Onology Branch National Cancer Institute

. From: Gulley, James (NIH/NCI) [E] Sent: Tuesday, September 07, 2010 12:47 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye(CMS/OCSQ) . Subject: RE: Ar invitation to a Medicare advisory committee meeting

2


Lori.

It was nice to talk to you and the team this afternoon about the upcoming MEDCAC meeting. Attached is my CV. By way ofthis email, I am also asking Dr. Madan to send his CV.

Best,

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology &Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892


webpage: <http://ccr.cancer.gov/Staff/Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles/gulley/default.asp MOB Website: http://medicaloncology.cancer.gov/

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 12:22 PM To: Gulley, James (NIH/NCI) [E] Cc: Madan, Ravi (NIH/NO) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

OK. It's on our calendar. Thanks.

Looking forward to talking with you.

Have a great holiday weekend,

Lori


From: Gulley, James (NIH/NCI) [E] Sent: Friday, September 03, 2010 12:08 PM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Great-let's say 12:30-1pm then.

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology

3


& Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892


webpage: <http://ccr.cancer.gov/Staff/Staff.asp?StaffID-517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles/gulley/default.asp MOB Website:. http://medicaloncology.cancer.gov/

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 10:56 AM To: Gulley, James (NIH/NCI) [E] Cc: Madan, Ravi (NIH/NCI) [E]; Fittertnan, Leslye (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Tues it is. Right now our calendars are open from 9-10 am and from 12-3 pm. Let me know what 3D-minute time slot works for you.

Lori

Lori A Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 410.786.2115 .._----._--_ ........•....•.

From: Gulley, James (NIH/NCI) [E] Sent: Friday, September 03, 2010 10:28 AM To: PASERCHIA, LORI A. (CMS/OCSQ) Cc: Dahut, William (NIH/NCI) [E]; Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Great-yes, I. will be available either today (after 3:30) or Tuesday. I will be in clinic on Tuesday but could step out for 3045 min at a time that is convenient for you.

Best,

James

James L. Gulley, M.D., Ph.D.,F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Principal Investigator, Medical Oncology Branch , Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892



4


From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Friday, September 03, 2010 10:25 AM To: Gulley, James (NIH/NCI) [E] Cc: Dahut, William (NIH/NCI) [E]; Madan, Ravi (NIH/NCI) [E]; Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) . Subject: RE: An invitation to a Medicare advisory committee meeting

Dr. Gulley,

Wonderful. Thank you for agreeing to participate in our MEDCAC. I think it would be most productive to continue our conversation (ie, work out the details) via phone. Are you available to talk today or preferably next Tuesday?

Also, the MEDCAC is an open, public meeting. Dr. Madan is very welcome to attend.

Regards,

Lori


From: Gulley, James (NIH/NCI) [E] Sent: Thursday, September 02,2010 2:56 PM To: PASERCHIA, LORI A.(CMS/OCSQ) Cc: Dahut, William (NIH/NCI) [E]; Madan, Ravi (NIH/NCI) [E] Subject: RE: An invitation to a Medicare advisory committee meeting

Dr. Paserchia,

I can be available that day to give a general overview of metastatic castration resistant prostate cancer. Let me know if you need anything from me.

I also left you a phone message to ask if this was a closed meeting or if I could also have a colleague, Dr. Ravi Madan who is another prostate cancer clinical researcher at the NCI attend. Thanks for the opportunity.

Sincerely,

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology &Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda,MD 20892


webpage: <http://ccr.cancer.gov!Staff!Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles!gulley!default.asp

5


MOB Website: http://medicaloncology.cancer.gov/

From: Dahut, William (NIH/NCI) [E] Sent: Thursday, September 02,20108:11 AM To: Madan, Ravi (NIH/NCI) [E]; Gulley, James (NIH/NCI) [E] Subject: FW: An invitation to a Medicare advisory committee meeting

I am at the retreat for the NIH leadership course that day. Are either one of you available on November 17 7

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Thursday, September 02, 2010 7:41 AM To: Dahut, William (NIH/NCI) [E] Subject: RE: An invitation to a MediCare advisory committee meeting

Dr. Dahut,

Thank you for your prompt reply. I'm sorry to hear that you cannot join us on that day.

Do you have a recommendation for someone else we can invite to give this presentation? We prefer someone who is a Federal employee but will consider someone who is not.

Lori

Lori A. Paserchia, MO Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. [email protected] 410.786.2115 --~~~~-,---~"".,~,~---,.,,~--,

From: Dahut, William (NIH/NCI) [E] Sent: Wednesday, September 01, 2010 11:22 AM To: PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: An invitation to a Medicare advisory committee meeting

Dr Paserchia,

This a very important discussion. Unfortunately I have a conflict that day that I cannot move.

bill

From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Wednesday, September 01, 2010 10:00 AM To: Dahut, William (NIH/NCr) [E] Cc: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: An invitation to a Medicare advisory committee meeting

Dear Dr. Oahut,

My name is Lori Paserchia. I'm a Medical Officer with the Coverage and Analysis Group (CAG) at The Centers for Medicare and Medicaid Services (CMS). The role of CAG is to develop evidence-based national coverage policies, referred to as national coverage determinations (NCDs), in order to provide timely access to reasonable and necessary services and technologies to improve health outcomes for Medicare beneficiaries.

The CMS wi" be convening a meeting of its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) on November 17, 2010 to look at the recently FDAapproved PROVENGE~ an autologous ce"ular

6


immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. We have called this meeting to consider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer. Thi~ meeting is in conjunction with an NCO that is currently in progress.

The CMS invites you to give a 30-45 minute overview of "metastatic prostate cancer 101" during this MEDCAC meeting so that all committee members who are not urologists will at least have a common understanding of the diagnosis and treatment options for men with this stage of prostate cancer. The MEDCAC will be held at the CMS Central Office in Baltimore from 8 am til 4:30 pm.


Sincerely,

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori. Paserch [email protected] 410.786.2115

7



From: Ellis, Maria A. (CMS/OCSQ) Sent: Thursday, September 16, 2010 9:44 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORIA (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: November MEDCAC - new invitees Attachments: MEDCAC Roster 11.17.10.doc

Good Morning!

Attached is the updated drqfi MliDCAC rosterji}r the November 171h meeting .and 'we have qUOrlUrl. I)lease tet rneknow tfl can be C!ffurther assistance.

J. Sanford Schwartz - He is checking his schedule. Diane Meier - She is not a MEDCAC panel member Robert Steinbrook - He accepted the invite.

Heall}1 Insurance Spedah:'it j)ivi'iioIl oFOperatioIls aIld IIlwl111alioIl M;magcIIlcIlt Coverage aIld AIlalysi'i Group, OG.5Q (410) 786-030.9

[email protected]

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, September 14, 2010 10:00 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ) . Subject: November MEDCAC - new invitees.

Maria:

Please let Dr. Dale Fuller know that we would like for him to attend. In addition, please extend invitations to the following:

J. Sanford Schwartz Diane Meier Robert Steinbrook

FYI- We have an acceptance from (Presenter) James L. Gulley, M.D ., Ph.D., F.A.C.P.

1


Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology, & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute, national Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892 301-435-2956 (voice) 301-496-1211 (page operator)

Thanks, Leslye

2



From: Ellis, Maria A. (CMS/OCSQ) Sent: Thursday, September 16, 2010 9:47 AM To: Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ) Subject: FW: Information post-call from today.

Good Morning!

See email below regarding Saty'spartiClpation at the Novelnber 17'h

MEDCAC rneeting.

Heald} hlSUr;lllCe Specialist J)iVl:5ion ofOperations ;llld IIl/(}FInatioIl Management Covera,ge andAnalysL5 (;lVlIp, OCSQ (410) 786-0309

[email protected]

From: Smith, Renee K. (eMS/OOM) Sent: Thursday, September 16, 2010 9:17 AM To: Ellis, Maria A. (CMS/OCSQ) Subject: RE: Information post-call from today.

Maria,

There is no conflict that would require an additional waiver for Satya-Murti.

Review of his OGE 450 submitted states that he participated in a onetime consultation in February with Dendreon

through Foley Haag.

That is permissible as he participated because of his expertise.

Therefore no further action is required.

1


Renee Smith

Ethics Program Analyst

410-786-0471

From: Ellis, Maria A. (CMS/OCSQ) Sent: Wednesday, September 15, 2010 2:47 PM To: Smith, Renee K. (CMS/OOM) Subject: FW: Information post-call from today.

}{eaitlL Il1surance Specia1i'it DiVJ:'iioil oIOperatioils and InformaLionManagewent Coverage andAnaiysis GrolJP, O($Q (410) 786-030.9

[email protected]

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Wednesday, September 15, 2010 2:46 PM To: Ellis, Maria A. (CMS/OCSQ) Subject: FW: Information post-call from today.

Here you go!

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Tuesday, August 24, 2010 9:37 AM To: Ellis, Maria A. (CMS/OCSQ) Subject: FW: Information post-call from today.

2


Making sure you have all info!

From: Smith, Renee K. (CMS/OOM) Sent: Tuesday, June 29, 2010 8:57 AM To: Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: Information post-call from today.

Michelle,

Dr. Saty Satya-Murti shouldhavecompJeted a HHS 520 ( Request for Approval of OutSide Activity) for the consultative services he provided for Provenge. I will need additional information to make a decision. (Example: focus for the November meeting & his consultative involvement) .

Contact me if you have any additional questions ..

Renee

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Tuesday, June 29, 2010 8:23 AM To: Smith, Renee K. (CMS/OOM) Subject: FW: Information post-call from today.

Renee,

Could you please read below and let me know what you think? If he would or would not be able to participate in an upcoming MEDCAC meeting on Provenge. If you have any questions, please let me know~

Thankyou

Michelle

From: Syrek Jensen, Tamara S. (CMS/OCSQ) Sent: Wednesday, June 16,20105:13 PM To: Graves, Patricia A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: FW: Information post-call from today.

When you get a chance, let's discuss. Saty may have aconnict of interest for the November MEDCAC. My guess is that we need to run his name by ethics sooner rather than later. thanks

3


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From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, September 16, 20109:54 AM To: Ellis, Maria A. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); PASERCHIA. LORI A. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: November MEDCAC - new invitees Attachments: R Madan CV.doc; Sokoloff AUA CV 0823 2010.doc

Thankyou!

As noted below, Dr. Gulley will be an invited presenter. Dr. Madan and Dr. Sokoloff will be guest panelists. Their CVs are attached.

Leslye

From: Ellis, Maria A. (CMSjOCSQ) Sent: Thursday, September 16, 2010 9:44 AM To: Fitterman, Leslye (CMSjOCSQ) Cc: Pencek, Eileen (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Rollins, James (CMSjOCSQ); Atkinson, Michelle L. (CMSjOCSQ) Subject: RE: November MEDCAC - new invitees

Good Morning!

Attached is the uj)dateddrqft ME~DCAC rosterfbr the November 17th rneeting and zve have quorum. Please let rne knozv if'I can be C!ffitrther assistance.

J. Sanford Schwartz - He is checking his schedule. Diane Meier - She is not a MEDCAC panel member Robert Steinbrook - He accepted the invite.

Ifcaldl Insur.wce Specialist Division ofOperations and IllforrnalionManagcment Covcrage andAnaly;<;i5 Group, OCS'Q (410) 786-0309

[email protected]

From: Fitterman, Leslye (CMSjOCSQ) Sent: Tuesday, September 14,2010 10:00 AM

1


To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ) Subject: November MEDCAC - new invitees

Maria:

Please let Dr. Dale Fuller know that we would like for him to attend. In addition, please extend invitations to the following:

J. Sanford Schwartz Diane Meier Robert Stein brook

FYI- We have an acceptance from (Presenter) James L. Gulley, M.D ., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology, & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute, national Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892 301-435-2956 (voice) 301-496-1211 (page operator)

Thanks, Leslye

2



From: Ellis, Maria A. (CMS/OCSQ) Sent: Monday, September 20,20109:04 AM To: Fitterman, Leslye (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ) Subject: November 17th MEDCAC Attachments: MEDCAC Roster 11.17.10.doc

Clood Morning!

Attached is the draft roster for the Novernber 17thME~DCAC rneeting on ]Jrovenge. l~lease revie'w and ?!you agree I 'will contact thern letting them, know that they have been selected and to save the date.

Healdl1nsurance Speciab:'it DiVJ:"iOTl oIOperatioTls and InfonnaiionManage1l1el1t Coverage andAnalys/~' Group, OC5Q (410) 786-030.9

[email protected]

1



From: Stieber, Joan (CMS/OL) Sent: Monday, September 20,20104:16 PM To: Jacques, Louis B. (CMS/OCSQ); Rollins, James (CMS/OCSQ); SCHAFER, JYME H.

(CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) Subject: FW: question re: Provenge NCA

Please forgive us (I know how busy you are right now) but here's another Congressional conference call request -from Energy & Commerce minority staff (on behalf of Health Subcommittee Ranking Member Rep. Shimkus, R-IL) who would like to talk with us about the NCA on Dendreon/Provenge.

They are seeking more information on why CMS decided an NCA was necessary for on-label use of an FDA-approved cancer treatment. They've been asked to write and circulate a letter on this issue but say they'd prefer to leave the inquiry "as informal as possibleJl

•

The Committee staff suggested Thursday afternoon or sometime Friday for this call (with a possible preference for Friday). Who would be the best staff to participate from our end, and would they be available on either of those day? If so, what times would be best?

thanks very much - Joan in OL

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On Tue, Sep 7, 2010 at 6:32 AM, Jacques, Louis B. (CMS/OCSQ) <[email protected]> wrote:

Cliff and Saty

Attached redline changes per recent emails. Also reworded to get grammatical agreement between question stems and responses.

Louis

************* IMPORTANT - PLEASE READ ********************

This e-mail, including attachments, may include confidential and/or proprietary information, and may be used only by the person or entity to which it is addressed. If the reader of this e-mail is not the intended recipient or his or her authorized agent, the reader is hereby notified that any dissemination, distribution or copying of this email is prohibited. If you have received this e-mail in error, please notify the sender by replying to this message and delete this e-mail immediately.

2


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From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23,20105:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); . PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ)

Subject: Provenge MEDCAC Questionsfor posting Ibj.doc Attachments: Provenge MEDCAC Questionsfor posting Ibj.doc

OK to post. Please take a close look final proofread. I did change the phrasing from

1. in patients who are asymptomatic or minimally symptomatic who have metastatic, castrate resistant prostate cancer?

to

2. inpatients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer? .

to match the labeled indication wording more closely.

Sipuleucel-T (Provenge)is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-t is designed to work by an immunological effect.

1



From: Graves, Patricia A. (CMS/OCSQ) Sent: Friday, September 24,20101:21 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Manlove, John (CMS/OCSQ)

Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

Once this has been proofread (per Louis' note below), please reply and John will post. Thanks!.

From: Jacques, Louis B. (CMSjOCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc



. to

2. in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer?


Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease .. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect theimpact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

1



From: Dolina, Elaine L. (CMS/OCSQ) Sent: Monday, September 27,20108:25 AM To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ)

Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc Attachments: Provenge MEDCAC Questions FI 090810.htm

Attached is the HTML version ready to go. Are we clear for takeoff?

Elaine

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/qCSQ); caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc

OKto post. Please take a close look final proofread. I did change the phrasing from


to


to match the la,beled indication wording more closely.

Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the s~udy results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27,20108:31 AM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James


Subject: Re: Provenge MEDCAC Questionsfor posting Ibj.doc

Ok to post Sent from my Blackberry

From: Dolina, Elaine L. (CMS/OCSQ) To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 27 08:25:07 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc


Elaine

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc



to



Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

1


2


.

1.

2.


From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 27,20108:31 AM To: Jacques, Louis B. (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); . PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ)


I agree!

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, September 27, 2010 8:31 AM To: Dolina, Elaine L. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ) Subject: Re: Provenge MEDCAC Questionsfor posting Ibj.doc

. Ok to post Sent from my Blackberry

~"~_._________• • >M'" __ n_~u__

From: Dolina, Elaine L. (CMSjOCSQ) To: Jacques, Louis B. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ) Sent: Mon Sep 27 08:25:07 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc


Elaine

From: Jacques, Louis B. (CMSjOCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Rollins, James (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc


in patients who are asymptomatic or minimally symptomatic who have metastatic, castrate resistant prostate cancer?

to

in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer?


1



2



From: Dolina, Elaine L. (CMS/OCSQ) Sent: Monday, September 27, 20108:38 AM To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OGSQ); Rollins, James

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A (CMS/OCSQ)


I just snagged the FR notice, so I'" wait for that to load and then add them to the MEDCAC page together.

Elaine

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 27, 2010 8:31 AM To: Jacques, Louis B. (CMS/OCSQ); Dolina, Elaine L.(CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

I agree!

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27, 2010 8:31 AM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Re: Provenge MEDCAC Questionsfor postinglbj.doc


From: Dolina, Elaine L. (CMS/OCSQ) To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 27 08:25:07 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc


Elaine

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ);. caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) . Subject: Provenge MEDCAC Questionsfor posting Ibj.doc


1



to



Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant {hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

2


From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc



to




2



From: Dolina, Elaine L. (CMS/OCSQ) Sent: Monday, September 27,201011:.12 AM To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James



Posted!

http://www.cms.gov!mcd!viewmcac.asp?from2=viewmcac.asp&where=index&mid=56

I also added the FR notice and the link to register online.

From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)i Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ)i Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ)i Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc

.OK to post. Please take a close look final proofread. I did change the phrasing from


to



Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, . pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27,20108:45 AM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James


Subject: Re: Provenge MEDCAC Questionsfor posting Ibj.doc

Ok Sent from my Blackberry

From: Dolina, Elaine L. (CMS/OCSQ) To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 27 08:38:06 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

I just snagged the FR notice, so I'll wait for that to load and then add them to the MEDCAC page together.

Elaine

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 27,20108:31 AM To: Jacques, Louis B. (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

I agree!

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27, 2010 8:31 AM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Re: Provenge MEDCAC Questionsfor posting Ibj.doc


From: Dolina, Elaine L. (CMS/OCSQ) To: Jacques, Louis B. (CMSjOCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMSjOCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ)i Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 27 08:25:07 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc


Elaine 1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27, 2010 11 :22 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: Fw: Provenge MEDCAC Questionsfor posting Ibj.doc

If bcbs wants to see questns they're public now Sent from my Blackberry

From: Dolina, Elaine L. (CMS/OCSQ) To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 2711:12:052010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj,doc

Posted!

http://www.cms,gov/mcd/viewmcac.asp?from2=viewmcac.asp&where=index&mid=56


From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc



to



Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reyiewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

1


2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, September 27,201012:20 PM To: Rollins, James (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

I sent an email to Elise.

From: Rollins, James (CMS/OCSQ) Sent: Monday, September 27, 2010 12:10 PM To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

Leslye, we can contact Elise ancj let her know that the questions are posted. She can let BXBS know so that they can review them and do what they need to do. Jarollins

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, September 27, 2010 11:22 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Subject: Fw: Provenge MEDCAC Questionsfor posting Ibj.doc

If bcbs wants to see questns they're public now Sent from my Blackberry

From: Dolina, Elaine L. (CMS/OCSQ) To: Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); caplan, Stuart (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)i Graves, Patricia A. (CMS/OCSQ) Sent: Mon Sep 27 11:12:05 2010 Subject: RE: Provenge MEDCAC Questionsfor posting Ibj.doc

Posted!

http://www.cms.gov/mcd/viewmcac.asp?from2=viewmcac.asp&where=index&mid=56


From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, September 23, 2010 5:04 PM To: Dolina, Elaine L. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ)iSyrekJensen, Tamara S. (CMS/OCSQ); Caplan, Stuart (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)i Graves, Patricia A. (CMS/OCSQ) Subject: Provenge MEDCAC Questionsfor posting Ibj.doc


1. in patients who are asymptomatic or minimally sy~ptomatic who have metastatic, castrate resistant prostate cancer?

to

1




Sipuleucel-T (Provenge) is being licensed for the following indication: PROVENGE is indicated for the treatment of asymptomatic or minimally symptomatic metastatic' castrate resistant (hormone refractory) prostate cancer. This indication reflects the population studied. The product is novel and it is not known if the study results are generalizable to a broader population with more advanced disease. As noted in the clinical reviewers' memo, pain is a prognostic factor for survival for castrate resistant (hormone refractory) patients and the amount of residual disease could affect the impact of this therapy since Sipuleucel-T is designed to work by an immunological effect.

'\

2



From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday, September 29, 20109:21 AM To: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); SCHAFER, JYME H.

(CMS/OCSQ) . Subject: FW:MEDCAC

From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday, September 29, 2010 9:03 AM To: Graves, Patricia A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: MEDCAC . .

http://blog.mrnicegeek.com/201 0/03/02/dendreon-anatomy-of-a-wall-streek-fck/

Link to a blog about the person contacting the MEDCAC members.

Louis B. Jacques, MD Director, Coverage & Analysis Group Office of Clinical·Standards and Quality Centers for Medicare & Medicaid Services Mailstop C1-09-06 7500 Security Blvd Baltimore MD 21244 (410) 786-4512 (410) 786-9286 (FAX) [email protected]

1


ROllins. James (CMS/OCSQ)

From: SCHAFER, JYME H. (CMS/OCSQ) Sent: Thursday, September 30, 2010 3:00 PM To: Rollins, James (CMS/OCSQ) Subject: FW: Spector rewrite Attachments: Rewrite 9 24 10 Proveng Specter Kerry drafts.docx

From: Brown-Jones, Shanterri M. (CMS/OCSQ) Sent: Thursday, September 30, 2010 2:51 PM To: SCHAFER, JYME H. (CMS/OCSQ) Cc: Ashby, Lori M. (CMS/OCSQ) Subject: Spector rewrite

Please see attached rewrite with comments from OL. Barry cleared it already as is but I wanted you to have a chance to take look before it goes back to OSORA. I left the comments included.

Thanks

OfJhanl/Jrri (5:Br~f7II(ff Correspondence Liaison Specialist Office of Clinical Standards and Quality . Centers for Medicare & Medicaid Services Email: [email protected] Tel:410-786-6854 Fax:41 0-786-6857

.1



From: Jacques, Louis B. (CMS/OCSO) Sent: Thursday, September 30,20104:24 PM To: Rollins,James (CMS/OCSO); Fitterman, Leslye (CMS/OCSO) Subject: RE: Spector rewrite

Looks fine

From: Rollins, James (CMS/OCSQ) Sent: Thursday, September 30, 2010 3:41 PM To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMSjOCSQ) Subject: FW: Spector rewrite

Here is a rewrite of a document by OL that Louis had originally created in response to a letter from Arlen Spector. Jarollins

From: SCHAFER, JYME H. (CMS/OCSQ) Sent: Thursday, September 30, 2010 3:00 PM To: Rollins, James (CMS/OCSQ) Subject: FW: Spector rewrite

From: Brown-Jones, Shanterri M. (CMS/OCSQ) Sent: Thursday, September 30, 2010 2:51 PM To: SCHAFER, JYME H. (CMS/OCSQ) Cc: Ashby, Lori M. (CMS/OCSQ) Subject: Spector rewrite


Thanks

0fJ1wttorri c:5Br~t7IIIJS' Correspondence Liaison Specialist Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Email: [email protected] Tel: 41 0-786-6854 Fax:41 0-786-6857

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, October 01, 2010 10:37 AM To: Rollins, James (CMS/OCSQ) Subject: RE: Spector rewrite

Thanks -I saved it

From: Rollins, James (CMS/OCSQ) Sent: Thursday, September 30,20103:41 PM To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ) Subject: FW: Spector rewrite

Here is a rewrite of a document by OL that Louis had originally created in response to a letter from Arlen Spector. Jarollins

From: SCHAFER, JYME H. (CMS/OCSQ) Sent: Thursday, September 30, 2010 3:00 PM To: Rollins, James (CMS/OCSQ) Subject: FW: Spector rewrite

From: Brown-Jones, Shanterri M. (CMS/OCSQ) Sent: Thursday, September 30, 20102:51 PM To: SCHAFER, JYME H. (CMS/OCSQ) Cc: Ashby, Lori M. (CMS/OCSQ) Subject: Spector rewrite

Please see attached' rewrite with comments from OL. Barry cleared it already as is but 1 wanted you to have a chance to take look before it goes back to OSORA. I left the comments included.

Thanks

otJJran!lJ!1i c5ie3rtm'llddfl(ff Correspondence Liaison Specialist Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Email: [email protected] Tel: 410-786-6854 Fax:410-786-6857

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, October 01, 2010 2:04 PM To: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Eggleston, Lisa J. (CMS/OCSQ) Subject: FW: Provenge slides Attachments: Provenge PEP 09302010 (b).pptx; Sipuleucel-T _NEJM1001294.pdf

Team:

I learned today about the attached presentation from CMM for a Pharmacists Education Program session on PROVENGE that was given yesterday. Let's review the slides and then we may meet with Cheryl if we have any questions. Thanks to

Lisa for introducing me to Cheryl.

Leslye

From: Gilbreath, Cheryl (CMS/CMM) Sent: Friday, October 01, 2010 1:52 PM To: Fitterman, Leslye (CMS/OCSQ); Eggleston, Lisa J. (CMS/OCSQ) Cc: Dombrowski, Robert (CMS/CPC); Warren, John F. (CMS/CMM) Subject: RE: Provenge slides

Great to meet you Leslye,

Thank you for including me in the loop regarding the NCAfor Provenge. I've CCd John Warren, my Division Director who may also be interested in listening in the upcoming open forum meeting regarding the NCA.

Attached is the slide-deck and copy of the article that was presented at yesterday's CMS Pharmacists Education Program.

I've CC'd Bob Dombrowsky, the Coordinator for the Pharmacists Education Program as he may be interested to know where these slides are going beyond the PEP...

I hope it doesn't clog your inbox too much ©

Cheryl Gilbreath, PharmD, MBA, R.Ph. Health Insurance Specialist, Division Cif Ambulatory Services 1Hosp.ital and Ambulatory Policy Group I Center for Medicare Management I Centers for Medicare & Medicaid Services 17500 Security Blvd, Baltimore, MD 212441 Mail Stop C4"01-26I voice: (410) 786-59191fax: (410) 786-4490 I e-mail: [email protected]

CONFIDENTIALITY NOTICE: This e-mail message, including any attachments, is for the sole use of the intended recipient(s) and may contain confidential and privileged information or otherwise protected by law. Any unauthorized review, use, disclosure or distribution is prohibited. If you are not the intended recipient, please contact the sender by reply e-mail and destroy al/ copies of the original message.

From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, October 01, 2010 12:16 PM To: Eggleston, Lisa J. (CMS/OCSQ); Gilbreath, Cheryl (CMS/CMM) Subject: RE: Provenge slides

Cheryl:

Here is the link to the tracking sheet that contains a link to the meeting announcement and the questions the MEDCAC will address. I look forward to sharing the slides with the team working on this NCA.

1


http://www.cms.gov/mcd/viewtrackingsheet.asp?id=247

Leslye

2



From: Ashby, Lori M. (CMS/OCSQ) Sent: Monday, October 04,2010 7:46 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: SCHAFER, JYME H. (CMS/OCSQ) Subject: FW: Spector rewrite Attachrnents: Rewrite 9 2410 Proveng Specter Kerry drafts.docx

Please See below-it was sent to DMSS by mistake. Let me know asap this morning what your reactions are to the comments. If there's something major that we should run by louis first let me know that as well. Thanks!

Lori M. Ashby

Special Assistant OCSQ/Coverage and Analysis Group 410-7866322 [email protected]

Notice: The contents of this message and any attachments 111ay be privileged and confidential. Please do not disseminate without the approval of the Centers for Medicare &:: Medicaid Services. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy, forward, disseminate, or othervvise use the information. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intend.ed to waive any applicable privilege.

From: Brown-Jones, Shanterfi M. (CMSjOCSQ) Sent: Thursday, September 30, 2010 2:51 PM To: SCHAFER, JYME H. (CMSjOCSQ) Cc: Ashby, Lori M. (CMSjOCSQ) Subject: Spector rewrite


Thanks

OfJlttmttJrric5e3rt71t7llr:::!(J1/{If Correspondence Liaison Specialist Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Email: [email protected] Tel:41 0-786-6854 Fax:410-786-6857

1



From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October OS, 2010 9:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ);Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ)

Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: *Response needed: Scheduling Update Call for Provenge TA

Importance: High

Good morning,

Please send me your availability for a 1-hour call on Tuesday (today), Wednesday, and Thursday.

Thank you very much,

Kim


1



From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05,20109:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ)

Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: *Response needed: Scheduling Update Call for Provenge T A

Importance: High

Good morning,



Kim


1



From: Pencek, Eileen (CMS/OCSQ) Sent: Tuesday, October 05,201012:09 PM To: Wittenberg, Kim (AHRQ/COE) Cc: Schott, Lawrence H. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: FW: Scheduling Evidence Forum for Provenge

Kim,

Yes. We have scheduled the "Effectiveness of Sipuleucel-T (Provenge)" Evidence Forum for Tuesday, October 26th . Elise. Berliner confirmed this date with David Mark from BCBSA.

We look forward to the forum here at CMS in the media center on 10/26. Any questions or concerns feel free to call me.

Thanks for your help.

Eileen Pencek 410-768-2273

From: Schott, Lawrence H. (CMS/OCSQ) Sent: Tuesday, October 05,2010 11:15 AM To: Pencek, Eileen (CMS/OCSQ) Subject: FW: Scheduling Evidence Forum for Provenge

Since I'm no longer personally scheduling any new forums, please respond to Kim and let me know of any potential change regarding the pre-MEDCAC presentation of the BCBS TA for Provenge.

To the best of my knowledge, this is still on for 10/26. Correct?

Thanks very much, Eileen.

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October OS, 2010 9:40 AM To: Schott, Lawrence H. (CMS/OCSQ) Subject: FW: Scheduling Evidence Forum for Provenge

Good morning,

I just wanted to confirm the Provenge Evidence Forum date. I have 10/26 in my notes. Is this date confirmed?

Thank you in advance for this information,

1


Kim


From: Berliner, Elise (AHRQ) Sent: Wednesday, September 01, 2010 9:30 AM To: 'Mark, David'; Wittenberg, Kim (AHRQ/COE); 'Aronson, Naomi'; 'Flaherty, Sharon' Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: RE: Scheduling Evidence Forum for Provenge

The MedCAC date has been announced: http://www.cms.gov/mcd/viewmcac.asp?from2=viewmcac.asp&where=index&mid=56&

Dendreon: Medicare Coverage Fears Allayed SEATTLE (The Street) -- The U.S. agency in charge of Medicare has scheduled a meeting for Nov. 17 to discuss the use of Dendreon's(DNDN) prostate cancer vaccine Provenge.

The meeting announcement was posted Tuesday on the web site of the Centers for Medicare and Medicaid Services (eMS).

"The Centers for Medicare and Medicaid Services (eMS) has called this meeting toconsider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer," the agency's announcement stated.

The fact that CMS is focusing its attention on which prostate cancer patients to treat with Provenge and will not consider the broader question ofwhether or not to reimburse at all for the $93,OOO-per-treatment drug is a positive and should help allay investor concerns.

Deutsche Bank biotech analyst Robyn Karnauskas in a note to clients Tuesday night said she expects CMS will conclude that Provenge coverage should hue closely to the type of prostate cancer patients that were treated in the Provenge clinical trials.

That outcome "will not change street estimates in our view," Karnauskas writes, adding, "These eligibility criteria we expect to be put in place are in-line with those ofthe IMPACT trial. This is the way that we, and the Street, model Provenge's market opportunity." Karnauskas has a buy rating on Dendreon with a $44 price target.

Dendreon shares rollercoastered in June when eMS announced that it was opening an assessment to determine a national coverage decision ofProvenge, which received FDA approval earlier this year as a treatment for advanced prostate cancer.

2


Since that announcement, Dendreon has indicated that 14 of the 15 regional Medicare caniers are either already reimbursing patients for Provenge or have signaled their intention to do so. Strong demand for Provenge in the form of patients on waiting lists to receive the drug has also been reported by the company.

Dendreon shares closed Tuesday up 15 cents to $35.84 but jumped another 66 cents, or almost 2% to $36.50 once investors became aware of the scheduling of the Medicare meeting.

--Written byAdam Feuerstein in Boston.

From: Mark, David [mailto:[email protected]] Sent: Thursday, August 26, 20104:57 PM To: Wittenberg, Kim (AHRQ/COE); Aronson, Naomi; Flaherty, Sharon Cc: Samson, David; Sarsany, Lisa; Berliner, Elise (AHRQ) Subject: RE: Scheduling Evidence Forum for Provenge

Tuesday Oct 26 would work for me. David Mark.

From: Wittenberg, Kim (AHRQlCOE) [mailto:[email protected]] Sent: Wednesday, August 25,20103:10 PM To: Aronson, Naomi; Flaherty, Sharon Cc: Mark, David; Samson, David; Sarsany, Lisa; Berliner, Elise (AHRQ) Subject: Scheduling Evidence Forum for Provenge Importance: High

Good afternoon,

eMS contacted me today with a potential date for the Provenge Evidence Forum. Would you be available on Tuesday, October 26? The meeting will convene at 2 pm and run until 3 pm. It's best to arrive by 1 :30 pm. The presenters will be finished and available to leave for the airport (BWI is closest) by 4 pm. Please let me know if 10/26 would work for you.

Thank you, Kim


From: Berliner, Elise (AHRQ) Sent: Friday, August 13, 20104:29 PM To: 'Aronson, Naomi'; 'Flaherty, Sharon' Cc: 'Mark, David'; 'Samson, David'; 'Sarsany, Lisa'; Wittenberg, Kim (AHRQlCOE) Subject: RE: FDA Approves Provenge

We also received the following email today from an attorney.

3


I think that speculating on the immunological effects are beyond the scope of the TA, but I think it would be good to document any objective data on the question of how many lymphocytes are removed by the Dendreon procedure and how many are left in the patient's body (I have seen conflicting numbers in the press) and any studies of the effect of the removal of the lymphocytes on survival or other outcomes in healthy controls vs. cancer patients of different ages. The TA should explicitly state whether the evidence is sufficient to determine whether or not the placebo procedure itself caused a harm and the evidence of the effect of other issues related to the design of the trial (especially the timing of the procedure itself, the crossovers, the use of chemp etc.) on the observered outcome.

I am sure you have already thought about these issues, but I just wanted to let you know about the email we received .

. Thanks, Elise

From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Friday, August 13,20103:52 PM To: Wittenberg, Kim (AHRQjCOE) Subject: follow-up re immune aging expertise for Provenge TA

Kim:

I hope you (and Elise) feel better soon and you manage to get everything in order for your trip. Here are the pOints I was referring to in our conversation regarding the need for immune aging expertise in the Provenge T A. If you or Elise have any questions or want to discuss, please do call or write.

• eMS is engaged in a coverage analysis to decide the extent to which it will cover Provenge as a treatment for advanced prostate cancer.

• Administering Provenge involves processing a patient's blood to initially remove 90% of a patient's circulating, cancer--fighting immune cells, which are then further purified and treated to make Provenge. This 'manufacturing' process has the side effect of causing the loss of >50% of these immune cells.

• When the trials for Provenge were conducted, the control group also underwent the removal and processing of these immune cells. But instead of reinjecting all the remaining cells into the subjects, two-thirds of them were frozen and preserved for possible later treatment with Provenge.

• Therefore, at each of three sessions, the experimental group lost -50% of these cells in their system at the time and placebo patients lost -86%.


4



• Experts who understand how massively the immune system changes around age 70 have categorically told us that elderly patients are harmed if these cells are removed, because their boqies are not able to replace the removed cells with equally vigorous or the same types of replacement cells. The consequence is a shortened survival, particularly in patients with active cancer. This nuance regarding older patients is one that has emerged in the field of immune aging after the Provenge trials were originally designed.

• While the Provenge trials took away a much greater percentage of immune cells from placebo patients than from Provenge patients, patients under 65 were not affected by either level of removal and lived longest (all patients <65 lived 28-29 months in the trials). Older patients with 50% of cells removed lived 5.5 months less than the 29 months seen in younger patients from that arm and older patients with 86% of cells removed lived 11 months les than the 28.2 months seen in younger patients from that arm.


• It is possible, if not likely, that older patients are better off not undergoing the Provenge treatment and thereby losing so many of these vital cells. There was no such control group in the Provenge trials.

• ONLY immune aging experts (experts that study thymic decline, T cell receptor diversity declines, naIve T cell population declines, etc.) have the expertise pivotal to identifying the impact of the trial design on the actual outcomes for Provenge in older patients. Immunologists who do not have this immune aging expertise focus on more general data and knowledge, which reflects the population as a whole and therefore is more reflective of the population under age 65. Such immunologists would be correct in believing that this cell loss is not meaningful to the average patient in the general population. In contrast, immune aging experts follow the knowledge developed

. by scientists in the last decade about the frailty of the aged immune system.


• The NIH's National Institute qf Aging has several immune aging experts who could provide their input to AHRQ. Others can be found at the University of Arizona, the Trudeau Institute, Stanford, Emory, UCLA, and Pittsburgh.

-- Demetrios


5


Covington & Burling LLP 1201 Pennsylvania Avenue, NW Washington, DC 20004-2401 http://www.cov.com/dkouzoukas/ [email protected] Tel: 202.662.5057 Assistant: Dee Perkins (202.662.6003, [email protected]) Fax: 202.778.5057 download vcard: http://www.cov.comlhiographies/vcard.aspx?Attorney=13540

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Aronson, Naomi [mailto:[email protected]] Sent: Friday, August 13, 2010 10:46 AM To: Berliner, Elise (AHRQ); Flaherty, Sharon Cc: Mark, David; Samson, David; Sarsany, Lisa; Wittenberg, Kim (AHRQ/COE) Subject: Re: FDA Approves Provenge

Confirming receipt. We will address these issues. Naomi Aronson, PhD Executive Director Technology Evaluation Center Blue Cross Blue Shield Association 312.297.5530 [email protected]

From: Berliner, Elise (AHRQ) <[email protected]> To: Flaherty, Sharon Cc: Aronson, Naomi; Mark, David; Samson, David; Sarsany, Lisa; Wittenberg, Kim (AHRQjCOE) <[email protected]> Sent: Fri Aug 13 09:29:18 2010 Subject: RE: FDA Approves Provenge

Just checking to see if you received the email below ...

I haven't gotten an acknowledgement from you, and we have been having some email issues ...

thanks, Elise

From: Berliner, Elise (AHRQ) Sent: Wednesday, August 04, 2010 10:00 AM To: 'Flaherty, Sharon' Cc: 'Aronson, Naomi'; 'Mark, David'; 'Samson, David'; 'Sarsany, Lisa'; Wittenberg, Kim (AHRQ/COE) Subject: RE: FDA Approves Provenge

Hi BCBSA TEC Provenge team,

6

v


Dendreon met with us yesterday to discuss the data. Here are some of my thoughts after the meeting:

1. The TA should definately include a future research section. The trials did not measure QOL, symptoms or pain over time. (The original study design for IMPACT included pain as an outcome, but it was taken out).

2. Many of the comments to CMS are about patients desire for an alternative with fewer side effects than chemo. But it would be good to clarify clearly that the studies show that Prevenge is NOTa substitute for chemo, most patients got chemo anyway.

3. Timing of chemo/progression of symptoms: Also a future research item. In the IMPACT study Provenge arm got chemo ,...1.6 months EARLIER than the control group. (what does this imply? The disease is still progressing on Provenge (consistent with no difference in progression-free survival??). Does the cancer progress any slower(or faster) with Provenge? Is any mortality benefit LIVING 4 months longer or DYING for 4 months longer? If I were making a decision for my family members, I would want to know how long the patient would be pain free/symptom free with or without Provenge).

4. Patient inclusion criteria: The NEJM article on the IMPACT study defined the patient population as asymptomatic or minimally symptomatic with no further explanation. Dendreon said that the protocol was on the NEJM website, but the specific criteria was: no opiod analgesics within 21 days and average weekly pain score of 3 or less on visual analog scale. It is important for the TA to be clear on the inclusion criteria for the trials.

Thanks so much. Let me know if you need any further information from Dendreon, it would be best if we were the intermediaries in communication.

Thanks, Elise

7



From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05,201012:17 PM To: Pencek, Eileen (CMS/OCSQ)

·Cc: Schott, Lawrence H. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ)

Subject: RE: Scheduling Evidence Forum for Provenge

Thank you for the confirmation!

Sincerely, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville,MD 20850 Ph: 301~427-1488

Fax: 301-427-1639 E-mail: [email protected]

From: Pencek, Eileen (CMSjOCSQ) Sent: Tuesday, October OS, 2010 12:09 PM To: Wittenberg, Kim (AHRQjCOE) Cc: Schott, Lawrence H. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: FW: Scheduling Evidence Forum for Provenge

Kim,

Yes. We have scheduled the "Effectiveness of Sipuleucel-T {Provenge}" Evidence Forum for Tuesday, October 26th • Elise Berliner confirmed this date with David Mark from BCBSA.

We look forward to the forum here at CMS in the media center on 10/26. Any questions or concerns feel freeto call me.

Thanks for your help.

Eileen Pencek 410-768-2273

From: Schott, Lawrence H. (CMS/OCSQ) Sent: Tuesday, October 05,2010 11:15 AM To: Pencek, Eileen (CMS/OCSQ) Subject: FW: Scheduling Evidence Forum for Provenge

1


Since I'm no longer personally scheduling any new forums, please respond to Kim and let me know of any potential change regarding the pre-MEDCAC presentation of the BCBS TA for Provenge.

To the best of my knowledge, this is still on for 10/26. Correct?

Thanks very much, Eileen.

From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October OS, 2010 9:40 AM To: Schott, Lawrence H. (CMS/OCSQ) Subject: FW: Scheduling EVidence Forum for Provenge

Good morning,

I just wanted to confirm the Provenge Evidence Forum date. I have 10/26 in my notes. Is this date confirmed?

Thank you in advance for this information, Kim


From: Berliner, Elise (AHRQ) Sent: Wednesday, September 01, 2010 9:30 AM To: 'Mark, David'; Wittenberg, Kim (AHRQ/COE); 'Aronson, Naomi'; 'Flaherty, Sharon' Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: RE: Scheduling Evidence Forum for Provenge

The MedCAC date has been announced: http://www.cms.gov/mcd/viewmcac.asp?from2=viewmcac.asp&where=index&mid=56&

Dendreon: Medicare Coverage Fears Allayed SEATTLE (TheStreet) -- The U.S. agency in charge of Medicare has scheduled a meeting for Nov. 17 to discuss the use ofDendreon's(DND~D prostate cancer vaccine Provenge.

The meeting announcement was posted Tuesday on the web site of the Centers for Medicare and Medicaid Services (CMS).

2.


.,-5.

"The Centers for Medicare and Medicaid Services (CMS) has called this meeting to consider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer," the agency's announcement stated.

The fact that CMS is focusing its attention on which prostate cancer patients to treat with Provenge and will not consider the broader question of whether or not to reimburse at all for the $93,OOO-per-treatment drug is a positive and should help allay investor concems.

Deutsche Bank biotech analyst Robyn Karnauskas in a note to clients Tuesday night said she expects CMS will conclude that Provenge coverage should hue closely to the type of prostate cancer patients that were treated in the Provenge clinical trials.

That outcome "will not change street estimates in our view," Karnauskas writes,adding, "These eligibility criteria we expect to be put in place are in-line with those of the IMP ACT trial. This is the way that we, and the Street, model Provenge's market opportunity." Kamauskas has a buy rating on Dendreon with a $44 price target.

Dendreon shares rollercoastered in June when eMS announced that it was opening an assessment to determine a national coverage decision of Provenge, which received FDA approval earlier this year as a treatment for advanced prostate cancer.

Since that announcement, Dendreon has indicated that 14 of the 15 regional Medicare carriers are either already reimbursing patients for Provenge or have signaled their intention to do so. Strong demand for Provenge in the form of patients on waiting lists to receive the drug has also been reported by the company.

Dendreon shares closed Tuesday up 15 cents to $35.84 butjumped another 66 cents, or almost 2% to $36.50 once investors became aware of the scheduling of the Medicare meeting.

--Written by Adam Feuerstein in Boston.

From: Mark, David [mailto:[email protected]] Sent: Thursday, August 26, 2010 4:57 PM To: Wittenberg, Kim (AHRQlCOE); Aronson, Naomi; Flaherty, Sharon Cc: Samson, David; Sarsany, Lisa; Berliner; Elise (AHRQ) Subject: RE: Scheduling Evidence Forum for Provenge

Tuesday Oct 26 would work for me. David Mark.

From: Wittenberg, Kim (AHRQlCOE) [mailto:[email protected]] Sent: Wednesday, August 25,20103:10 PM To: Aronson, Naomi; Flaherty, Sharon Cc: Mark, David; Samson, David; Sarsany, Lisa; Berliner, Elise (AHRQ) Subject: Scheduling Evidence Forum for Provenge Importance: High

Good afternoon,

eMS contacted me today with a potential date for the Provenge Evidence Forum. Would you be available on Tuesday, October 26? The meeting will convene at 2 pm and run until 3 pm. It's best to arrive by 1 :30 pm. The presenters will be finished and available to leave for the airport (BWI is closest) by 4 pm. Please let me know if 10/26 would work for you.

3


Thank you, Kim


From: Berliner, Elise (AHRQ) Sent: Friday, August 13, 2010 4:29 PM To: 'Aronson, Naomi'; 'Flaherty, Sharon' Cc: 'Mark, David'; 'Samson, David'; 'Sarsany, Lisa'; Wittenberg, Kim (AHRQ/COE) Subject: RE: FDA Approves Provenge

We also received the following email today from an attorney.

I think that speculating on the immunological effects are beyond the scope of the TA, but I think it would be good to document any objective data on the question of how many lymphocytes are removed by the Dendreon procedure and how many are left in the patient's body (I have seen conflicting numbers in the press) and any studies of the effect of the removal of the lymphocytes on survival or other outcomes in healthy controls vs. cancer patients of different ages. The T A should explicitly state whether the evidence is sufficient to determine whether or not the placebo procedure itself . caused a harm and the evidence of the effect of other issues related to the design of the trial (especially the timing of the procedure itself, the crossovers, the use of chemo etc.) on the observered outcome.

I am sure you have already thought about these issues, but I just wanted to let you know about the email we received ..

Thanks, Elise

From: Kouzoukas, Demetrios [mailto:[email protected]] Sent: Friday, August 13, 2010 3:52 PM To: Wittenberg, Kim (AHRQlCOE) Subject: follow-up re immune aging expertise for Provenge TA

Kim:

I hope you (and Elise) feel better soon and you manage to get everything in order for your trip. Here are the points I was referring to in our conversation regarding the need for immune aging expertise in the Provenge TA. If you or Elise have any questions or want to discuss, please do call or write.

• CMS is engaged in a coverage analysis to decide the extent to which it will cover Provenge as a treatment for. advanced prostate cancer.

4


• Administering Provenge involves processing a patient's blood to initially remove 90% of a patient's circulating, cancer--fighting immune cells, which are then further purified and treated to make Provenge. This 'manufacturing' process has the side effect of causing the loss of >50% of these immune cells.

• When the trials for Provenge were conducted, the control group also underWent the removal and processing of. these immune cells. But instead of reinjecting all the remaining cells into the subjects, two-thirds of them were frozen and preserved for possible later treatment with Provenge. .

• Therefore, at each of three sessions, the experimental group lost -50% of these cells in their system at the time and placebo patients lost -86%.


• However, as opposed to'normal, healthy adults, the loss ofsuch a great quantity of these cells is significant in an elderly population and is even more significant in an elderly population with advanced prostate cancer.

• Experts who understand how massively the immune system changes around age 70 have categorically told us that elderly patients are harmed if these cells are removed, because their bodies are not able to replace the removed cells with equally vigorous or the same types of replacement cells. The consequence is a shortened' survival, particularly in patients with active cancer. This nuance regarding older patients is one that has emerged in the field of immune aging after the Provenge trials were originally designed.

• While the Provenge trials took away a much greater percentage of immune cells from placebo patients than from Provenge patients, patients under 65 were not affected by either level of removal and lived longest (all patients <65 lived 28-29 months in the trials). Older patients with 50% of cells removed lived 5.5 months less than the 29 months seen in younger patients from that arm and older patients with 86% of cells removed lived 11 months les than the 28.2 months seen in younger patients from that arm.


• It is pOSSible, if not likely, that older patients are better off not undergoing the Provenge treatment and thereby losing so many of these vital cells. There was no such control group in the Provenge trials.

5


• ONLY immune aging experts (experts that study thymic decline, T cell receptor diversity declines, naIve T cell population declines, etc.) have the expertise pivotal to identifying the impact of the trial design on the actual outcomes for Provenge in older patients. Immunologists who do not have this immune aging expertise focus on more general data and knowledge, which reflects the population as a whole and therefore is more reflective of the population under age 65. Such immunologists would be correct in believing that this cell loss is not meaningful to the average patient in the general population. In contrast, immune aging experts follow the knowledge developed by scientists in the last decade about the 'frailty of the aged immune system.


• The NIH's National Institute of Aging has several immune aging experts who could provide their input to AHRQ. Others can be found at the University of Arizona, the Trudeau Institute, Stanford, Emory, UCLA, and Pittsburgh.

-- Demetrios

Demetrios L. Kouzoukas Covington & Burling LLP 1201 Pennsylvania Avenue, NW Washington, DC 20004-2401 http://www.cov .com/dkouzoukas/ [email protected] Tel: 202.662.5057 Assistant: Dee Perkins (202.662.6003, [email protected]) Fax: 202.778.5057 doWIiload vcard: http://www.cov .comlbiographies/vcard.aspx? Attomey= 13540

This message is from a law firm and may contain information that is confidential or legally privileged. Ifyou are not the intended recipient, please immediately advise the sender by reply e-mail that this message has been inadvertently transmitted to you and delete this e-mail from your system. Thank you for your cooperation.

From: Aronson, Naomi [mailto:[email protected]] Sent: Friday, August 13, 2010 10:46 AM To: Berliner, Elise (AHRQ); Flaherty, Sharon Cc: Mark, David; Samson, David; Sarsany, Lisa; Wittenberg, Kim (AHRQ/COE) Subject: Re: FDA Approves Provenge

Confirming receipt. We will address these issues. Naomi Aronson, PhD Executive Director Technology Evaluation Center Blue Cross Blue Shield Association 312.297.5530 [email protected]

From: Berliner, Elise (AHRQ) <[email protected]> To: Flaherty, Sharon

6


Cc: Aronson, Naomi; Mark, David; Samson, David; Sarsany, Lisa; Wittenberg, Kim (AHRQ/COE) <[email protected]> Sent: Fri Aug 13 09:29:182010 Subject: RE: FDA Approves Provenge

Just checking to see if you received the email below ...

I haven't gotten an acknowledgement from you, and we have been having some email issues ...

thanks, Elise

From: Berliner, Elise (AHRQ) Sent: Wednesday, August 04, 2010 10:00 AM To: 'Flaherty, Sharon' Cc: 'Aronson, Naomi'; 'Mark, David'; 'Samson, David'; 'Sarsany, Lisa'; Wittenberg, Kim (AHRQ/COE) Subject: RE: FDA Approves Provenge

Hi SCSSA TEC Provenge team,

Dendreon met with us yesterday to discuss the data. Here are some of my thoughts after the meeting:

1. The TA should definately include a future research section. The trials did not measure QOL, symptoms or pain over time. (The original study design for IMPACT included pain as an outcome, but it was taken out).

2. Many of the comments to CMS are about patients desire for an alternative with fewer side effects than chemo. Sut it . would be good to clarify clearly that the studies show that Provenge is NOT a substitute for chemo, most patients got chemo anyway.

3. Timing of chemo/progressiori of symptoms: Also a future.research item. In the IMPACT study Provenge arm got chemo -1.6 months EARLIER than the control group. (what does this imply? The disease is still progressing on Provenge (consistent with no difference in progression-free survival??). Does the cancer progress any slower (or faster) with Provenge? Is any mortality benefit LIVING 4 months longer or DYING for 4 months longer? If I were making a decision for my family members, I would want to know how long the patient would be pain free/symptom free with or without Provenge}.

4. Patient inclusion criteria: The NEJM article on the IMPACT study defined the patient population as asymptomatic or minimally symptomatic with no further explanation. Dendreon said that the protocol was on the NEJM website, but the specific criteria was: no opiod analgesics within 21 days and average weekly pain score of 3 or less on visual analog scale. It is important for the T A to be clear on the inclusion criteria for the trials.

Thanks so much. Let me know if you need any further information from Dendreon, it would. be best if we were the intermediaries in communication.

Thanks, Elise

7



From: Wittenberg, Kim (AHRQ/GOE) Sent: Tuesday, October 05,20102:03 PM . To: Rollins, James (GMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, LoUIs B.

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Importance: High

Good afternoon,

I'm having difficultly finding a time for this call -- would Friday at 1 pm ET work for you? Thank you in advance for letting me know this afternoon to help schedule this call!

Thank you again, Kim


From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October OS, 2010 10:43 AM To: Wittenberg, Kim (AHRQlCOE); Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: 1 PM Deadline: DOODLE POLL Scheduling Update Call for Provenge TA

Good morning,

To facilitate scheduling this time-sensitive meeting, I've created a Doodle Poll. Please insert your availability into this poll by 1 PM today.

Doodle link: http://doodle.com/participation.html?pollld=fuy56x2n36a7em5z

Thank you very much, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427':'1488

1


Fax: 301-427-1639 E-mail: [email protected]

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October OS, 2010 9:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: *Response needed: Scheduling Update Call for Provenge TA Importance: High

Good morning,



Kim


2


Rollins. James (CNiS/OCSQ)

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October05, 2010 2:04 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B.

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Pr<;lVenge TA

Back to the drawing board ....


From: Rollins, James (CMS/OCSQ) Sent: Tuesday, October 05, 2010 2:02 PM To: Wittenberg, Kim (AHRQlCOE); Fitterman, Leslye (CMSjOCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Friday is not a good day since it is a flex day for some of us. Jarollins

From: Wittenberg; Kim (AHRQlCOE) Sent: Tuesday, October 05, 2010 2:03 PM . To: Rollins, James (CMS/OCSQ); Fitterinan, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: **Friday at 1 PM: Scheduling Update Call for Provenge TA Importance: High

Good afternoon,



Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639

1



From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October OS, 2010 10:43 AM To: Wittenberg, Kim (AHRQlCOE); Berliner, Elise (AHRQ)"; 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: 1 PM Deadline: DOODLE POLL Scheduling Update Call for Provenge TA

Good morning,

To facilitate scheduling this time-sensitive meeting, I've created a Doodle Poll. Please insert your availability into this poll by 1PM today.

Doodle link: http://doodle.com/participation.html?pollld::::fuy56x2n36a7em5z



From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October OS, 2010 9:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' . Subject: *Response needed: Scheduling Update Call for Provenge TA Importance: High

Good morning,



Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488

2


Fax: 301~427-1639 E-mail: [email protected]

3


I' I,


From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 05, 2010 2:08 PM To: Wittenberg, Kim (AHRQ/COE); Berliner, Elise (AHRQ); Rollins, James (CMS/OCSQ);

Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE:**Fridayat 1 PM: Scheduling Update Call for Provenge TA

I can call in for a lPM this Friday.

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05, 20102:09 PM to: Berliner, Elise (AHRQ); Rollins, James (CMS/OCSQ)i Fitterman, Leslye (CMS/OCSQ)i Jacques, Louis B. (CMS/OCSQ)i Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update call for Provenge TA

The only time available for the EPC .this week is 1 pm on Friday or 7 am on Wednesday.


From: Berliner, Elise (AHRQ) Sent:Tuesday, October 05,20102:08 PM To: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)i Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Dear eMS team,

I know everyone is really busy, but I hope we can find a time to talk this week.

We have to discuss the timing of the peer review and posting for this report. As I am sure that you know better than us, there is a lot of controversy and a high level of interest. '

Thanks, Elise

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05, 2010 2:04 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)i Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

1




From: Rollins, James (CMSjOCSQ) Sent: Tuesday, October OS, 2010 2:02 PM To: Wittenberg, Kim (AHRQjCOE); Fitterman, Leslye (CMSjOCSQ); Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ). Cc: Berliner, Elise (AHRQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Friday is not a good day since it is a flex day for some of us. Jarollins

From: Wittenberg, Kim (AHRQjCOE) Sent: Tuesday, October OS, 2010 2:03 PM To: Rollins, James (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Berliner, Elise (AHRQ) Subject: **Friday at 1 PM: Scheduling Update Call for Provenge TA Importance: High .

Good afternoon,




'~--..~-.-~--------~ From: Wittenberg, Kim (AHRQjCOE)

..

Sent: Tuesday, October OS, 2010 10:43 AM To: Wittenberg, Kim (AHRQjCOE); Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMSjOCSQ); Jacques, Louis B. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ)

2


Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: 1 PM Deadline: DOODLE POLL Scheduling Update Call forProvenge TA

Good morning,

To facilitate scheduling this time-sensitive meeting, I've created a Doodle Poll. Please insert your availability into this poll by 1PM today.

DoodIe link: http://doodle.com/participation.html?pollld=fuy56x2n36a 7 em5z

Thank you very mUCh, Kim


From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October 05, 2010 9:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: *Response needed: Scheduling Update call for Provenge TA Importance: High

Good morning,



Kim


3



From: Berliner, Elise (AHRQ) Sent: Tuesday, October 05, 20102:17 PM To: Rollins, James (CMS/OCSQ); Wittenberg, Kim (AHRQ/COE); Fitterman, Leslye

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Jim and Leslye,

THANK YOU SO MUCH for your flexibility. BCBS is going to send us a PROVISIONAL draft tomorrow,Jhey are not done with the internal review of the statistical analysis, but it will be good to have the provisional draft in hand during the discussion.

Thanks, Elise

From: Rollins, James (CMS/OCSQ) Sent: Tuesday, October 05, 2010 2:09 PM To: Wittenberg, Kim (AHRQlCOE); Berliner, Elise (AHRQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

I can try to call in on Friday at lpm. What is the call in number? Jarollins

From: Wittenberg, Kim (AHRQlCOE) Sent: Tuesday, October 05, 2010 2:09 PM To: Berliner, Elise (AHRQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update call for Provenge TA

The only time available for the EPC this week is 1 pm on Friday or 7 am on Wednesday.


From: Berliner, Elise (AHRQ) Sent: Tuesday, October 05, 2010 2:08 PM To: Wittenberg, Kim (AHRQlCOE); Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: RE: **Friday at 1 PM: Scheduling Update call for Provenge TA

Dear CMS team,

1


I know everyone is really busy, but I hope we can find a time to talk this week.

We have to discuss the timing of the peer review and posting for this report. As I am sure that you know better than us, there is a lot of controversy and a high level of interest.

Thanks, Elise

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05, 2010 2:04 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)i Jacques, Louis B. (CMS/OCSQ)i Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA


Kim Marie Wittenberg, MA Agency for HealthcareResearch and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639 E-mail: [email protected]

From: Rollins, James (CMS/OCSQ) Sent: Tuesday, October 05, 2010 2:02 PM To: Wittenberg, Kim (AHRQlCOE); Fitterman, Leslye (CMS/OCSQ)i Jacques, Louis B. (CMS/OCSQ)i Syrek Jensen, Tamara . S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: **Fridayat 1 PM: Scheduling Update Call for Provenge TA

Friday is not a good day since it is a flex day for some of u.s. Jarollins

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October 05, 2010 2:03 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); SyrekJensen, Tamara S. (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: **Friday at 1 PM: Scheduling Update Call for Provenge TA Importance: High

Good afternoon,

I'm having difficultly finding· a time for this call -- wou Id Friday at 1 pm ET work for you? Thank you in advance for letting me know this afternoon to help schedule this calll


2



From: Wittenberg, Kim (AHRQjCOE) Sent: Tuesday, October 05,2010 10:43 AM To: Wittenberg, Kim (AHRQ/COE); Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: 1 PM Deadline: DOODLE POLL Scheduling Update Call for Provenge TA

Good morning,

To facilitate scheduling this time-sensitive meeting. I've created a Doodle Poll. Please insert your availability into this poll by 1PM today.

Doodle link: http://doodle.com/participation.html?pollld=fuy56x2n36a7em5z


Kim Marie Wittenberg. MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639 E-mail: [email protected]

From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, October OS, 2010 9:43 AM To: Berliner, Elise (AHRQ); 'Mark, David'; 'Aronson, Naomi'; 'Flaherty, Sharon'; Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: 'Samson, David'; 'Sarsany, Lisa' Subject: *Response needed: Scheduling Update Call for Provenge TA Importance: High

Good morning,



3


Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality. Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639 E-mail: [email protected]

4


(b)(6)(b)(6)

(b)(6)(b)(6)(b)(6) (b)(6)

(b)(6)(b)(6)

(b)(6)


Dear Dr Fitterman,

I would appreciate some clarification on the provenge NCA. Is CMS considering not paying for the on label use ofprovenge, or is the NCA all about defining the on label population? The previous CMS communications on this matter are very unclear.

Thank you,

Dr SG Wilson

2



From: Wittenberg, Kim (AHRQ/COE) Sent: Wednesday, October 06,20104:07 PM To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Berliner, Elise (AHRQ)

Subject: Attachments:

**Provenge Prelim Draft** Preliminary T A sipuleucel T draft_1 0061 O.doc

Importance: High

Good afternoon,

Attached is a PRELIMINARY draft simply for discussion during Friday'S call. (The draft due date is not actually until the 13th, but we wanted to have a preliminary draft to review.)

, look forward t~ our call on Friday.

Thank you, Kim


From: Ziegler, Kathleen [mailto:[email protected] Sent: Wednesday, October 06, 2010 3:21 PM To: Sarsany, Lisa; Aronson, Naomi; Wittenberg, Kim (AHRQ/COE); Berliner, Elise (AHRQ); Mark, David Cc: DellaFave, Kimberly Subject:FW: Outcomes of Provenge

Elise and Kim:

Per Elise's email (following), attached is a PRELIMINARY draft of the outcomes of sipuleucel-T technology assessment (CANP0610) for your internal review. It is not in final format (e.g., not in the template), nor has it undergone final editing; however, it has been fact-checked and the tables have been integrated using 508-compliant formatting. This is being submitted for your internal review prior to Friday's meeting and should not be construed as representing the. final deliverable, which we are continuing to work on. .

Please let us know if you have any questions.

Regards,

Kathleen Kathleen M. Ziegler, Pharm.D. Director, Clinical Science Services Technology Evaluation Center (TEC) Blue Cross and Blue Shield Association

1



From: Berliner, Elise (AHRQ) [mailto:[email protected]] Sent: Tuesday, October 05, 2010 8:46 AM To: Sarsany, Lisa; Wittenberg, Kim (AHRQlCOE) Cc: Aronson, Naomi; Mark, David Subject: RE: Outcomes of Provenge

Lisa,

I think it would be good if you could send what you have by OCt. 6. Kim will set up a call with you and CMS to discuss next steps, we will need to decide whether we can finish peer review before the MedCAC. It would be VERY helpful to have your preliminary draft as we discuss this question.

Also, if you have FINAL tables in appendices etc. it would be good to send them, so that we can start converting to a format compliant with readers for the visually impaired (a requirement for gov't websites, but we are also seeing if we can get an exception for the draft report).

Thanks, Elise

-----------~~-.-.-------_._--"" From: Sarsany, Lisa [mailto:[email protected]] Sent: Monday, October 04, 2010 6:04PM To: Berliner, Elise (AHRQ); Wittenberg, Kim (AHRQlCOE) Cc: Aronson, Naomi; Mark, David Subject: Outcomes of Provenge

Hi Elise and Kim. We will be SUbmitting our Provenge report on October 12. We have consulted with a statistician who specializes in time-dependent confounding and are awaiting his report. We feel that his comments will be critical to understanding the role that postprogression docetaxel may have played in survival results as well as to issues of future research needs.

If you wish, we can share a preliminary draft on October 6, but it will not incorporate the statistical reviewer's report nor will it be fully edited. If you think this will be helpful, please let me know. Thank you. Best regards, Lisa

Lisa Sarsany Program Manager, Government Contracts Office of Clinical Affairs/TEC 312-297-5872 phone 312-297-5586 fax

2



From: Berliner, Elise (AHRQ) Sent: Thursday, October 07,2010 10:00 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); 'Mark, David'; 'Sarsany, Lisa'; 'Aronson, Naomi' Cc: Wittenberg, Kim (AHRQ/COE) Subject: RE: **Friday at 1 PM: Scheduling Update Call for Provenge TA

Call in number for the Provenge call, Friday at 1 p.m. eastern time.

Thanks everyone for being flexible in scheduling to allow this call to happen.

1-888-283-1134 Participant code: 172003#

Thanks, Elise

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12,20109:07 AM To: . Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: FW: new treatments for prostate cancer

FYI

From: Berliner, Elise (AHRQ) Sent: Tuesday, October 12, 2010 9:03 AM To: 'Mark, David'; Fitterman, Leslye (CMSjOCSQ); 'Sarsany,Lisa' Subject: new treatments for prostate cancer

Experimental Drug May Improve Survival In Men With Metastatic Castration-Resistant Prostate Cancer. The Wall Street Joumal (10/12, Winslow) reports that advanced prostate cancer patients have had limited treatment options. Now, however, on the heels of the Provenge (sipuleucel-T) and Jevtana (cabazitaxel) approvals, investigators are having success with an experimental treatment developed by Johnson & Johnson in which abiraterone acetate helped extend the life of patients with metastasized cancer.

Industry investors and the medical community became aware of the positive results last month after a monitoring committee said trial participants taking the placebo should now also be given the drug, according to Reuters (10/12, Hirschler). However, the degree of the trial's success only became publicly apparent on Monday.

The "research is part of the last of the three stages of testing usually needed for regulatory approval," Bloomberg News (10/12, Gibson) points out. "J&J, based in New Brunswick, New Jersey, may file new-drug applications in the US and Europe by the end of the year on the basis of the study results, the company said in a statement. "

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12, 20109:20 AM To: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: FW: new treatments for prostate cancer

FYI

From: Berliner, Elise (AHRQ) Sent: Tuesday, October 12, 2010 9: 15 AM To: Fitterman, Leslye (CMS/OCSQ) Subject: RE: new treatments for prostate cancer

And another news item:

Empire BCBS Posts Revised Coverage Policies/or ... Autologous Cellular Immunotherapy (or the Treatment o(Prostate Cancer

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12, 2010 9:07 AM To: Berliner, Elise (AHRQ) Subject: RE: new treatments for prostate cancer

Thanks Elise!

From: Berliner, Elise (AHRQ) Sent: Tuesday, October 12, 2010 9:03 AM To: 'Mark, David'; Fitterman, Leslye (CMS/OCSQ); 'Sarsany, Lisa' Subject: new treatments for prostate cancer

Experimental Drug May Improve Survival In Men With Metastatic Castration-Resistant Prostate Cancer. The Wall Street Journal (10112, Winslow) reports that advanced prostate cancer patients have had limited treatment options. Now, however, on the heels of the Provenge (sipuleucel-T) and Jevtana (cabazitaxel) approvals, investigators are having success with an experimental treatment developed by Johnson & Johnson in which abiraterone acetate helped extend the life of patients with metastasized cancer.

Industry investors and the medical community became aware of the positive results last month after a monitoring committee said trial participants taking the placebo should now also be given the drug, according to Reuters (10112, Hirschler). However, the degree of the trial's success only became publicly apparent on Monday.

The "research is part of the last of the three stages of testing usually needed for regulatory approval," Bloomberg News (10/12, Gibson) points out. "J&J, based in New Brunswick, New Jersey, may file new-drug applications in the US and Europe by the end of the year on the basis of the study results, the company said in a statement." .

1



From: . Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12, 2010 12:25 PM To: Berliner, Elise (AHRQ); Wittenberg, Kim (AHRQ/COE) Cc: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ) Subject: PROVENGE Draft TA

The PROVENGE draft TA may be posted on our website on November 10th if it is ready. We will note that AHRQ will post it on your website on November 17th for peer review.

Leslye

1



From: Berliner, Elise (AHRQ) Sent: Tuesday, October 12,201012:27 PM To: Fitterman, Leslye (CMS/OCSQ); Wittenberg, Kim (AHRQ/COE) Cc: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A.

(CMS/OCSQ) Subject: RE: PROVENGE Draft TA

Great thanks!!

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12, 2010 12:25 PM To: Berliner, Elise (AHRQ); Wittenberg, Kim (AHRQlCOE) Cc: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: PROVENGE Draft TA

The PROVENGE draft TA may be posted on our website on November 10th if it is ready. We will note that AHRQ will post it on your website on November 17th for peer review.

Leslye

1



From: Wittenberg, Kim (AHRQ/COE) Sent: Wednesday, October 13, 2010 3:20 PM To: Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ); Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, . Eileen (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) Subject: FW: CANP0610 "Outcomes of Sipuleucel-T Therapy" draft Attachments: CANP0610_0utcomes of Sipuleucel T_draft and appendixes_101310.doc

Good afternoon,

Attached is the CANP0610 (Provenge TA) draft. This just came in (and thus, we at AHRQ have not yet reviewed it), but I didn't want to delay sharing it with you. I'll set up a call to discuss this draft. Please let me know your availability next week,





540 Gaither Road,Room 6018

Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, October 14,20108:45 AM To: Rollins, James (CMS/OCSQ) Subject: RE: Question from BioCentury about Provenge NCA

Yes. Please see the answers following each question.

When can we expect a final decision from CMS about coverage of Provenge? By June 3eJ 21311 Will the proposed decision memo in March be a draft of that final coverage decision? Yes and we will solicit comments from interested parties for 313 days after the March 3eJ 21311 release of the draft document.

-----Original Message----From: Rollins J James (CMS/OCSQ) Sent: ThursdaYJ October 14J 213113 8:37 AM To: Fitterman J Leslye (CMS/OCSQ) Subject: FW: Question from BioCentury about Provenge NCA

Can you answer the questions below? Jarollins

-----Original Message----From: Schafer J Jyme H. (CMS/OCSQ) Sent: WednesdaYJ October 13 J 21310 6:131 PM To: Rollins J James (CMS/OCSQ) Subject: FW: Question from BioCentury about Provenge NCA

From: Brown-Jones J Shanterri M. (CMS/OCSQ) Sent: WednesdaYJ October 13 J 213113 3:54 PM To: Lund J Eleanor L. (CMS/OCSQ) Cc: Schafer J Jyme H. (CMS/OCSQ) Subject: FW: Question from BioCentury about Provenge NCA

Hi Ellie J

Can you please forward this inquiry through the appropriate channels in CAG?

Thanks

Shanterri Brown-Jones Correspondence Liaison Specialist Office of Clinical Standards and Quality Centers for Medicare &Medicaid Services Email: [email protected] Tel:410-786-6854 Fax:410-786-6857

From: CMS OEABox Sent: WednesdaYJ October 13J 20113 2:24 PM To: McLeod J Donald E. (CMS/OEA)

1


I ! !

Subject: FW: Question from BioCentury about Provenge NCA

From: Meredith Durkin [mailto:[email protected]] Sent: Wednesday~ October 13~ 2818 2:28 PM To: CMS OEABox Subject: Question from BioCentury about Provenge NCA

I wanted to verify the timeframe for the Provelige (autologous cellular immunotherapy' for the treatment of prostate cancer) NCA. The tracking sheet lists that a proposed dec.isiOri memo' is due March 30 and that the NCA will be complete June 38..

When can we expect a final deciSion from CMS about coverage of Provenge? Will the proposed decision memo in March be a draft of that final coverage decision?

Thank you~

Meredith Durkin BioCentury Publications 312-755-0798 x 251 [email protected]<mailto:[email protected]>.

Please send all press releases to: [email protected]<mailto:[email protected]>

1-.

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, October 14, 2010 9:47 AM To: Gulley, James (NIH/NCI) [E] Cc: Rollins, James (CMS/OCSQ); PASERCHIA~ LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: Presentation at the Novemverber 17th CMS MEDCAC

Dear Dr. Gulley:

Again, thank you for your willingness to participate at the November 17th meeting of Medicare Evidence Development and Coverage Advisory Committee as a guest speaker. We will be sending the panel members copies of all presentations, relevant peer-reviewed literature, practice guidelines,ect., next week. I apologize that we did not inform you earlier of this date. Therefore, please send me a copy of your slides for your talk on metastatic prostate cancer and the use of autologous cellular treatment for this condition by November 1, 2010.

Thank you in advance for your cooperation. Please call me if you have any questions.


Leslye Fitterman, PhD. Epidemiologist Centers for Medicare and Medicaid Services Office of Clinical Standards and Quality Coverage and Analysis Group 7500 Security Boulevard Cl-09-06 Fax - 410-786-9286 Phone - 410-786-1806 Email- [email protected]

1



From: Pencek, Eileen (CMS/OCSQ) Sent: Thursday, October 14, 20109:52 AM To: Wittenberg, Kim (AHRQ/COE) Cc: Fitterman, Leslye (CMS/OCSQ); Berliner, Elise (AHRQ); Rollins, James (CMS/OCSQ);

PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: CANP0610 "Outcomes of Sipuleucel-T Therapy" draft

Kim, I am available Monday-Thursday next week. Eileen Pencek

From: Wittenberg, Kim (AHRQlCOE) Sent: Wednesday, October 13, 20103:20 PM To: Fitterman, Leslye (CMSjOCSQ); Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Rollins, James (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ) Cc: Berliner, Elise (AHRQ) Subject: FW: CANP0610 "Outcomes of Sipuleucel-TTherapy" draft

Good afternoon,

Attached is the CANP061 0 (Provenge T A) draft. This just came in (and thus, we at AHRQ have not yet reviewed it). but I didn't want to delay sharing it with you. I'll set up a call to discuss this draft. Please let me know your availability next week.


Kim Marie Wittenberg,· MA




Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


1


Roliins, James (CMS/OCSQ)

From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, October 15, 2010 7:51 AM To: Rollins, James (CMS/OCSQ) Subject: RE: Nuegebauer letter to Berwick Attachments: Neugebauer letter to DMB 08242010.pdf; Neugebauer response 100410.docx; SUM-ADMIN

Neugebauer 101510.doc

Here are all the documents!

From: Rollins, James (CMS/OCSQ) Sent: Thursday, October 14, 20104:32 PM To: Fitterman, Leslye (CMS/OCSQ) Subject: FW: Nuegebauer letter to Berwick

Leslye, does Louis usually include a summary statement when respondingto requestors? Do you have any examples of summary statements that might be sent along with the response letter from Louis? Jarollins

From: Schafer, Jyme H. (CMS/OCSQ) Sent: Thursday, October 14, 2010 4:12 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) . Cc: Schiff, Pamela M. (CMS/OCSQ) Subject: RE: Nuegebauer letter to Berwick

Looks like this is DID

From: Schiff, Pamela M. (CMS/OCSQ) Sent: Thursday, October 14, 2010 2:05 PM To: Schafer, Jyme H. (CMS/OCSQ) Subject: FW: Nuegebauer letter to Berwick

Hi Jyme,

I received the Nuegebauer letter but not the summary statement. I need the summary statement as well. Can you please check with the analyst and forward to me today.

Thanks.

From: Schiff, Pamela M. (CMS/OCSQ) Sent: Thursday, October 14, 2010 11:14 AM To: Ashby, Lori M. (CMS/OCSQ) Subject: RE: Nuegebauer letter to Berwick

Hi Lori,

Can you please send me the summary statement?

Thanks.

1


From: Ashby, Lori M. (CMSjOCSQ) Sent: Tuesday, October OS, 2010 9:57 AM To: Brown-Jones, Shanterri M. (CMSjOCSQ); Schiff, Pamela M. (CMSjOCSQ) Subject: FW: Nuegebauer letter to. Berwick

Theresa will bring the folder to you momentarily.

Lori M. Ashby

Special Assistant OCSQ/Coverage and Analysis Group 410·7866322 [email protected]

Notice: The contents of thi.s message and any attachments may be privileged and confidential. Please do not disseminate without the approval of the Centers for Medicare &; Medicaid Services. If YOLI are not an intended recipient, or have received this me:ssage: in error, please delete it without reading it and please do not print, copy, forward, dissemi nate, or otherwise use the information. Also, pkase notify the: sender that you have received this communication in error. Your receipt of this message is l1L)t intended to waive any applicable pri\'ilcgc.

From: Fitterman, Leslye (CMSjOCSQ) Sent: Monday, October 04, 2010 4: 15 PM To: Ashby, Lori M. (CMSjOCSQ) Cc: Rollins, James (CMSjOCSQ) Subject: FW: Nuegebauer letter to Berwick

Lori:

Attached is the letter as approved by Louis.

Leslye

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, October 04, 2010 4: 14 PM To: Rollins, James (CMSjOCSQ) Cc: Fitterman, Leslye (CMSjOCSQ) Subject: RE: Nuegebauer letter to Berwick

Looks fine

2



From: Sent: To: Subject: Attachments:

Fitterman, Leslye (CMS/OCSQ) Friday, October 15, 2010 2:09 PM Rollins, James (CMS/OCSQ) CANP0610_0utcomes of Sipuleucel T _draft and appendixes-,-101310.doc CANP0610_0utcomes o~ Sipuleucel T_draft and appendixe(J01310.doc

1



From: Wittenberg, 'Kim (AHRQ/COE) Sent: Thursday, October 21,2010 1 :53 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Schott, Lawrence H.

(CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: FW: CMS Evidence Forum: provenge Attachments: CMS evidence forum pres~ntation provenge V2.pptx

! . . Good afternoon,

Attached are slides for the Provenge Evidence Forum.

Thanks, Kim





Rockville, MD 20850

Ph: 301-427-1488

Fax: 301-427-1639


From: Sarsany, Lisa [mailto:[email protected]] Sent: Wednesday, October 20, 2010 11:49 AM To: Berliner, Elise (AHRQ); Wittenberg, Kim (AHRQlCOE) Cc: Mark, David; Aronson, Naomi; Samson, David; Ziegler, Kathleen Subject: CMS Evidence Forum: Provenge

Elise and Kim, slides for David Mark's presentation to next week's Evidence Forum are attached. Please let me know if you have questions. Best, Lisa

Lisa Sarsany Program Manager, Government Contracts Office of Clinical Affairs/TEC 312-297-5872 phone 312-297-5586 fax

1


2



From: Wittenberg, Kim (AHRQ/COE) Sent: Monday, October 25, 2010 1:48 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B.

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) Subject: Request for approval/comments: CANP0610 Provenge Revised Draft Attachments: CANP061 O_Outcomes of Sipuleucel T_draft and appendixes_1 0251 0 REVISED.doc

Importance: High

Good afternoon, Attached is the revised draft for CANP0610 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for 508-compliance formatting. Thank you, Kim


1



From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, October 26,20107:45 AM To: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft

Thanks, Kim. Is it possible to give us the track-changes version so that I can expeditiously assess rather than have to plow through all 55 pages just to first find the revisions?

Thanks again.

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 418.786.2115 -----Original Message----

-From: Wittenberg, Kim (AHRQ/COE) Sent: Monday, October 25, 2818 1:48 PM To: Rollins, James (CMS/OCSQ)jFitterman, Leslye (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ)

ICc: Berliner, Elise (A~RQ) , I

Subject: Request for approval/comments: CANP8618 Prov~nge Revised Draft Importance: High

Good afternoon, Attached is the revised draft for CANP9618 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for s88-compliance formatting. Thank you, Kim


1



From: PASERCHIA, LORI A. (CMS/OCSQ)Sent: Tuesday, October 26,20107:45 AM To: Wittenberg, Kim (AHRQ/CO~); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); Jacques, LoUIs B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ);Pencek, Eileen (CMS/OCSQ)



Thanks again.

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 410.786.2115 -----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Monday,October 25, 2010 1:48 PM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: Request for approval/comments: CANP0610 Provenge Revised Draft Importance: High .

Good afternoon, Attached is the revised draft for CANP0610 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for 508-compliance

. formatting. Thank you, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 3e1~427-1639


1



From: Wittenberg, Kim (AHRQ/COE)Sent: Tuesday, October 26,20108:38 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ)'Pencek, Eileen (CMS/OCSQ) ,

Cc: Berliner, Elise (AHRQ)Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft Attachments: CANP0610 Provenge Compare,.docx

Good morning,

I've attached a compare document version to show the changes between the 10/13 version and yesterday's version. Please let me know if you have any questions.

Thank you,Kim .


-----Original Message----From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, October 26, 2010 7:45 AM. To: Wittenberg, Kim (AHRQ/COE)j Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j ~Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft


Thanks again.

Lori

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services Lori;[email protected] 410.786.2115 -----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Monday, October 25, 2010 1:48 PM To: Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OC~Q)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: Request for approval/comments: CANP0610 Provenge Revised Draft Importance: High

Good afternoon,

1


Attached is the revised draft for CANP0610 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for S08-compliance formatting .

. Thank you, Kim


2 . I

I


Rollins. James (CMSIOCSQ)

From: PASERCHIA,LORI A. (CMS/OCSQ)Sent: -Tuesday, October 26,201010:32 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)Subject: FW: Request for approval/comments: CANP0610 Provenge Revised Draft Attachments: CANP0610 Provenge Compare.docx

I don't see any significant reV1S10ns to content. Please give me a clue if I've missed something. Looks fine to me.

Lori A. Paserchia J MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 410.786.2115

>--,..--Original Message---->From: WittenbergJ Kim (AHRQ/COE) >Sent: TuesdaYJ October 26 J 2010 8:38 AM >To: PASERCHIAJ LORI A. (CMS/OCSQ)j Rollins J James (CMS/OCSQ)j >FittermanJ Leslye (CMS/OCSQ)j Jacques J Louis B. (CMS/OCSQ)j Syrek JensenJ Tamara S. >(CMS/OCSQ)j PencekJ Eileen (CMS/OCSQ) >Cc: BerlinerJ Elise (AHRQ) >Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft ' > >Good morningJ > >I've attached a compare document version to show the changes between >the >10/13 version and yesterday's version. Please let me know if you have >any questions. >/>Thank you J >Kim > >Kim Marie Wittenberg J MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road J Room 6018 Rockville J MD 20850 >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected] > > >-----Original Message---->From: PASERCHIAJ LORI A. (CMS/OCSQ) >Sent: TuesdaYJ October 26 J 2010 7:45 AM >To: Wittenberg J Kim (AHRQ/COE)j Rollins J James (CMS/OCSQ)j FittermanJ >Leslye (CMS/OCSQ)j Jacques J Louis B. (CMS/OCSQ)j Syrek Jensen J Tamara S. >(CMS/OCSQ)j Penc;ekJ Eileen (CMS/OCSQ) >Cc: BerlinerJ Elise (AHRQ) >Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft , ,

or.

> >ThanksJ Kim. Is it possible to give us the track-changes version so >that I can expeditiously assess rather than have to plow through all 55

1


>pages just to first find the revisions? > >Thanks again. > >Lori > >Lori A. Paserchia, MD >Coverage and Analysis Group >Centers for Medicare and Medicaid Services [email protected] >410.786.2115 >-----Original Message---->From: Wittenberg, Kim (AHRQ/COE) >Sent: Monday, October 25, 2010 1:48 PM >To: Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j Jacques, >Louis B. (CMS/OCSQ)j Syrek'Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, >LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ) >Subject: Request for approval/comments: CANP0610 Provenge Revised Draft >Importance: High > >Good afternoon, >Attached is the revised draft for CANP0610 (Provenge). Please let me >know if you have any comments. As soon as this is approved, I will >send it to our Web team for 508-compliance formatting. >Thank you, >Kim > > >Kim Marie Wittenberg, MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected]

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 26,201010:32 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, tORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: PROVENGE MEDCAC Questions Presentation Attachments: CMS presentation v1 LP rev.pptx

Jim:

Please review and provide comments on this presentation of the voting question that Lori will present at the MEDCAC meeting on November 17th. We are bound by the questions as they are shown in the document posted on the website.

Thanks in advance,

Leslye

1



From: Pencek, Eileen (CMS/OCSQ)Sent: Tuesday, October 26,201010:32 AM To: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)" Rollins James

(CMSlqCSQ) .. ' , Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft

agree

-----Original Message----From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, October 26, 2010 10:32 AM To: Fitterman, Leslye (CMS/OCSQ)jRollins, James (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Subject: FW: Request for approval/comments: CANP0610 Provenge Revised Draft

I don't see any significant revisions to content. Please give me a clue if I've missed something. Looks fine to me.

Lori A. Paserchia, MD Coverage and Analysis Group Centers for Medicare and Medicaid Services [email protected] 410.786.2115

>-----Original Message---->From: Wittenberg, Kim (AHRQ/COE) >Sent: Tuesday, October 26, 2010 8:38 AM >To: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); >Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. >(CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ) >Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft > >Good morning, > >I've attached a compare document version to show the changes between >the >10/13 version and yesterday's version. Please let me know if you have >any questions. > >Thank'you, >Kim > >Kim Marie Wittenberg, MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected] > > >-----Original Message---->From: PASERCHIA, LORI A. (CMS/OCSQ) >Sent: Tuesday, October 26, 2010 7:45 AM >To: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Fitterman,

1


>Leslye (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. >(CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ) >Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft > >Thanks, Kim. Is it possible to give us the track-changes version so >that I can expeditiously assess rather than have to plow through all 55 >pages just to first find the revisions? > >Thanks again. > >Lori > >Lori A. Paserchia, MD >Coverage and Analysis Group >Centers for Medicare and Medicaid Services [email protected] >410.786.2115 >- - - - -Original Me'ssage- - - - >From: Wittenberg, Kim (AHRQ/COE) >Sent: Monday, October 25, 2010 1:48 PM >To: Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j Jacques, >Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, >LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ) >Subject: Request for approval/comments: CANP0610 Provenge Revised Draft >Importance: High > >Good afternoon, >Attached is the revised draft for CANP0610 (Provenge). Please let me >know if you have any comments. As soon as this is approved, I will >send it to our Web team for Se8-compliance formatting. >Thank you, >Kim > > >Kim Marie Wittenberg, MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road, Room 6018 Rockville, MD 2e8Se >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected]

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 26,201010:34 AM To: PASERCHIA, LORIA. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek Eileen

(CMS/OCSQ) . ' Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft

I have found a few grammatical errors and some conclusions that may be worth re-stating in the "conclusions" or ~summary" section. But I am still reviewing it.

-----Original Message----From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Tuesday, October 26" 20U) 10: 32 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: FW: Request for approval/comments: CANP0610 Provenge .Revised Draft

I don't see any significant revisions to content. Please give me a clue if I've missed something. Looks fine to me.

Lori A. Paserchia, MD Coverage and Analysis GroupCenters for Medicare and Medicaid ServicesLori.Paserchia@~ms.hhs.gov

410.786.2115

>-----Original Message---->From: Wittenberg, Kim (AHRQ/COE)

. >$ent: Tuesday, October 26, 2010 8:38 AM >To: PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); >Fitterman, Leslye (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. >(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ)>Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft > >Good morning, >>I've attached a compare document version to show the changes between >the >10/13 version and yesterday's version. Please let me know if you have >any questions. > >Thank you, >Kim > >Kim Marie Wittenberg, MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected] > > >-----Original Message----~

>From: PASERCHIA, LORI A. (CMS/OCSQ) >Sent: Tuesday, October 26, 2010 7:45 AM

1


>To: Wittenberg, Kim (AHRQ/COE)j Rollins, James (CMS/OCSQ)j Fitterman, >Leslye (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. >(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (AHRQ) >Subject: RE: Request for approval/comments: CANP0610 Provenge Revised >Draft > >Thanks, Kim. Is it possible to give us the track-changes version so >that I can expeditiously assess rather than have to plow through all 55 >pages just to first find the revisions? > >Thanks again. > >Lori > >Lori A. Paserchia, MD >Coverage and Analysis Group >Centers for Medicare and Medicaid Services [email protected] >410.786.2115 >-----Original Message---->From: Wittenberg, Kim (AHRQ/COE) >Sent: Monday, October 25, 2010 1:48 PM >To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Jacques, >Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, >LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) >Cc: Berliner, Elise (At-IRQ) >Subject: Request for approval/comments: CANP0610 Provenge Revised Draft >Importance: High > >Good afternoon, >Attached is the revised draft for CANP0610 (Provenge). Please let me >know if you have any comments. As soon as this is approved, I will >send it to our Web team for 508-compliance formatting. >Thank you, >Ki,m > > >Kim Marie Wittenberg, MA >Agency for Healthcare Research and Quality Center for Outcomes and >Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 >Ph: 301-427-1488 >Fax: 301-427-1639 >E-mail: [email protected]

2



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 26,201012:14 PM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions Presentation

The powerpoint program does not recognize "generalizable" as a word. The underline does not appear on the slides when printed and I have deleted the underline. Thanks - I'll send it to Maria now.

From: Rollins, James (CMS/OCSQ) Sent: Tuesday, October 26,2010 12:00 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: RE: PROVENGE MEDCAC Questions Presentation

The presentation look fine, but the word generalizable is underlined in the last few slides. Jarollins

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 26,2010 10:32 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: PROVENGE MEDCAC Questions Presentation

Jim:

Please review and provide comments on this presentation of the voting question that Lori will present at the MEDCAC meeting on November lih. We are bound by the questions as they are shown in the document posted on the website.

Thanks in advance,

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ)Sent: Friday, October 29, 2010 8:41 AM To: Wittenberg, Kim (AHRQ/COE); Rollins,James (CMS/OCSQ); Jacques, Louis B. .

(CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ);Pencek, Eileen (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft Attachments: CANP0610 Provenge Compare LF notes.docx

Kim:

Attached is the document with my comments for consideration by David and the BCBS team.

Thanks, Leslye

-----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Monday, October 25, 2010 1:48 PM To: Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: Request for approval/comments: CANP0610 Provenge Revised Draft Importance: High

Good afternoon, Attached is the revised draft for CANP0610 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for s08-compliance formatting. Thank you, Kim


1



From: Sent: To: Cc:


Barry,

Attached re Marilyn email.

Louis

Jacques, Louis B. (CMS/OCSQ) Friday, October 29,20104:11 PM Straube, Barry M. (CMS/OCSQ); Andrews, Danielle Y. (CMS/OCSQ) Ashby, Lori M. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins,.James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Provenge 2 pager LBJ tsj102910 (2).docx Provenge 2 pager LBJ tsj102910 (2).docx

1



From: Wittenberg, Kim (AHRQ/COE)Sent: Friday, October 29,20109:09 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Jacques, Louis B.

(CMS/OC~Q); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ)'Pencek, Eileen (CMS/OCSQ) ,


Great! Thank you, Leslye!

Sincerely, Kim


-----Original Message----From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, October 29, 2010 8:41 AM To: Wittenberg, Kim (AHRQ/COE)j Rollins, James (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: RE: Request for approval/comments: CANP0610 Provenge Revised Draft

Kim:

Attached is the document with my comments for consideration by David and the BCBS team.

Thanks, Leslye

-----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Monday, October 25, 2010 1:48 PM To: Rollins, James (CMS/OCSQ)j Fitterman, Leslye (CMS/OCSQ)jJacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Berliner, Elise (AHRQ) Subject: Request for approval/comments: CANP0610 Provenge Revised Draft Importance: High

Good afternoon, Attached is the revised draft for CANP0610 (Provenge). Please let me know if you have any comments. As soon as this is approved, I will send it to our Web team for 508-compliance formatting. Thank you, Kim

1



2



From: Ellis, Maria A. (CMS/OCSQ) Sent: Monday, November 01,201011:22 AM To: Jacques, Louis B. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: FW: January 19, 2011 MEDCAC Meeting Attachments: FR Notice 01 19 2011.doc

Good Morning!

Attachedfor your review/clearance is the FR Noticefor the January J9'h

MEDCAC meeting onESAs. The ifl:formation highlighted in green isfor webinar registration and will be replaced. Upon your approval it will be sent forwardfor agency clearance.

Health Insurance Specialist Division ofOperations andlnfonnation Management Coverage andAiJalysis Group,. OCSQ (410) 786-0309

[email protected]

From: Long, Kimberly A. (CMS/OCSQ) Sent: Thursday, October 14, 2010 1:20 PM To: Rollins, James (CMS/OCSQ) Cc: Ellis, Maria A. (CMS/OCSQ) Subject: RE: January 19, 2011 MEDCAC Meeting

Jim,

Please review the attached FR notice for the ESA MEDCAC.

Thanks, Kim

From: Ellis, Maria A. (CMS/OCSQ) Sent: Tuesday,October 12, 2010 1:40 PM To: Long, Kimberly A. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: January 19, 2011 MEDCAC Meeting

Good Aflernoon!

1


Attached is the fiR J..Votice and disclosure statement.jor the ujJcorning January 1 fjlt MI~DCACMeeting. I have inputted qll the dates and other required ir?jormation, please replace the yellow highlighted in.fi)rm,ation with yourrrleeting language and return the document to rne. l)lease let rne kno'w ifyou Ita've any questions.

Ilcaili] Il1surancc Spcdali'il . DivisioIl of" OpcratioIls aJl(lIn/orIniIlion MalliJbFCmCIll

C'oVCTJgC il11(J Analysis Group~ O{,:SYQ (410) 786-030.9

[email protected]

2



From: Ellis, Maria A. (CMS/OCSQ)Sent: Monday, November 01, 2010 11 :24 AM To: Jacques, Louis B. (CMS/OCSQ)Cc: Rollins, James (CMS/OCSQ) Subject: FW: January 19, 2011 MEDCAC Meeting Attachments: Disclosure Statement January 19 2011.doc

Good Morning!

Attachedjor your review/clearance is the disclosure slatenuntjor the January 1gil MEDCAC tneeting on E~SAs. Upon your. approval it will be sent.fiJr'ward jor agency clearance.

Healdl hlsurallcc Spcciali'it DivisioIl oIOperatiolls alld illlormatioIlM;U1agclllcnl G'ovcrJgc alld Analysis Group, OC~Q (410) 786-030.9

[email protected]

From: Long, Kimberly A. (CMS/OCSQ) Sent: Thursday, October 14, 2010 1:28 PM To: Rollins, James (CMS/OCSQ) Cc: Ellis, Maria A. (CMS/OCSQ) Subject: RE: January 19, 2011 MEDCAC Meeting

Jim,

Please review the attached MEDCAC disclosure statement.

Thanks, Kim

From: Ellis, Maria A. (CMS/OCSQ) Sent: Tuesday, October 12, 2010 1:40 PM To: Long, Kimberly A. (CMS/OCSQ) Cc:Roilins, James (CMS/OCSQ) Subject: January 19, 2011 MEDCAC Meeting

Good Afternoon!

1


Attached is lhe FR Notice and disclosure staternent jiJr the upconling January 19th MJ~D('~C Meeting. I have inputted all the dates and other required i I

information, please replace the yellow highlighted inforrnation with your rfweting language and return the docurnent to rfle. l>lease let rne kno'w t!you have any questions.

Ileallll hlSIlTaIlCe Speciali'tt DiyisioIl ofOperations and III/ormation Management Coverage andAniJiysi't Group, OC5Q (410) 786~O/J0.9

[email protected]

2



From: Gulley, James (NIH/NCI) [E] [[email protected]] Sent: Monday, November 01, 2010 12:17 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: RE: Presentation at the Novemverber 17th CMS MEDCAC Attachments: 2010 11 17 MEDCAC rev2.ppt; MEDCAC Prostate Cancer Overview Gulley.pdf

Thanks so much. I made the slight changes in the slides we discussed this am. Attached are a PDF version and the Power Point version. I don't know how you disseminate this to the committee but thought the PDF version might be best.

Please let me know if you have additional questions or concerns.

James

James L. Gulley, M.D., Ph.D., F.A.C.P. Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, October 14, 2010 9:47 AM To: Gulley, James (NIH/NCI) [E] Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ) Subject: Presentation at the Novemverber 17th CMS MEDCAC

Dear Dr. Gulley:

Again, thank you for your willingness to participate at the November 17th meeting of Medicare Evidence Development and Coverage Advisory Committee as a guest speaker. We will be sending the panel members copies,of all presentations, relevant peer-reviewed literature, practice guidelines, ect., next week. I apologize that we did not inform you earlier of this date. Therefore, please send me a copy of your slides for your talk on metastatic prostate cancer and the use of autologous cellular treatment for this condition by November I, 2010.



Leslye Fitterman, PhD. Epidemiologist

1


Centers for Medicare and Medicaid Services Office of Clinical Standards and Quality Coverage and Analysis Group 7500 Security Boulevard C1-09-06 Fax - 410-786-9286 Phone - 410-786-1806 Email- [email protected]

2



From: Pencek, Eileen (CMS/OCSQ) Sent: Monday, November 01,20103:05 PM To: Berliner, Elise (AHRQ); Fitterman, Leslye (CMS/OCSQ); Wittenberg, Kim (AHRQ/COE) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: PROVENGE Draft TA

Hi Elise, Just confirming that the Provenge Draft TA will come to us 508 compliant for our November 10th posting.

Thanks, Eileen Pencek

From: Berliner, Elise (AHRQ) Sent: Tuesday, October 12, 2010 12:27 PM To: Fitterman, Leslye (CMS/OCSQ); Wittenberg, Kim (AHRQ/COE) Cc: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: PROVENGE Draft TA

. Great thanks!!

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, October 12, 2010 12:25 PM To: Berliner, Elise (AHRQ); Wittenberg, Kim (AHRQ/COE) Cc: Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: PROVENGE Draft TA

The PROVENGE draft TA may be posted on our website on November 10th if it is ready.· We will note that AHRQ will post

it on your website on November lth for peer review.

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 01, 2010 1 :00 PM To: Gulley, James (NIH/NCI) [E]; Ellis, Maria A. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ) Subject: RE: Presentation at the Novemverber 17th CMS MEDCAC

Thank you James. Maria here is the final version of the slides Dr. Gulley will present at the November 17,2010 MEDCAC.

From: Gulley, James (NIH/NCI) [E] [mailto:[email protected]] Sent: Monday, November 01, 2010 12:17 PM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ)i Pencek, Eileen (CMS/OCSQ)i Ellis, Maria A. (CMS/OCSQ) . Subject: RE: Presentation at the Novemverber 17th CMS MEDCAC

Thanks so much. I made the slight changes in the slides we discussed this am. Attached are a PDF version and the Power Point version. I don't know how you disseminate this to the committee but thought the PDF version might be best.

Please let me know if you have additional questions or concerns.

James

James L. Gulley~ M.D' J Ph.D.~ F.A.C.P. Director J Clinical Trials Group, Laboratory of Tumor Immunology and Biology &Principal Investigator, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health 10 Center Dr. 13N208, MSC-1750 Bethesda, MD 20892


webpage: <http://ccr.cancer.gov/Staff/Staff.asp?StaffID=517> Clinical Trials: http://bethesdatrials.cancer.gov/investigator-profiles!gulley!default.asp MOB Website: http://medicaloncology.cancer.gov!

From: Fitterman, Leslye (CMS!OCSQ) Sent: Thursday, October 14,-2010 9:47 AM To: Gulley, James (NIH/NCI) [E] Cc: Rollins, James (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ)i Pencek, Eileen (CMS/OCSQ)i ElliS, Maria A. (CMS/OCSQ) Subject: Presentation at the Novemverber 17th CMS MEDCAC

Dear Dr. Gulley:

Again, thank you for your willingness to participate at the November 17th meeting of Medicare Evidence Development and Coverage Advisory Committee as a guest speaker. We will be sending the panel members copies of all presentations, relevant peer-reviewed literature, practice guidelines, ect., next week. I apologize that we did not

1


inform you earlier of this date. Therefore, please send me a copy of your slides for your talk on metastatic prostate cancer and the use of autologous cellular treatment for this condition by November 1, 2010.



Leslye Fitterman, PhD. Epidemiologist Centers for Medicare and Medicaid Services Office ofClinical Standards and Quality Coverage and Analysis Group 7500 Security Boulevard Cl-09-06 Fax - 410-786-9286 Phone - 410-786-1806 Email - [email protected]

2



From: Jacques, Louis B. (CMS/OCSQ) Sent: Thursday, November 04, 2010 1:46 PM To: Rollins, James (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Ellis, Maria A.

(CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ) Subject: Re: November 17th MEDCAC Documents

Agenda ok. But we should hold off on the roster til the Monday before Sent from my Blackberry

From: Rollins, James (CMSjOCSQ) Sent: Thursday, November 04, 201001:03 PM To: Jacques, Louis B. (CMSjOCSQ) Subject: FW: November 17th MEDCAC Documents

Louis here is the agenda and roster for your approval for posting. Jarollins

From: Ellis, Maria A. (CMSjOCSQ) Sent: Thursday, November 04, 2010 10:53 AM To: Rollins, James (CMSjOCSQ) Subject: November 17th MEDCAC Documents

Good Morning!

Attachedfor your reviewlclearance.for dUj)lication and 'loeb posting are the agenda, speakers list and roster.

Heald] Insur:mce Speciali51 DjVl:~:ioll o[Opcralions and Infi:)lmatioll MaIlagclllclll C'OVL'Idfj"C alldAllalys.i., (;rol1P~ OCS'Q (410) 786..030.9

[email protected]

1


Rollins, James (CMS/OCSQ) \

From: Wittenberg, Kim (AHRQ/COE) Sent: Friday, November 05, 2010 11 :23 AM To: Wittenberg, Kim (AHRQ/COE); Fitterman, Leslye (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Cc: Berliner, Elise (AHRQ) Subject: FW: Slides for Prevenge MCAC Attachments: MCAC presentation.ppt

Importance: High

Good morning, Attached are the revised Provenge slides for the upcoming MedCAC. Thank you, Kim

From: Sarsany, Lisa [[email protected]] Sent: Friday, November 05,2010 11:09 AM To: Ziegler, Kathleen; Wittenberg, Kim (AHRQ/COE)

. Subject: FW: Slides for MCAC

fyi

Lisa Sarsany Program Manager, Government Contracts Technology Evaluation Center BlueCross BlueShield Association 312-297-5872 phone 312-297-5586 fax

From: Mark, David Sent: Friday, November OS, 2010 10:07 AM To: 'Berliner, Elise (AHRQ)' Cc: Arenson, Naomi; Sarsany, Lisa Subject: Slides for MCAC

Final version of slides attached. David M.

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From: PASERCHIA, LORI A. (CMS/OCSQ) Sent: Monday, November 08,20107:42 AM To: Fitterman, Leslye(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: washpost: provenge

http://www.washingtonpost.com/wp-dyn/content/articie/2010/11/07/AR201011070S20S.html?hpid=topnews

/

.1


Rollins, James. (CMS/OCSQ)

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, November OB, 2010 B:41 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

PASERCHIA, LORI A. (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: FW: Post on Provenge

Team,

FYI. Issue is handled. Please do not speak to outsiders who may try to contact you. You already have the 2 pager.

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, November 08,20107:24 AM To: Ashkenaz, Peter (CMSjOEABS) Cc: Syrek Jensen, Tamara S. (CMSjOCSQ) Subject: Re: Post on Provenge

We sent danielle a 2 pager last wk Sent from my Blackberry

From: Ashkenaz, Peter (CMSjOEABS) Sent: Monday, November 08, 201007:19 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ) Cc: Anderson, Kelly (CMSjOCSQ); Andrews, Danielle Y. (CMSjOCSQ); Khalid, Aryana C. (CMSjOA); McLeod, Donald E. (CMSjOEA) Subject: RE: Post on Provenge

Those letters are exactly what we need, but it did show up on Page 1 so I expect other folks to be calling and asking for background as well as needing something for Don's hearing next week. If you think we need to send a letter - no more than 150 words,- we can get something cleared and have Barry submit it.

Also, I'm working from home today, so sort of around.

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, November 08,20107:07 AM To: Ashkenaz, Peter (CMSjOEABS); Syrek Jensen, Tamara S. (CMS/OCSQ); Ashby, Lori M. (CMSjOCSQ) Cc: Anderson, Kelly (CMSjOCSQ); Andrews, Danielle Y. (CMSjOCSQ); Khalid, Aryana C. (CMSjOA); McLeod, Donald E. (CMSjOEA) Subject: Re: Post on Provenge

Peter

The article is moronic. They are simply wrong and just speculating. We have cleared language we've been using in our Congressional letters explaining why we opened. And I spoke with SFC minority staff last week via OL.

Louis Sent from my Blackberry

From: Ashkenaz, Peter (CMSjOEABS)· Sent: Monday, November 08, 2010 06:53 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ)

1


Cc: Anderson, Kelly (CMS/OCSQ); Andrews, Danielle Y. (CMS/OCSQ)i Khalid, Aryana C. (CMS/OA); McLeod, Donald E. (CMS/OEA) Subject: Post on Provenge

Folks - we're going to need some quick talkers to prepare higher ups no later than lOAM today. Most importantly - is thie review due to health reform and the Administration efforts to contain costs?

I know we were going to try to put Barry onthe phone with him, I don't know whathappened.

Review of prostate cancer drug Provenge renews medical cost-benefit

debate

By Rob Stein Washington Post Staff Writer Monday, November 8, 2010; 12:30 AM

Federal officials are conducting an unusual review to detennine whether the government should pay for an expensive new vaccine for treating prostate cancer, rekindling debate over whether some therapies are too costly.

The Centers for Medicare & Medicaid Services, which dictate what treatments the massive federal healthinsurance program for the elderly will cover, is running a "national coverage analysis" dfProvenge, the first vaccine approved for treating any cancer. The treatment costs $93,000 a patient and has been shown to extend patients' lives by about four months.

Although Medicare is not supposed to take cost into consideration when making such rulings, the decision to launch a fonnal examination has raised concerns among cancer experts, drug companies, lawmakers, prostate cancer patients and advocacy groups.

Provenge, which was approved for advanced prostate cancer in April, is the latest in a series of new high-priced cancer treatments that appear to eke out only a few more months of life, prompting alarm about their cost.

"This absolutely is the opening salvo in the drive to save money in the health-care system," said Skip· Lockwood, who heads Zero - the Project to End Prostate Cancer, a Washington-based lobbying group. "lfthe cost wasn't a consideration, this wouldn't even be under discussion."

Those concerns have been heightened because the review comes after the bitter health-care refonn debate, which was marked by accusations about rationing and "death panels." The appointment of Donald M. Berwick to head Medicare only intensified anxieties. President Obama sidestepped a Senate battle by naming Berwick, who has advocated for scrutinizing costs, when Congress was in recess in July.

Because men tend to be elderly when they get diagnoses of advanced prostate cancer, Medicare's decision will have a major effect on Provenge's availability. Regional Medicare providers paying for Provenge would have to . stop. Private insurers also tend to follow Medicare's lead.

Medicare officials, who are convening a panel of outside advisers to vet the issue at a public hearing Nov. 17, say Provenge's price tag isn't an issue. But Berwick and other officials declined to discuss the rationale for the reVIew.

"Certainly no one in the Medicare program would publicly state that the price tag would have anything to do with Medicare looking at it. But they are human beings, too. They notice things like that," said Sean Tunis,

2


director of the Center for Medical Technology Policy and a former chief medical officer at Medicare. Tunis said, though, that other factors, such as the special nature of the therapy and lingering questions about its effectiveness, were probably playing a more crucial role.

The review comes as the Food and Drug Administration considers withdrawing an approval for another expensive cancer treatment - A vastin for metastatic breast cancer - which triggered a similar debate even though the FDA too is not supposed to factor costs into its analyses.

Medicare usually covers new cancer drugs once they have been approved by the FDA. The decision in June to scrutinize Provenge prompted several members ofCongress to question the action. Supporters have inundated the agency with hundreds of thousands of comments.

"I don't want to blarrie Obamacare, but it just kind of figures that people are taking a look at what the costbenefit ratios are and all that sort of stuff," said David Dykes, 69, of Lorton, a retired federal employee who was hoping to try Provenge. "That may sound pretty good to the people who want to cut costs, but it doesn't sound too good to me. This is something that could extend my life. I'd like to give that a shot."

Some fear the move will discourage pharmaceutical companies from developing new cancer drugs.

"It is extremely chilling if, after spending a huge sum of money, time and effort to get a drug through FDA approval, you'll then have to go through it all again to see ifCMS will pay for it," said Allen S. Lichter, head of the American Society of Clinical Oncology. "Firing a shot across the bow like this is not the way to have an intelligent and meaningful discussion about how we start to address the complex issue of drug costs."

Provenge has long been the center of controversy. The FDA delayed Provenge's approval in 2007. The rejection triggered outrage among patients, advocates and investors in Dendreon, the Seattle company that developed Provenge. The campaign to win Provenge's approval included anonymous death threats, accusations of conflicts of interest, protests, congressional lobbying and vitriolic Internet postings.

Prostate cancer strikes 192,000 men in the United States each year and kills about 27,000. The only therapies are surgery, radiation, hormones and the chemotherapy drug Taxotere.

Unlike standard vaccines, which are given before someone gets sick to stimulate their immune system to fight off infections, Provenge is a "therapeutic vaccine," designed to attack cancer cells in the body.

To produce Provenge, doctors remove immune system cells from patients, expose the cells in the laboratory to a protein found on most prostate cancer cells and an immlll1e system ~timulator, and infuse the cells back into the patient in a month-long series of three treatments. In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months.

"To charge $90,000 for four months, which comes out to $270,00 for a year of life, I think that's too expensive," said Toto Fojo of the National Cancer Institute. "A lot of people will say, 'It's my $100,000, and it's my four months.' Absolutely: A day is worth $1 million to some people. Unfortunately, we can't afford it as a society."

Others agreed, especially given the modest benefit.

"I'd like to think cost doesn't need to come up when it's a slam dunk," said H. Gilbert Welch ofthe Dartmouth Institute for Health Policy and Clinical Practice. "But when it's a close call1ike this, it certainly has to be a factor. That's $100,000 Medicare can't spend elsewhere."

But such commentary has caused widespread alarm among patients and advocates. 3


"The men most impacted by prostate cancer are African American men. If eMS doesn't approve this, then this treatment becomes an exclusive kind of treatment for men who can afford it out of pocket," said Thomas .Farrington, president of the Prostate Health Education Network.

Others stressed that many men live far longer on the treatment and that even four months is extremely valuable to some.

"Whenever you are faced with a disease where you can lose your life, you really would like to extend it as much as you can," said Leibel B. Harelik, 61, a prostate cancer patient who is executive director of the Prostate Cancer Resource Center in Austin.

Company officials say the cost is not out of line with that of other cancer drugs. Each treatment With Provenge, whichthe company estimates cost nearly $1 billion to develop, is tailored to each patient.

"Because of that, we have higher costs associated with this product," said Mitchell H. Gold, Dendreon's chief executive. "Provenge is a unique new medicine that prolongs the lives of patients with late-stage prostate cancer. These patients need access to innovative new medicines."

Whatever the outcome on Provenge, many on both sides agreed that more debate over other new high-tech therapies was likely to come.

"At some point, if we keep paying these very high prices fortreatments that provide very limited benefit; we're going to reach the point where we can no longer afford health care," said Alan Garber, a professor of medicine and economist at Stanford University. "Some say we're living through that right now."

4



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 08, 2010 8:46 AM To: Ellis; Maria A. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James

(CMS/OCSQ) Subject: FW: TA Report and Presentation November 17 2010 Attachments: MCAC T A presentation.ppt; Final_Outcomes of Sipuleucel T _draft_appendices11 021 O.doc

Forgot attachments

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 08,20108:37 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: TA Report and Presentation November 172010

Maria:

Please find attached the draft report and slides for the November 17th MedCAC.

Leslye

1



From: Schafer, Jyme H. (CMS/OCSQ) Sent: Monday, November 08,20109:16 AM To: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ) Subject: . provenge post article

http://www.washingtonpost.com/wp-dyn/content/articie/2010/11/07/AR2010110705205.html

Jyme H. Schafer, MD, MPH Director, Division of Medical and Surgical Services CMS/OCSQjCoverage and Analysis Group 7500 Security Blvd. Mallstop CI-09-06 Baltimore, MD 21244

410-786-4643

1



From: Pencek,' Eileen (CMS/OCSQ) .Sent: Monday, November 08,20109:59 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ellis, Maria A.

(CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: T A Report and Presentation November 17 2010

Leslye, This may seem a little picky, but I think David's slide presentationTitle page should read "Medicare Evidence Development and Coverage Advisory Committee" rather than "Medicare Coverage Advisory Committee" Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 08, 20108:37 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: TA Report and Presentation November 17 2010

Maria:

Please find attached the draft report and slides for the November 17th MedCAC.

Leslye

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 08,201010:04 AM To: Pencek, Eileen (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ellis, Maria A.

(CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: TA Report and Presentation November 17 2010

I agree, but since he incorporated very few of our suggestions I am okay with leaving it as it is.

From: Pencek, Eileen (CMS/OCSQ) Sent: Monday, November 08,20109:59 AM To: Fitterman, Leslye (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Subject: RE: TA Report and Presentation November 172010

Leslye,

This may seem a little picky, but I think David's slide presentation Title page should read "Medicare Evidence Development and Coverage Advisory Committee" rather than "Medicare Coverage Advisory Committee" Eileen

From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 08,20108:37 AM To: Ellis, Maria A. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: TA Report and Presentation November 17 2010

Maria:

Please find attached the draft report and slides for the November lth MedCAC.

Leslye

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, November 08,201010:48 AM To: Andrews, Danielle Y. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Anderson, Kelly (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) .

Subject: RE: Information needed on Provenge Attachments: Provenge Talking Points.docx

Here ya go~ let me know if they need more. Cobbled together from past documents

-----Original Message----From: Andrews~ Danielle Y. (CMS/OCSQ) Sent: Monday~ November 88~ 2818 18:31 AM To: Jacques~ Louis B. (CMS/OCSQ); Syrek Jensen~ Tamara S. (CMS/OCSQ) Cc: Anderson~ Kelly (CMS/OCSQ) Subject: FW: Information needed on Provenge

Hi Louis and Tamara-

I know you both have responded to Peter regarding the Provenge article; however~ OA is now requesting background talking points about the NCD process and the specific process for Provenge to OS as soon as possible. Could you send me this information? Thanks so much.

Danielle

>-----Original Message---->From: Lewis~ Caya B. (CMS/OA) >Sent: Monday, November 88~ 2818 18:25 AM >To: Straube~ Barry M. (CMS/OCSQ)· >Cc: LaPan~ Jarel (HHS/IOS); Berwick~Donald (OA); Tavenner~ Marilyn >(CMS/OA); Andrews~ Danielle Y. (CMS/OCSQ); Miller~ Ruth A. (CMS/OA) >Subject: Information needed onProvenge > >There is an article in the Washington Post regarding Provenge that has >caught both Bill and the Secretary's attention. > >We need to get some background information on the our NCD process and >the specific process for Provenge to Jarel (for Bill and the Secretary) as soon as possible. > >Barry and I are in a senior staff meeting now~ but I am hoping that >Danielle and Sam can get someone from OCSQ working on this right away. >Can you please let me know if that is possible or if we need to pull Barry from our meeting? > >Thanks~

> >Caya

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, November 08, 2010 10:48 AM To: Andrews, Danielle Y. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Anderson, Kelly (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ)

Subject: RE: Information needed on Provenge Attachments: Provenge Talking Points.docx

Here ya go, let me know if they need more. ~ Cobbled together from past documents

-----Original Message----From: Andrews, Danielle Y. (CMS/OCSQ) Sent: Monday, November 08, 2010 10:31 AM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Anderson, Kelly (CMS/OCSQ) Subject: FW: Information needed on Provenge

Hi Louis and Tamara-

I know you both have responded to Peter regarding the Provenge article; however, OA is now requesting background talking points about the NCD process and the specific process for Provenge to OS as soon as possible. Could you send me this information? Thanks so much.

Danielle

>-----Original Message---->From: Lewis, Caya B. (CMS/OA) >Sent: Monday, November 08, 2010 10:25 AM >To: Straube, Barry M. (CMS/OCSQ) >Cc: LaPan, Jarel (HHS/IOS); Berwick, Donald (OA); Tavenner, Marilyn >(CMS/OA) ; Andrews, Danielle Y. (CMS/OCSQ); Miller, Ruth A., (CMS/OA) >Subject: Information needed on Provenge > >There is an ~rticle in the Washington Post regarding Provenge that has >caught both Bill and the Secretary's attention. > >We need to get some background information on the our NCD process and >the specific process for Provenge to Jarel (for Bill and the Secretary) as soon as possible. > >Barry and I are in a senior staff meeting now, but I am hoping that >Danielle and Sam can get someOne from OCSQ working on this r:i:ght away. >Can you please let me know if that is possible or·if we need to pull Barry from our meeting? > >Thanks, > >Caya

1



From: Stieber, Joan (CMS/OL) Sent: Monday, November 08,201012:11 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Schafer, Jyme H. (CMS/OCSQ); Griffith, Ellen B. (CMS/OEA); Ashkenaz, Peter (CMS/OEABS); Hall, Amy (CMS/OL); Clapton, Erin M. (CMS/OL); Burney, Ira (CMS/OL); Martino, Maria(CMS/OL); Hunt, Rebecca J. (CMS/OL); Leung, Isabella (CMS/OL)

Subject: Washington Post article: Review of prostate cancer drug Provenge renews medical costbenefit debate

In case you haven't seen this already, there's a front page article in today's Washington Post about the Provenge coverage analysis (pasted in below FYI). I am particularly disturbed by the first sentence's assertion that this is "an unusual review". Ih fact, as we (and Louis) have recently explained to several Congressional inquirers, initiation of an NCD review in cases of contractor variation is quite routine.

The 7th paragraph also seems carelessly drafted insaying: "Because men tend to be elderly when they get diagnoses of advanced prostate cancer, Medicare's decision will have a major effect on Provenge's availability. Regional Medicare providers paying for Provenge would have to stop. Private insurers also tend to follow Medicare's lead./I- seeming to suggest that a non-coverage decision is expected.

The article focuses almost entirely on cost as opposed to effectiveness questions, and suggests a differential racial impact.

No current CMS official is directly quoted in the article - did the author even bother to contact CMS?

thanks - Joan in OL

Review of prostate cancer drug Provenge renews medical cost-benefit debate

By Rob Stein Washington Post Staff Writer Monday, November 8,2010; 7:52 AM

Federal officials are conducting to determine whether the govemment should pay for an expensive new vaccine for treating prostate cancer, rekindling debate over whether some therapies are too costly.

The Centers for Medicare & Medicaid Services, which dictate what treatments the massive federal healthinsurance program for the elderly will cover, is running a "national coverage analysis" of Provenge, the first vaccine approved for treating any cancer. The treatment costs $93,000 a patient and has been shown to extend patients' lives by about four months.

Although Medicare is not supposed to take cost into consideration when making such rulings, the decision to launch a formal examination has raised concems among cancer experts, drug companies, lawmakers, prostate cancer patients and advocacy groups.

, Provenge, which was approved for advanced prostate cancer in April, is the latest in a series of new high-priced : cancer treatments that appear to eke out only a few more months of life, prompting alarm about their cost.

1


"This absolutely is the opening salvo in the drive to save money in the health-care system," said Skip Lockwood, who heads Zero - the Project to End Prostate Cancer, a Washington-based lobbying group. "lfthe cost wasn't a consideration, this wouldn't even be under discussion."

Those concerns have been heightened because the review comes after the bitter health-care reform debate, which was marked by accusations about rationing and "death panels." The appointment ofDonald M. Berwick to head Medicare only intensified anxieties. President Obama sidestepped a Senate battle by naming Berwick, who has advocated for scrutinizing costs, when Congress was in recess in July.

Because men tend to be elderly when they get ~~~~no~~s.?f ad;~~.ce~ pr.o~tate~~cer,~~dicar~'s;.deci~~~n will have a major effect on Provenge's availability. Bl~.~J;?NIII~"~~~III~~i"'~;uglllnl~iIliJ~[~;~Q

Private insurers also tend to follow Medicare's lead.


"Certainly no one in the Medicare program would publicly state that the price tag would have anything to do with Medicare looking at it. But they are human beings, too. They notice things like that," said Sean Tunis, director of the Center for Medical Technology Policy and a former chief medical officer at Medicare. Tunis said, though, that other factors, such as the special nature of the therapy and lingering questions about its effectiveness, were probably playing a more crucial role.

The review comes as the Food and Drug Administration considers withdrawing an approval for another expensive cancer treatment- Avastin for metastatic breast cancer - which triggered a similar debate even though j

the FDA too is not supposed to factor costs into its analyses.

Medicare usually covers new cancer drugs once they have been approved by the FDA. The decision in June to scrutinize Provenge prompted several members of Congress to question the action. Supporters have inundated the agency with hundreds of thousands of comments.

"I don't want to blame Obamacare, but it just kind of figures that people are taking a look at what the costbenefit ratios are and all that sort of stuff," said David Dykes, 69, of Lorton, a retired federal employee who was ) hoping to try Provenge. "That may sound pretty good to the people who want to cut costs, but it doesn't sound· too good to me. This is something that could extend my life. I'd like to give that a shot."

Some fear the move will discourage pharmaceutical companies from developing new cancer drugs.

"It is extremely chilling if, after spending a huge sum of money, time and effort to get a drug through FDA approval, you'll then have to go through it all again to see ifCMS will pay for it," said AllenS. Lichter, head of the American Society of Clinical Oncology. "Firing a shot across the bow like this is not the way to have an intelligent and meaningful discussion about how we start to address the complex issue of drug costs."

Provenge has long been the center of controversy. The FDAdelayed Provenge's approval in 2007. The rejection, triggered outrage among patients, advocates and investors in Dendreon, the Seattle company that developed Provenge. The campaign to win Provenge's approval included anonymous death threats, accusations of conflicts' of interest, protests, congressional lobbying and vitriolic Internet postings.


2


' i

, . .

Unlike standard v~ccin~s, which are given before someone gets sick to stimulate their immune system to fight . off infections, Provenge is a "therapeutic vaccine," designed to attack cancer cells in the body.

To produce Provenge, doctors remove immune system cells from patients, expose the cells in the laboratory to a protein found on most prostate cancer cells and an immune system stimulator, and infuse the cells back into the patient in a month-long series of three treatments. In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months.

"To charge $90,000 for four months, which comes out to $270,00 for a year oflife, I think that's too expensive," said Tito Fojo of the National Cancer Institute. "A lot of people will say, 'It's my $100,000, and it's my four· months.' Absolutely: A day is worth $1 million to some people. Unfortunately, we can't afford it as a society."


"I'd like to think cost doesn't need to come up when it's a slam dunk," said H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice. "But when it's a close call like this, it certainly has to be a" factor. That's $1 00,000 Medicare can't spend elsewhere."

, But such commentary has caused widespread alJrm among patients andkdvocates.

If CMS doesn't approve this, then this treatment becomes an exclusive kind of treatment for men who can afford it out of pocket," said Thomas Farrington, president of the Prostate Health Education Network.



Company officials say the cost is not out of line with that of other cancer drugs. Each treatment with Provenge, which the company estimates cost nearly $1 billion to develop, is tailored to each patient.

"Because of that, we have higher costs associate~ with this product," said Mitchell H. Gold, Dendreon's chief executive. "Provenge is a unique new medicine that prolongs the lives of patients with late-stage prostate cancer. These patients need access to innovative new medicines."


"At some point, if we keep paying these very high prices for treatments that provide very limited benefit, we're going to reach the point where we can no longer afford health care," said Alan Garber, a professor of medicine and economist at Stanford University. "Some say we're living through that right now."

3


Rollins, James (CMS10CSQ)

From: Ashkenaz, Peter (CMS/OEABS) Sent: Monday, November 08,201012:14 PM To: Stieber, Joan (CMS/OL); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ); Rollins, James (CMS/OCSQ); Schafer, Jyme H. (CMS/OCSQ); Griffith, Ellen B. (CMS/OEA); Hall, Amy (CMS/OL); Clapton, Erin M~ (CMS/OL); Burney, Ira (CMS/OL); Martino, Maria (CMS/OL); Hunt, Rebecca J. (CMS/OL); Leung, Isabella (CMS/OL)

Subject: Re: Washington Pos.t article: Review of prostate cancer drug Provenge renews medical costbenefit debate

Yes, Don Mcleod worked with the reporter, but he only wanted an intervieW with Dr. Berwick.

Please forgive any errors, this was sent using BlackBerry

From: Stieber, Joan (CMSjOL) Sent: Monday, November 08,2010 12:11 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen,Tamara S. (CMSjOCSQ); Rollins, James (CMSjOCSQ); Schafer, Jyme H. (CMSjOCSQ); Griffith, Ellen B.(CMSjOEA); Ashkenaz, Peter (CMSjOEABS); Hall, Amy (CMSjOL); Clapton, Erin M. (CMSjOL); Burney, Ira (CMSjOL); Martino, Maria (CMSjOL); Hunt, Rebecca J. (CMSjOL); Leung, Isabella (CMSjOL) Subject: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

In case you haven't seen this already, there's a front page article in today's Washington Post about the Provenge coverage analysis (pasted in below FYI). I am particularly disturbed by the first sentence's assertion that this is "an unusual review". In fact, as we (and Louis) have recently explained to several Congressional inquirers, initiation of an NCD review in cases of contractor variation is quite routine.

The 7th paragraph also seems carelessly drafted in saying: "Because men tend to be elderly when they get diagnoses of advanced prostate cancer, Medicare's decision will have a major effect on Provenge's availability. Regional Medicare providers paying for Provenge would have to stop. Private insurers also tend to follow Medicare's lead." - seeming to suggest that a non-coverage decision is expected.


No current CMS official is directly quoted in the article - did the author even bother to contact eMS?

, thanks - Joan in OL


By Rob Stein Washington Post SfaffWriter Monday, November 8, 2010; 7:52 AM

Federal officials are conducting to determine whether the government should pay for an expensive new vaccine for treating prostate cancer, rekindling debate over whether some therapies are too costly.

1



Although Medicare is not supposed to take cost into consideration when making such rulings, the decision to launch a formal examination has raised concerns among cancer experts, drug companies, lawmakers, prostate "cancer patients and advocacy groups.

Provenge, which was approved for advanced prostate cancer in April, is the latest in a series of new high-priced cancer treatments that appear to eke out only afew more months oflife, prompting alarm about their cost.

"This absolutely is the opening salvo in the drive to save money in the health-care system," said Skip Lockwood, who heads Zero - the Project to EndProstate Cancer, a Washington-based lobbying group. "If the cost wasn't a consideration, this wouldn't even be under discussion."

Those concerns have been heightened because the review comes after the bitter health-care reform debate, which was marked by accusations about rationing and "death panels." The appointment of Donald M. Berwick to head Medicare only intensified anxieties. President Obama sidestepped a Senate battle by naming Berwick, who has advocated for scrutinizing costs, when Congress was in recess in July.

Because ~en tend to be elderly when !he~ ?et di~~i~~s ?r~g0~i~~f~?~~i:~,e can~~~;7~ei~~~~i~i:~~fi~i,?~i+~11~\1ft have a major effect on Provenge's aVailabIlIty. ~g!~IIl~~a!~i~;!ProVt~ffl~g~{!il~0~.~'~'P~~!1111~b



"Certainly no one in the Medicare program would publicly state that the price tag would have anything to do with Medicare looking at it. But they are human beings, too. They notice things like that," said Sean Tunis, director of the Center for Medical Technology Policy and a former chief medical officer at Medicare. Tunis said, though, thatother factors, such,as the special nature of the therapy and lingering questions about its effectiveness, were probably playing a more crucial role.

The review comes as the Food and Drug Administration considers withdrawing an approval for another expensive cancer treatment- Avastin for metastatic breast cancer- which triggered a similar debate even though the FDA too is not supposed to factor costs into its analyses.

Medicare usually covers new cancer drugs once they have been approved by the FDA. The decision in June to scrutinize Provenge prompted several members of Congress to question the action. Supporters have inundated the agency with hundreds of thousands of comments.

"I don't want to blame Obamacare, but it just kind of figures that people are taking a look at whatthe costbenefit ratios are and all that sort of stuff," said David Dykes, 69, of Lorton, a retired federal employee who was . hoping to try Provenge. "That may sound pretty good to the people who want to cut costs, but it doesn't sound too good to me. This is something that could extend my life. I'd like to give that a shot."

Some fear the move 'will discourage pharmaceutical companies from developing new cancer drugs.

2


"It is extremely chilling if, after spending a huge sum of money, time and effort to get a drug through FDA approval, you'll then have to go through it all again to see if CMS will pay for it," said Allen S. Lichter, head of the American Society of Clinical Oncology. "Firing a shot across the bow like this is not the way to have an intelligent and meaningful discussion about how we startto address the complex issue of drug costs."



Unlike standard vaccines, which are given before someone gets sick to .stimulate their immune system to fight off infections, Provenge is a "therapeutic vaccine," designed to attack cancer cells in the body.

To produce Provenge, doctors remove immune system cells from patients, expose the cells in the laboratory to a protein found on most prostate cancer cells and an immune system stimulator, and infuse the cells back into the patient in a month-long series of three treatments. In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months.

"To charge $90,000 for four months, which comes out to $270,00 for a year of life, I think that's too expensive," said Tito Fojo of the National Cancer Institute. "A lot of people will say, 'It's my $100,000, and it's my four months.' Absolutely: A day is worth $1 million to some people. Unfortunately, we can't afford it as a society."


"I'd like to think cost doesn't need to come up when it's a slam dunk," said H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice. "But when it's a close call like this, it certainly has to be a factor. That's $100,000 Medicare can't spend elsewhere."

But such commentary has caused widespread alarm among patients and advocates.

If CMS doesn't approve this, then this treatment becomes an exclusive kind of treatment for men who can afford it out of pocket," said Thomas Farrington, president ofthe Prostate Health Education Network.


"Whenever you are faced with a disease where you can lose your life, you really would like to extend it as much ' as you can," said Leibel B. Harelik, 61, a prostate cancer patient who is executive director of the Prostate Cancer Resource Center in Austin.

Company officials say the cost is not out of line with that of other cancer drugs. Each treatment with Provenge, which the company estimates cost nearly $1 billion to develop, is tailored to each patient.

"Because of that, we have higher costs associated with this product," said Mitchell H. Gold, Dendreon's chief executive. "Provenge is a unique new medicine that prolongs the lives of patients with late-stage prostate cancer. These patients need access to innovative new medicines."

3


Whatever the outcpme on Provenge,'many on both sides agreed that more debate over other new high-tech therapies was likely to come.

"At some point, ifwe keep paying these very high prices for treatments that provide very limited benefit, we're going to reach the point where we can no longer afford health care," said Alan Garber, a professor ofmedicine and economist at Stanford University. "Some say we're living through that right now."

4



From: Jacques, louis B. (CMS/OCSQ) Sent: Monday, November 08,201012:16 PM To: Stieber, Joan (CMS/Ol); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Schafer, Jyme H. (CMS/OCSQ); Griffith, Ellen B. (CMS/OEA); Ashkenaz, Peter (CMS/OEABS); Hall, Amy (CMS/Ol); Clapton, Erin M. (CMS/Ol); Burney, Ira (CMS/Ol); Martino, Maria (CMS/Ol); Hunt, Rebecca J. (CMS/Ol); leung, Isabella (CMS/Ol)

Subject: Re: Washington Post article: Review of prostate cancer drug Provenge renews medical costbenefit debate

Joan

Already disc with Peter A. The article is just plain wrong.

Louis Sent from my Blackberry

From: Stieber, Joan (CMS/Ol) Sent: Monday, November 08, 2010 12:11 PM To: Jacques, louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Schafer, Jyme H. (CMS/OCSQ); Griffith, Ellen B. (CMS/OEA); Ashkenaz, Peter (CMS/OEABS); Hall, Amy (CMS/Ol); Clapton, Erin M. (eMS/Ol); Burney, Ira (CMS/Ol); Martino, Maria (CMS/Ol); Hunt, Rebecca J. (CMS/Ol); leung, Isabella (CMS/Ol) Subject: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

In case you haven't seen this already, there's a front page article in today's Washington Post about the Provenge coverage analysis (pasted in below FYI). I am particularly disturbed by the first sentence's assertion that thisis "an unusual review". In fact, as we (and Louis) have recently explained to several Congressional inquirers, initiation ofan NCD review in cases of contractor variation is quite routine.

The ih paragraph also seems carelessly drafted in saying: "Because men tend to be elderly when they get diagnoses of advanced prostate cancer, Medicare's deCision will have a major effect on Provenge's availability. Regional Medicare providers paying forProvenge would have to stop. Private insurers also tend to follow Medicare's lead." - seeming to suggest that a non-coverage decision is expected.



thanks - Joan in OL


By Rob Stein Washington Post Staff Writer Monday, November 8, 2010; 7:52 AM

1


Federal officials are conducting to determine whether the government should pay for an expensive new vaccine for treating prostate cancer, rekindling debate over whether some therapies are too costly.


Although Medicare is not supposed to take cost into consideration when making such rulings, the decision to launch a formal examination has raised concerns among cancer experts, drug companies, lawmakers, prostate cancer patients and advocacy groups.

Provenge, which was approved for advanced prostate cancer in April, is the latest in a series of new high-priced cancer treatments that appear t() eke out only a few more months oflife, prompting alarm about their cost.

"This absolutely is the opening salvo in the drive to save moneyin the health-care system," said Skip Lockwood, who heads Zero - the Project to End Prostate Cancer, a Washington-based lobbying group. "If the cost wasn't a consideration, this wouldn't even be under discussion."

Those concerns h,ave been heightened because the review comes after the bitter health-care reform debate, which was marked by accusations about rationing and "death panels." The appointment of Donald M. Berwick to head Medicare only intensified anxieties. President Obama sidestepped a Senate battle by naming Berwick, who has advocated for scrutinizing costs, when Congress was in recess in July.

Because men tend to be elderly when they get dia~no~7~ of~dy~ncedpr9~~~~ecat,J:~er'.Medicare's decision will have a major effect on Provenge's availability. B-egt~I.Med[r~l:provtj~l~~payiilllrrl



"Certainly no one in the Medicare program would publicly state that the price tag would have anything to do with Medicare looking at it. But they are human beings, too. They notice things like that," said Sean Tunis, director of the Center for Medical Technology Policy and a former chief medical officer at Medicare. Tunis said, though, that other factors, such as the special nature of the therapy and lingering questions about its effectiveness, were probably playing a more crucial role.

The review comes as the Food and Drug Administration conSiders withdrawing an approval for another expensive cancer treatment- Avastin for metastatic breast cancer - which triggered a similar debate even though the FDA too is not supposed to factor costs into its analyses.

Medicare usually covers new cancer drugs once they have been approved by the FDA. The decision in June to scrutinize Provenge prompted several members of Congress to questi~n the action. Supporters have inundated the agency with hundreds ofthousands of comments.

"I don't want to blame Obamacare, but it just kind of figures that people are taking a look at what the costbenefit ratios are and all that sort of stuff," said David Dykes, 69, of Lorton, a retired federal employee who was • hoping to try Provenge. "That may sound pretty good to the people who want to cut costs, but it doesn't sound too good to me. This is something that could extend my life. I'd like to give that a shot."

2


Some fear the move will discourage pharn1aceutical companies from developing new cancer drugs.

"It is extremely chilling if, after spending a huge sum of money, time and effort to get a drug through FDA approval,you'll then have to go through it all again to see ifCMS will pay for it," said Allen S. Lichter, head of the American Society of Clinical Oncology. "Firing a shot across the bow like this is not the way to have an intelligent and meaningful discussion about how we start to address the complex issue of drug costs."



Unlike standard vaccines, which are given before someone gets sick to stimulate their immune system to fight offinfections,'Provenge is a "therapeutic vaccine," designed to attack cancer cells in the body.

, To produce Provenge, doctors remove immune system cells from patients, expose the cells in the laboratory to a protein found on most prostate cancer cells and an immune system stimulator, and infuse the cells back into the patient in a month-long series of three treatments. In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months.

"To charge $90,000 for four months, which comes out to $270,00 for a year oflife, I think that's too expensive," . said Tito Fojo of the National Cancer Institute. "A lot of people will say, 'It's my $100,000, and it's my four months.' Absolutely: A day is worth $1 million to some people. Unfortunately, we can't afford it as a society."


"I'd like to think cost doesn't need to come up when it's a slam dunk," said H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice. "Butwhen it's a close call like this, it certainly has to be a factor. That's $100,000 Medicare can't spend elsewhere.'" '

But such commentary has caused widespread alarm among patients and advocates.

If CMS doesn't approve this, then this treatment becomes an exclusive kind of treatment for men who can afford it out of pocket," said Thomas Farrington, president ofthe Prostate Health Education Network.



Company officials say the cost is not outofline with that of other cancer drugs. Each treatment with Provenge, which the company estimates cost nearly $1 billion to develop, is tailored to each patient.

3

I


"Because of that, we have higher costs associated with this product," said Mitchell H. Gold, Dendreon's chief executive. "Provenge is a unique new medicine that prolongs the lives of patients with late-stage prostate cancer. These patients need access to i1l1lovative new medicines."


"At some point, if we keep paying these very high prices for treatments that provide very limited benefit, we're going to reach the point where we can no longer afford health care," said Alan Garber, a professor of medicine and economist at Stanford University. "Some say we're living through that right now."

4



From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 09,20108:20 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Jacques, Louis B.


Cc: Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: READY FOR MEDCAC POSTING: CANP0610 Provenge 508-compliant draft Attachments: CANP0610_0utcomes_SipuleuceLT_draft_REV_110210.pdf

Importance: High

Good morning,

Attached is the 508-compliant Provenge draft which is ready for posting on the MedCAC Web page.

Thank you, Kim


1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, November 09,20108:21 AM To: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Jacques, Louis B.


Cc: Dolina, Elaine L (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: RE: READY FOR MEDCACPOSTING: CANP0610 Provenge 508-compliant draft

Thank you Kim. I will initiate our clearing process for posting. Leslye

--~--Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 09, 2010 8:20 AM To: Fitterman, Leslye (CMS/OCSQ)j Rollins, James (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) j Manlovej- John (CMS/OCSQ) j Berliner, Elise (AHRQ) Subject: READY FOR MEDCAC POSTING: CANP0610 Provenge 508-compliant draft Importance: High

" . :'iGood morning,

Attached is the 508-compliant Provenge draft which is ready for posting on the MedCAC Web page.

Thank you,' Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center.for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-1488 Fax: 301-427-1639 E-mail: [email protected]

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, November 09, 2010 8:29 AM To: Rollins, James (CMS/OCSQ) Cc: Pencek, Eileen (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ) Subject: FW: READY FOR MEDCAC POSTING: CANP0610 Provenge 508-compliant draft Attachments: CANP0610_0utcomes_SipuleuceLT_draft_REV_11 021 O.pdf

Importance: High

Jim:

TheTA for the MEDCAC meeting is attached for your approval and finally Louis's approval so that Elaine may post it tomorrow. It is now 588 compliant. When it is posted on the CMS Coverage website the following should be included as per the request from AHRQ.

The Agency for Healthcare Research and Quality will post this document on its' website for review and comments from the public on November 17, 2818.

Leslye

-----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 89, 2818 8:28 AM To: Fitterman, Leslye (CMS/OCSQ)j Rollins, James (CMS/OCSQ)j Jacques, louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ)j Manlove, John (CMS/OCSQ)j Berliner, Elise (AHRQ) Subject: READY FOR MEDCAC POSTING: CANP8618 Provenge S88-compliant draft Importance: High

Good morning,

Attached is the S88-compliant Provenge draft which is ready for posting on the MedCAC Web page.

Thank you, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 548 Gaither Road, " Room 6818 Rockville, MD 28858 Ph: 381-427-1488 Fax: 381-427-1639 E-mail: [email protected]

1



From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 09, 2010 8:30 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Jacques, Louis B.


Cc: Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner; Elise (AHRQ) Subject: RE: READY FOR MEDCAC POSTING: CANP0610 Provenge 508-compliant draft

Great! Thank you, Leslie!

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301-427-148S Fax: 301-427-1639 E-mail: [email protected]

-----Original Message----From: Fitterman, Lesly,e (CMS/OCSQ) Sent: Tuesday, November 09, 2010 8:21 AM To: Wittenberg, Kim (AHRQ/COE); Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: RE: READY FOR MEDCAC POSTING: CANP0610 Provenge 50S-compliant draft

Thank you Kim. I will initiate our clearing process for posting. Leslye

-----Original Message----From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 09, 2010 S:20 AM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: READY FOR MEDCAc POSTING: CANP0610 Provenge 50S-compliant' draft Importance: High

Good morning,

Attached is the 50S-compliant Provenge draft which is ready for posting on the MedCAC Web page.

Thank you, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 601S Rockville, MD 20SS0 Ph: 301-427-1488 Fax: 301~427-1639


1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 09,20108:37 AM To: Wittenberg, Kim (AHRQ/COE); Fitterman, Leslye (CMS/OCSQ); Rollins, James

(CMS/OCSQ); Syrek Jepsen, Tamara S. (CMS/OCSQ); PASERCHIA, LORI A (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Cc: Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Berliner, Elise (AHRQ) Subject: Re: READY FOR MEDCAC POSTING: CANP0610 Provenge 508-compliant draft

After 4 tomorrow Wednesday ok to post Sent from my Blackberry

Original Message ----From: Wittenberg, Kim (AHRQ/COE) Sent: Tuesday, November 09, 2010 08:19 AM To: Fitterman, Leslye (CMS/OCSQ)j Rollins, James (CMS/OCSQ)j Jacques, Louis B. (CMS/OCSQ)j Syrek Jensen, Tamara S. (CMS/OCSQ)j PASERCHIA, LORI A. (CMS/OCSQ)j Pencek, Eileen (CMS/OCSQ) Cc: Dolina, Elaine L. (CMS/OCSQ) j Manlove, John (CMS/OCSQ) j Berliner, Elise (AHRQ) Subject: READY FOR MEDCAC POSTING: CANP0610 Provenge S08-compliant draft

Good morning,

Attached is the S08-compliant Provenge draft which is ready for posting on the MedCAC Web page.

Thank you, Kim

Kim Marie Wittenberg, MA Agency for Healthcare Research and Quality Center for Outcomes and Evidence 540 Gaither Road, Room 6018 Rockville, MD 20850 Ph: 301~427-1488

Fax: 301-427-1639 E-mail: Kim;[email protected]

1


(b)(6)

(b)(6)(b)(6)(b)(6)


Office of Clinical Standards and Quality

Coverage and Analysis Group

7500 Security Boulevard

CI-09-06

Fax - 410-786-9286

Phone - 410-786-1806

Email - [email protected] "I

i

2



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 09,201012:30 PM To: Stieber, Joan (CMS/OL) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Leung, Isabella

(CMS/OL); Clapton, Erin M. (CMS/OL); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Subject: Re: Further Questions on Provenge

1. FDA noted stroke risk in the label. Provengefailed first two clinical trials.

2. Provenge represents a new class of therapy.

3. False. See NCD for abarelix.

4. Coverage is by case by case at contractor level. The current appearance of consistency is because contractors are waiting for the NCD and held off noncovering. Dendreon fails to appreciate that opening the NCD pre empted local noncoverage. It is disingenuous to claim that current situation reflects late June reality.

5. Advance notice is not required for NCD opening. We have never seen evidence of a ems leak. Dendreon never followed up their claims. We cannot control outside speculation.

Sent from my Blackberry

From: Stieber, Joan (CMS/OL) Sent: Tuesday, November 09, 2010 12:04 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye(CMS/OCSQ); Clapton, Erin M. (CMS/OL); Leung, Isabella (CMS/OL); Martino,Maria (CMS/OL) Subject: Further Questions on Provenge

Good morning. I just had a chat with Tony Clapsis (Senate Finance Democratic staff) about arguments being raised on the Hill by the Provenge manufacturer (Dendreon) and advocates, which the Committee staff would like our help in responding to. Tony predicts this issue is only going to get hotter and more politicized, and they want to be able to help put it in better perspective.

Here are 5 arguments being made about why CMS' actions are inappropriate (with perhaps an underlying implication that we are therefore motivated by cost?):

(1) CMS has never before reviewed an oncology product this quickly after FDA approval, before any problems were demonstrated.

(2) CMS has never cOl)vened a MEDCAC on a single product (as opposed to a type or class of products).

(3) In the past, CMS has only looked at off-label use of cancer products, not on-label use.

(4)14 ofthe 15 MACs are now covering Provenge, so variation across contractors (claimed by CMS as a reason forthe 1:

NCA) is minimal.

1


(5) Concern has also been raised about the timing and nature of communication from CMS - e.g., Dendreon believes they had insufficient notice of the opening of the NCA, while leaks before the NCA was announced adversely affected Dendreon stock.

In addition, Tony notes (for our information) a general strategy of trying to blur fines between CMS and FDA, suggesting that CMS is really re-opening the FDNs "safe and effective" determination.

Tony would appreciate a further conference call with Louis et al. to discuss these questions. I checked Louis' and Tamara's on-line calendars and it looks like you're both out today and tomorrow but that Friday this week (11/12) might work, is that correct? If so, is there a time that would be most convenient for you?

Also, in the interim, if you have any quick responses to the questions above, please feel free to send them to methanks!

-- Joan

From: Stieber, Joan (CMSjOL) [mailto:[email protected]] Sent: Friday, November 05, 2010 4:49 PM To: Clapsis, Tony (Finance-Dem) Cc: Dawe, Chris (Finance-Dem); Clapton, Erin M. (CMS10L) Subject: Re: Provenge ...

Hi Tony. You had asked for some examples of other NCDs (besides Provenge) that were initiated because of differences across contractors. Please forgive our delay in getting back to you.

We checked with Dr. Louis Jacques, Director of CMS'Coverage &Analysis Group, and he noted that NCDs are frequently requested due to local coverage variation, which indicates disagreement in the medical community about the scientific evidence. If the contractors all agree on coverage policy, there is generally no need for an NCD.

Here are a few examples where local variability was prominent, along with links to information on the CMS Coverage webpage (some of these were based on external requests; others were initiated by CMS):

• Allogeneic Stem Cell Transplant for MDS (http://www . cms. gov /mcd/viewnca .asp ?where=index&nca id=238&basket=nca: ee415N:~238 : Alloge neic+Hematopoietic+Stem+Cell+Transplantation+%28HSCT%29+for+Myelodysplastic+Syndrome:Cl osed:New:12)

• Blood brain barrier disruption chemotherapy (http://www.cms.gov[mcd/viewnca.asp?where=index&nca id=188&basket=nca:BB333N:188:Blood+ Brain+Barrier+Disruption+%28BBBD%29+Chemotherapy:Closed:New:13)

• Microvolt T wave alternans (http://www.cms.gov/mcd/viewtrackingsheet.asp?id=213)

• Nesiritide for Heart Failure (in this case, coverage varied even within a single city because hospitals could nominate their own FI contractor) (http://www.cms.gov!mcd!viewnca.asp?where=index&nca id=163&basket=nca:0B289N:163:Nesiri tide+for+Treatment+of+Heart+Failure+Patients:Closed:New:24)

• CT Angiography (http://www.cms.gov/mcd/viewnca.asp?from=basket&nca id=206&viewAMA=N&basket=nca%3A00385 : N%3A206%3AComputed+Tomographic+Angiography%3AClosed%3ANew%3A15)

2


I hope this information is helpful. ·If you have any further questions, please let us know.

-~ Joan

Joan Stieber, CMS Office of Legislation (202) 690-6884 / [email protected]

From: Clapsis, Tony (Finance-Oem) [mailto:[email protected]] Sent: Thursday, October 28, 2010 11:38 AM To: Clapton, Erin M. (CMS/OL) Cc: Oawe, Chris (Finance-Oem) Subject: Provenge ...

Hey Erin)

We had a call a while back (August?) on the NCA on Provenge, and had asked for some followup.

I believe it was examples of where there may have been conflicts In local coverage decisions, which we talked about as one of the key reasons behind the NCA. Can we try and get those back next week?

May have some additional questions and need for a followup c~ll after that.

Thanks, Tony

Tony Clapsis Senate Finance Committe 202-224-4608

3



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 09,201012:30 PM To: Stieber, Joan (CMS/OL) . .

Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Leung, Isabella Cc: (CMS/OL); Clapton, Erin M.(CMS/OL); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Subject: Re: Further Questions on Provenge

1. FDA noted stroke risk in the label. Provenge failed first two clinical trials.



4. Coverage is by case by case at contractor level. The current appearance of consistency is because contractors are waiting for the NCD and held off noncovering. Dendreon fails to appreciate that opening the NCD pre empted local noncoverage. It is disingenuous to claim that current situation reflects late June reality.

5. Advance notice is not required for NCD opening. We have never seen evidence of a cms leak. Dendreon never followed up their claims. We cannot control outside speculation.


From: Stieber, Joan (CMSjOL) Sent: Tuesday, November 09, 2010 12:04 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMSjOCSQ); Clapton, Erin M. (CMS/OL); Leung, Isabella (CMSjOL); Martino, Maria (CMSjOL) Subject: Further Questions on Provenge



(1) CMS has never before reviewed an oncology product this quickly after FDA approval, before any problems were demonstrated.

(2) CMS has never convened a MEDCAC on a single product (as opposed to a type or class of products).


(4) 14 of the 15 MACs are now covering Provenge, so variation across contractors (claimed by CMS as a reason for the NCA) is minimal.

1



In addition, Tony notes (for our information) a general strategy of trying to blur lines between CMS and FDA, suggesting that CMS is really re-opening the FDA's "safe and effective" determination.

Tony would appreciate a further conference call with louis et al. to discuss these questions. I checked louis' and Tamara's on-line calendars and it looks like you're both out today and tomorrow but that Friday this week (1l/12) might work, is that correct? If so, is there a time that would be most convenient for you?

Also,in the interim, if you have any quick responses to the questions above, please feel free to send them to methanks!

-- Joan

From: Stieber, Joan (CMSjOL) [mailto:[email protected]] Sent: Friday, November 05, 2010 4:49 PM To: Clapsis, Tony (Finance-Oem) Cc: Oawe, Chris (Finance-Oem); Clapton, Erin M. (CMSjOL) Subject: Re: Provenge ...


We checked with Dr. louis Jacques, Director of CMS' Coverage & Analysis Group, and he noted that NCDs are frequently requested due to local coverage variation, which indicates disagreement in the medical community about the scientific evidence. If the contractors all agree on coverage policy, there is generally no need for an NCD.


• Allogeneic Stem Cell Transplant for MDS (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=238&basket=nca:00415N:238:Alloge neic+Hematopoietic+Stem+Cell+Transplantation+%28HSCT%29+for+Myelodysplastic+Syndrome:Cl osed:New:12)

• Blood brain barrier disruption chemotherapy (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=188&basket=nca:00333N:188:Blood+ Brain+Barrier+Disruption+%28BBBD%29+Chemotherapy:Closed:New:13)


• Nesiritide for Heart Failure (in this case, coverage varied even within a single city because hospitals could nominate their own FI contractor) (http://www.cms.gov!mcd/viewnca.asp?where=index&nca id=163&basket=nca:00289N:163:Nesiri tide+for+Treatment+of+Heart+Failure+Patients:Closed:New:24)

• CT Angiography (http://www.cms.gov/mcd/viewnca.asp?from=basket&nca id=206&viewAMA=N&basket=nca%3A00385 N%3A206%3AComputed+Tomographic+Angiography%3AClosed%3ANew%3A15)

2


I hope this information is helpful. If you have any further questions, please let us know.

-- Joan

Joan Stieber, CMS Office of legislation (282) 698-6884 / [email protected]

From: Clapsis, Tony (Finance-Dem) [mailto:[email protected]] Sent: Thursday, October 28, 2818 11:38 AM To: Clapton, Erin M. (CMS/Ol) Cc: Dawe, Chris (Finance-Dem) Subject: Provenge .•.

Hey Erin,


I believe it was examples of where there may have been conflicts In local coverage decisions, which we talked about as one of the key reasons behind the NCA. Can we try and get those back next week?

May have some additional questions and need for a followup call after that.

Thanks, Tony


3



From: Stieber, Joan (CMS/OL) Sent: Tuesday, November 09,201012:37 PM To: Jacques, Louis B. (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: RE: Further questions on Provenge

Thanks Louis! Are you amenable/available for a call sometime on Friday?

From: Jacques, Louis B. (CMSjOCSQ) Sent: Tuesday, November 09, 2010 12:30 PM To: Stieber, Joan (CMSjOL) Cc: Syrek Jensen, Tamara S. (CMSjOCSQ); Rollins, James (CMSjOCSQ); Leung, Isabella (CMSjOL); Clapton, Erin M. (CMSjOL); Fitterman, Leslye (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Re: Further Questions on Provenge


2, Provenge represents a new class of therapy.


4. Coverage is by case by case at contractor level. The current appearance of consistency is because contractors are waiting for the NCD and held off noncovering. Dendreon fails to appreciate that opening the NCD pre empted local noncoverage. It is disingenuous Wclaim that current situation reflects late June reality.

5. Advance notice is not required for NCD opening. We have never seen evidence of a cms leak. Dendreon never followed up their claims. We cannot control outside speculation.


From: Stieber, Joan (CMSjOL) Sent: Tuesday, November 09,2010 12:04 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMSjOCSQ); Fitterman, Leslye (CMSjOCSQ); Clapton, Erin M. (CMSjOL); Leung, Isabella (CMS/OL); Martino, Maria (CMSjOL) Subject: Further Questions on Provenge



(1) eMS has never before reviewed an oncology product this quickly after FDA approval, before any problems were demonstrated.

1






In addition, Tony notes (for our inform'ation)a general strategy of trying to blur lines between CMS and FDA, suggesting that CMS is really re-opening the FDA's IIsafe and effective" determination.

Tony would appreciate a further conference call with Louis et al. to discuss these questions. I checked Louis' and Tamara's on-line calendars and it looks like you're both out today and tomorrow but that Friday this week (11/12) might work, is that correct? If so, is there a time that would be most convenient for you?

Also, in the interim, if you have any quick responses to the questions above, please feel free to send them to methanks!

-- Joan

From: Stieber, Joan (CMS/OL) [mailto:[email protected]] sent: Friday, November 05, 2010 4:49 PM To: Clapsis, Tony (Finance-Oem) Cc: Oawe, Chris (Finance-Oem); Clapton, Erin M. (CMS/OL) Subject: Re: Provenge ...


We checked with Dr. Louis Jacques, Director of CMS' Coverage & Analysis Group, and he noted that NCDs are frequently requested due to local coverage variation, which indicates disagreement in the medical community about the scientific evidence. If the contractors all agree on coverage policy, there is generally no need for an NCD.


• Allogeneic Stem Cell Transplant for MDS (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=238&basket=nca:00415N:238:Alloge neic+Hematopoietic+Stem+Cell+Transplantation+%28HSCT%29+for+Myelodysplastic+Syndrome:Cl osed:New:12)

• Blood brain barrier disruption chemotherapy (http://www.cms.gov!mcd!viewnca.asp?where=index&nca id=188&basket=nca:00333N:188:Blood+ : Brain+Barrier+Disruption+%28BBBD%29+Chemotherapy:Closed:New:13)

• Microvolt T wave alternans (http://www.cms.gov!mcd/Viewtrackingsheet.asp?id=213)

2


• Nesiritide for Heart Failure (in this case, coverage varied even within a single city because hospitals could nominate their own FI contractor) (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=163&basket=nca:00289N:163:Nesiri tide+for+Treatment+of+Heart+Failure+Patients:Closed:New:24)



-- Joan


From: Clapsis, Tony (Finance-Oem) [mailto:[email protected]] Sent: Thursday, October 28, 2018 11:38 AM To: Clapton, Erin M. (CMS/OL) Cc: Oawe, Chris, (Finance-Oem) Subject: Provenge ...

Hey Erin,


I believe it was examples of where there may have been conflicts In local ~overage decisions, which we talked about as one of the key reasons behind the NCA. Can we try and get those back next week?


Thanks, Tony


3



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 09,201012:44 PM To: Stieber, Joan (CMS/OL) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Re: Further Questions on Provenge

Friday yes Sent from my Blackberry

From: Stieber, Joan (CMS/OL) 1 1

.

Sent: Tuesday, November 09, 2010 12:37 PM To: Jacques, Louis B. (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: RE: Further Questions on Provenge

Thanks Louis! Are you amenable/available for a call sometime on Friday?

From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 09, 2010 12:30 PM To: Stieber, Joan (CMS/OL) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Leung, Isabella (CMS/OL); Clapton, Erin M. (CMS/OL); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Re: Further Questions on Provenge



3. False. See NCO for abarelix.

4. Coverage is by case by case at contractor level. The current appearance of consistency is because contractors are waiting for the NCO and held off noncovering. Dendreon fails to appreciate that opening the NCO pre empted local noncoverage. It is disingenuous to claim that current situation reflects late June reality.

5. Advance notice is not required for NCO opening. We have never seen evidence of a cms leak. Dendreon never followed up their claims. We cannot control outside speculation.


From: Stieber, Joan (CMS/OL) Sent: Tuesday, November 09, 2010 12:04 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMSjOCSQ); Clapton, Erin M. (CMS/OL); Leung, Isabella (CMS/OL); Martino, Maria (CMS/OL) Subject: Further Questions on Provenge

Good morning. I just had a chat with Tony Clapsis (Senate Finance Democratic staff) about arguments being raised on the Hill by the Provenge manufacturer (Dendreon) and advocates, which the Committee staff would like our help in

1


responding to. Tony predicts this issue is only going to get hotter and more politicized, and they want to be able to help

put it in better perspective.

Here are 5 arguments being made about why eMS' actions are inappropriate (with perhaps an underlying implication

that we are therefore motivated by cost?):

(1) CMS has never before reviewed an oncology product this quickly after FDA approval, before any problems were

demonstrated.





In addition, Tony notes (for our information) a general strategy of trying to blur lines between eMS and FDA, suggesting that eMS is really re-opening the FDA's "safe and effective" determination.

Tony would appreciate a further conference call with Louis et a!. to discuss these questions. I checked Louis' and Tamara's on-line calendars and it looks like you're both out today and tomorrow but that Friday this week (11/12) might work, is that correct? If so, is there a time that would be most convenient for you?

Also, in the interim, if you have any quick responses to the questions above, please feel free to send them to me thanksl

-- Joan

From: Stieber, Joan (CMSjOL) [mailto:[email protected]] Sent: Friday, November 05, .2010 4:49 PM To: Clapsis, Tony (Finance-Oem) Cc: Oawe, Chris (Finance-Oem); Clapton, Erin M. (CMSjOL) Subject: Re: Provenge ...

Hi Tony. You had asked for some examples of other NCDs (besides Provenge) that were initiated because of differences across contractors. Please forgive our delay in getting back.to you.

We checked with Dr. Louis Jacques, Director of CMS' Coverage &Analysis Group, and he noted that NCDs are frequently requested due to local coverage variation, which indicates disagreement in the medical community about the scientific evidence. If the contractors all agree on coverage policy, there is generally no need for an NCD.

Here are a few examples where local variability was prominent, along with links to information on the CMS Coverage webpage (some of these were based on external requestsj others were initiated by CMS):

• Allogeneic Stem Cell Transplant for MDS (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=238&basket=nca:00415N:238:Alloge

2


neic+Hematopoietic+Stem+Cell+Transplantation+%28HSCT%29+for+Myelodysplastic+Syndrome:CI osed:New:12)

• Blood brain barrier disruption chemotherapy (http://www.cms.gov/mcd/viewnca.asp?where=index&nca id=188&basket=nca:00333N:188:Blood+ Brain+Barrier+Oisruption+%28BBBO%29+Chemotherapy:Closed:New:13)


• Nesiritide for Heart Failure (in this case, coverage varied even within a single city because hospitals could nominate their ownFI contractor) (http://www.cms.gov/mcd/viewnca.asp?where-index&nca id=163&basket=nca:00289N:163:Nesiri tide+for+Treatment+of+Heart+Failure+Patients:Closed:New:24)



-- Joan


From: Clapsis, Tony (Finance-Oem) [mailto:[email protected]] Sent: Thursday, October 28, 2010 11:38 AM To: Clapton, Erin M. (CMS/OL) Cc: Oawe, Chris (Finance-Oem) Subject: Provenge ...

Hey Erin,


I believe it was examples of where there may have been conflicts In local coverage decisions, . which we talked about as one of the key reasons behind the NCA. Can we try and get those back· next week?


Thanks, Tony


3



From: Graves, Patricia A. (CMS/OCSQ) Sent: Tuesday, November 09, 20102:45 PM To: Ellis, Maria A. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ) Cc: Atkinson, Michelle L. (CMS/OCSQ) Subject: FW: Provenge MEDCAC

Maria,

Please touch base with Security.

Thanks.

Pat

From: Syrek Jensen, Tamara S. (CMSjOCSQ) Sent: Tuesday, November 09, 2010 2:43 PM To: Graves, Patricia A. (CMSjOCSQ); Jacques, Louis B. (CMSjOCSQ) Subject: Re: Provenge MEDCAC

Can't hurt

Sent from BlackBerry

From: Graves, Patricia A. (CMSjOCSQ) Sent: Tuesday, November 09, 2010 02:33 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Subject: Provenge MEDCAC

Should we give security a heads up about the controversial nature ofthe MEDCAC?

1



From: Sent: To:


Fitterman, Leslye (CMS/OCSQ) Friday, November 12, 2010 8:31 AM PASERCHIA, LORI A. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Letter re PROVENGE NEJM91009982.pdf

1



From: [email protected] on behalf of [email protected] Sent: Friday, November 12, 2010 8:50 AM To: Rollins, James (CMS/OCSQ) Subject: NYTimes.com: Prescriptions: Prostate Cancer Drug Gets Lukewarm Review

I M ="~--"---,-----"--'~ 1M , ,."...--'----" ----.---~ ~ I This page was sent to you by: [email protected]

REALTH INovember 10, 2010

Prescriptions: Prostate Cancer Drug Gets Lukewarm Review By ANDREW POLLACK .

The analysis was issued as Medicare decides whether to pay for an expensive drug, Provenge.

Copyright 2010 The New York Times Company I Privacy Policy

~

1


(b)(5) - Predecisional(b)(5) -PPPredecisional


(b)(5) - Predecisional(b)(5) -PPPredecisional



From: Jacques, Louis B. (CMS/OCSQ) Sent: Saturday, November 13, 2010 7:33 PM To: Hall, Amy (CMS/OL); Ashkenaz, Peter (CMS/OEABS) Cc: Clapton, Erin M. (CMS/OL); Stieber, Joan (CMS/OL); Syrek Jensen, Tamara S. (CMS/OCSQ);

Rollins, James (CMS/OCSQ) Subject: Re: Washington Post article: Review of prostate cancer drug Provenge renews medical cost

benefit debate

The ones I sent Friday morning are the latest version. Sent from my Blackberry

From: Hall, Amy (CMS/OL) Sent: Saturday, November 13, 2010 04:27 PM To: Ashkenaz, Peter (CMS/OEABS) Cc: Clapton, Erin M. (CMS/OL); Stieber, Joan (CMS/OL); Jacques, Louis B. (CMS/OCSQ) Subject: Re: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

Could you fwd it to me and I can try to make it into an answer for a potential Q .....

From: Ashkenaz, Peter (CMS/OEABS) Sent: Saturday, November 13, 2010 04:26 PM To: Hall, Amy (CMS/OL) Cc: Clapton, Erin M. (CMS/OL); Stieber, Joan (CMS/OL); Jacques, Louis B. (CMS/OCSQ) Subject: Re: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

Louie has ger:leral TPs, I have the letter to the editor that never got cleared.

Please forgive any errors, this was sent using BlackBerry

From: Hall, Amy (CMS/OL) Sent: Saturday, November 13, 2010 02:04 PM To: Ashkenaz, Peter (CMS/OEABS) Cc: Clapton, Erin M. (CMS/OL); Stieber, Joan (CMS/OL); Jacques, Louis B. (CMS/OCSQ) Subject: FW: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

Did you ever have TPs on why this article was just plain wrong? Would be useful to give to Don for prep. We expect this issue, and the Post article in particular[ to come up at his hearing.

From: Jacques,' Louis B. (CMS/OCSQ) Sent: Monday, November 08, 2010 12:16 PM To: Stieber, Joan (CMS/OL); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Schafer, Jyme H. (CMS/OCSQ); Griffith, Ellen B. (CMS/OEA); Ashkenaz, Peter (CMS/OEABS); Hall, Amy (CMS/OL); Clapton, Erin M. (CMS/OL); Burney, Ira (CMS/OL); Martino, Maria (CMS/OL); Hunt, Rebecca J. (CMS/OL); Leung, Isabella (CMS/OL) Subject: Re: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

Joan

Already disc with Peter A. The article is just plain wrong.

Louis

1



From: Stieber, Joan (CMSjOL) Sent: Monday, November 08,2010 12:11 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ); Rollins, James (CMSjOCSQ); Schafer, Jyme H. (CMSjOCSQ); Griffith, Ellen B. (CMSjOEA); Ashkenaz, Peter (CMSjOEABS); Hall, Amy (CMSjOL); Clapton, Erin M. (CMSjOL); Burney, Ira (CMSjOL); Martino, Maria (CMSjOL); Hunt, Rebecca J. (CMSjOL); Leung, Isabella (CMSjOL) Subject: Washington Post article: Review of prostate cancer drug Provenge renews medical cost-benefit debate

In case you haven't seen this already, there's a front page article in today's Washington Post about the Provenge coverage analysis (pasted in below FYI). I am particularly disturbed by the first sentence's assertion that this is "an unusual review". In fact, as we (and Louis) have recently explained to several Congressional inquirers, initiation of an NCO review in cases of contractor variation is quite routine. The 7th paragraph also seems carelessly drafted in saying: "Because men tend to be elderly when they get diagnoses of advanced prostate cancer, Medicare's decision will have a major effect on Provenge's availability. Regional Medicare providers paying for Provenge would have to stop. Private insurers also tend to follow Medicare's lead." - seeming to suggest that a non-coverage decision is expected. The article focuses almost entirely on cost as opposed to effectiveness questions, and suggests a differential racial impact.


tha nks - Joan in OL

Review of prostate cancer drug Provenge renews medical cost-benefit debate By Rob Stein Washington Post Staff Writer Monday, November 8, 2010; 7:52

Federal officials are conducting to determine whether the government should pay for an expensive new vaccine for treating prostate cancer, rekindling debate over whether some therapies are too costly. The Centers for Medicare & Medicaid Services, which dictate what treatments the massive federal healthinsurance program for the elderly will cover, is running a "national coverage analysis" of Provenge, the first vaccine approved for treating any cancer. The treatment costs $93,000 a patient and has been shown to extend 'j .

patients' lives by about four months. Although Medicare is not supposed to take cost into considerati6n when making such rulings, the decision to launch a formal examination has raised concerns among cancer experts, drug companies, lawmakers, prostate cancer patients and advocacy groups. Provenge, which was approved for advanced prostate cancer in April, is the latest in a series ofnew high-priced , cancer treatments that appear to eke out only a few more months of life, prompting alarm about their cost. . "This absolutely is the opening salvo in the drive tosave money in the health-care system," saidSkip Lockwood, who heads Zero ~ the Project to End Prostate Cancer, a Washington-based lobbying group. "If the cost wasn't a consideration, this wouldn't even be under discussion." Those concerns have been heightened because the review comes after the bitter health-care reform debate, which was marked by accusations about rationing and "death panels." The appointment ofDonald M. Berwick to head Medicare only intensified anxieties. President Obama sidestepped a Senate battle by naming Berwick, who has advocated for scrutinizing costs, when Congress was in recess in July. Because men tend to be elderly when they get dia noses of advanced rostate cancer, Medicare's decision will have a major effect on Provenge's availability.


2


,"

Medicare officials, who are convening a panel of outside advisers to vet the issue at a public hearing Nov. 17, say Provenge's price tag isn't an issue. But Berwick and other officials declined to discuss the rationale for the reVIew. "Certainly no one in the Medicare program would publicly state that the price tag would have anything to do with Medicare looking at it. But they are human beings, too. They notice things like that," said Sean Tunis, director of the Center for Medical Technology Policy and a former chief medical officer at Medicare. Tunis said, though, that other factors, such as the special nature of the therapy and lingering questions about its effectiveness, were probably playing a more crucial role. The review comes as the Food and Drug Administration considers withdrawing an approval for another expensive cancer treatment- A vastin for metastatic breast cancer - which triggered a similar debate even though the FDA too is not supposed to factor costs into its analyses. Medicare usually covers new cancer drugs once they have been approved by the FDA. The decision in June to scrutinize Provenge prompted several members of Congress to question the action. Supporters have inundated the agency with hundreds of thousands of comments. "I don't want to blame Obamacare, but it just kind of figures that people are taking a look at what the costbenefit ratios are and all that sort of stuff," said David Dykes, 69, of Lorton, a retired federal employee who was hoping to try Provenge. "That may sound pretty good to the people who want to cut costs, but it doesn't sound too good to me. This is something that could extend my life. I'd like to give that a shot." Some fear the move will discourage pharmaceutical companies from developing new cancer drugs. "It is extremely chilling if, after spending a huge sum of money, time and effort to get a drug through FDA approval, you'll then have to go tlu:ough it all again to see if CMS will pay for it," said Allen S. Lichter, head of the American Society of Clinical Oncology. "Firing a shot across the bow like this is not the way to have an intelligent and meaningful discussion about how we start to address the complex issue of drug costs." Provenge has long been the center of controversy. The FDA delayed Provenge's approval in 2007. The rejection triggered outrage among patients, advocates and investors in Dendreon, the Seattle company that deVeloped Provenge. The campaign to win Provenge's approval included anonymous death threats, accusations ofconflicts of interest, protests, congressional lobbying and vitriolic Internet postings. Prostate cancer strikes 192,000 men in the United States each year and kills about 27,000. The only therapies are surgery, radiation, hormones and the chemotherapy drug Taxotere. Unlike standard vaccines, which are given before someone gets sick to stimulate their immune system to fight off infections, Provenge is a "therapeutic vaccine," designed to attack cancer cells in the body. To produce Provenge, doctors remove immune system cells from patients, expose the cells in the laboratory to a , protein found on most prostate cancer cells and an immune system stimulator, and infuse the cells back into the ' patient in a month-long series of three treatments. In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months. "To charge $90,000 for four months, which comes out to $270,00 for a year of life, I think that's too expensive," , said Tito Fojo of the National Cancer Institute. "A lot of people will say, 'It's my $100,000, and it's my four months.' Absolutely: A day is worth $1 million to some people. Unfortunately, we can't afford it as a society." Others agreed, especially given the modest benefit. . "I'd like to think cost doesn't need to come up when it's a slam dunk," said H. Gilbert Welch of the Dartmouth Institute for Health Policy ,and Clinical Practice. "But when it's a close call like this, it certainly has to be a factor. That's $100,000 Medicare can't spend elsewhere." But~l}~e cRn;II1;~nt~rYe~s caused wides read alarm amongpatients and advocates. "f~~.~ll;l.ii{[;' 'IfCMS doesn't approve this, then this treatment becomes an exclusive kind of treatment for men who can afford it out of pocket," said Thomas Farrington, president of the Prostate Health Education Network. Others stressed that many men live far longer on the treatment and that even four months is extremely valuable to some. "Whenever you are faced with a disease where you can lose your life, you really would like to extend it as much as you can," said Leibel B. Harelik, 61, a prostate cancer patient who is executive director of the Prostate Cancer Resource Center in Austin.

3


· Company officials say the cost is not out of line with that of other cancer drugs. Each treatment with Provenge, which the company estimates cost nearly $1 billion to develop, is tailored to each patient. "Because of that, we have higher costs associated with this product," said Mitchell H. Gold, Dendreon's chief executive. "Provenge is a upique new medicine that prolongs the lives of patients with late-stage prostate cancer. These patients need access to innovative new medicines." Whatever the outcome on Provenge, many on both sides agreed that more debate over other new high-tech therapies was likely to come. "At some point, if we keep paying these very high prices for treatments that provide very limited benefit, we're going to reach the point where we can no longer afford health care," said Alan Garber, a professor ofmedicine and economist at Stanford University. "Some say we're living through that right now."

4



From: Jacques, Louis S. (CMS/OCSQ) Sent: Monday, November 15, 2010 4:00 PM

I To: Wilson, Laurence D. (CMS/CMM); Kelman, Jeffrey A. (CMS/CM); Warren, John F. (CMS/CMM); Sassano, Amy (CMS/CMM)

C~: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: Re: Provenge

Every NCD includes a formal bcd Sentfrom my Blackberry

From: Wilson, Laurence D.,{CMS/CMM) Sent: Monday, November 15, 2010 03:.52 PM To: Kelman, Jeffrey A. (CMS/CM); Warren, John F. (CMS/CMM); Jacques, Louis S. (CMS/OCSQ); Sassano, Amy (CMS/CMM) Subject: RE: Provenge

FYI-I understand from Cindy Hake that this is on the agenda as a simple status update-the workgroup knows an NCD is pending so no decision/recommendation by the workgroup on coding will be made at this point. So no reason for

. anyone to be concerned .... just a routine business item.

Laurence D. Wilson Director

,i \.

Chronic Care Policy Group Center for Medicare Management Centers for Medicare & Medicaid Services

(410) 786-4603

CONFIDENTIALITY NOTICE: This e-mail message, including any attachments, is for the sole use of the intended recipient(s) and may contain confidential and privileged information or otherwise protected by law. Any unauthorized review, use., disclosure or distribution is prohibited. If you are not the intended reCipient, Jl~~~~_..92D_~_~U!2.~~,~~~~_b,tEf:)PIy~::.!!!,~i:I~_~U!~.s.t~oy 3,l1!,.9'!pif:)~~!~~22Q_iD~.f:)~~~~f:): __., __.__ ,_.. _._. __._ ....•_~_____,__.__.._._._... __.._•. ~.... "

IFrom: Kelman, Jeffrey A. (CMS/CM) Sent: Monday, November 15, 2010 1:18 PM To: Warren, John F. (CMS/CMM); Wilson, Laurence D. (CMS/CMM); Jacques, Louis S. (CMS/OCSQ); Sassano, Amy (CMS/CMM) Subject: Re: Provenge

This is sensitive enough that I would follow standard processes. It will become political very quickly This is immunotherapy with autologous white cell transdusion, not exactly a Vaccine or drug.

Sent from my BlackBerry Wireless Device

From: Warren, John F. (CMS/CMM) Sent: Monday, November 15, 2010 12:41 PM To: Wilson, Laurence D. (CMS/CMM); Jacques, Louis S. (CMS/OCSQ); Kelman, Jeffrey A. (CMS/CM); Sassano, Amy (CMS/CMM) Subject: RE: Provenge

1

/ /'






· "


From: Stieber, Joan (CMS/OL) Sent: Tuesday, November 16, 2010 4: 15 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Thanks Louis. A few q'uestions:

(1) In your note below, you describe Abarelix as "the best example of both an on label new cancer therapy and local contractor concerns". However the table at the end your attachment says "No" under the heading "Inconsistencies Across Local Contractors". Can you clarify?

I !

(2) In fact, in the table, only 2 of 8 examples say "Yes" for "Inconsistencies Across Local Contractors" (all others say· I either "No" or "Information unavailable"). Yet you note that "NCDs inherently occur in a context of local coverage

I I variation". I assume this statement takes precedence over the chart??

(3) I assume the other (non-cancer) examples mentioned in your note below are intended as additional examples, apart from the cancer examples addressed in the attachment - is that correct?

thanks - Joan

p.s. I'm coming to the MEDCAC meeting tomorrow and look forward to seeing you there.

From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 16, 2010 10:30 AM To: Stieber, Joan (CMS/OL); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ); Rollins,James (CMS/OCSQ) . Subject: RE: Follow up to Senate Finance Call on Provenge

Joan,

Attached is the summary text and table. As background, NCDs inherently occur in a cdntext of local coverage variation with small exceptions, e.g. when contractor denials are being overturned by AUs - since AUs must defer to NCDs. Sometimes this variation is explicitly cited as a reason for opening, more often it's just background awareness.

Noncancer examples include on label use of the heart drug Nesiritide for heart failure, where hospitals in the same city would have diff~rent Medicare Fls and thus different coverage. Contractors also differed on Anodyne infrared therapy for neuropathy, with ,the DM ERCs noncovering but some other carriers covering in the office setting.

Bone Marrow Transplant is a HRSA regulated activity. Provides an example of CMS opening an NCD on a topic relevant to another HHS agency because of local contractor variation.

NB. Though there is dome debate as to whether MDS (myelodysplastic syndrome) is a cancer or a precursor to cancel', the NCllists it as a cancer. Here's the link http://www.cancer.gov/cancertopics/types/myeloproliferative

1


· Abarelix is the best example of both an on label new cancer therapy and local contractor concerns. The Zevalin/Bexxar is an example of a novel therapy - though that NCO eventually closed with a decision to leave it at local contractor discretion. Blood Brain barrier also highlights local coverage differences.

Louis

From: Stieber, Joan (CMS/OL) Sent: Monday, November 15, 2010 6:08 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: Follow up to Senate Finance Call on Provenge

Hi Louis. A belated thank you for your help with the call for Tony Clapsis (Senate Finance majority) last Friday. According to my notes, he asked for 3 follow-up items in writing:

(1) Examples of other cancer drugs for which we've done NCDs (particularly for on-label uses) (2) Examples of NCDs opened to address inconsistencies across contractors (3) Examples of NCDs focused on a new product/novel technology (we noted that most such examples involve devicesJ

not drugs - that's OK)

I think he wants these in written form so he can circulate to his colleagues, ideally prior to the SFC hearing w/ Dr. Berwick on Wednesday morning.

Is that something you or your staff could whip up e¥peditiously?

thanks very much -Joan in OL

2



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 16, 20104:34 PM To: Stieber, Joan (CMS/OL); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ);.PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ); ROllins,James (CMS/OCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Joan,

Re: Abarelix: see paste from the requestor letter below.

By granting coverage through an NCD, CMS will speed the uptake of this very important therapy to patients who may otherwise be deprived of its use if the more time- and . of from each of the individual Medicare carriers and fiscal intermediaries.

As I mentioned in the earlier email, we have no need to explicitly mention local inconsistency in every NCD,even when it is in the background.

The others examples in my note were additional noncancer FYls.

Louis

From: Stieber, Joan (CMSjOL) Sent: Tuesday, November 16, 20104:15 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Fitterman, Leslye (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Thanks Louis. A few questions:


(2) In fact, in the table, only 2 of 8 examples say "Yes" for "Inconsistencies Across Local Contractors" (all others say either "No" or "Information unavailable"). Yet you note that "NCDs inherently occur in a context of local coverage variation". I assume this statement takes precedence over the chart ??

(3) I assume the other (non-cancer) examples mentioned in your note below are intended as additional examples, apart from the cancer examples addressed in the attachment - is that correct?

thanks - Joan


1


.. .' .~~. "., '. ",. .

From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 16, 2010 10:30 AM To: Stieber, Joan (CMS/OL)i Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ)i PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)i Ashby, Lori M .. (CMS/OCSQ)i Rollins, James (CMS/OCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Joan,

Attached is the summary text and table. As background, NCDsinherently occur ina context of local coverage variation with small exceptions, e.g. when contractor denials are being overturned by AUs .,-since AUs must defer to NCDs. Sometimes this variCition is explicitly cited as a reason for opening, more often it's just background awareness.

Noncancer examples include on label use of the heart drug Nesiritide for heart failure, where hospitals in the same city would have different Medicare Fls and thus different coverage. Contractors also differed on Anodyne infrared therapy for neuropathy, with the DMERCs noncovering but some other carriers covering in the office setting.

Bone Marrow Transplant is a HRSA regulated activity. Provides an example of CMS opening an NCO on a topic relevant to another HHS agency because of local contractor variation.

NB. Though there is dome debate as to whether MDS (myelodysplastic syndrome) is a cancer or a precursor to cancer, the NCllists it as a cancer. Here's the link http://www.cancer.gov/cancertopics/types/myeloproliferative

Abarelix is the best example of both an on label new cancer therapy and local contractor concerns. The Zevalin/Bexxar is an example of a novel therapy - though that NCD eventually closed with a decision to leave it at local contractor discretion. Blood Brain barrier also highlights local coverage differences.

Louis

From: Stieber, Joan (CMS/OL) Sent: Monday, November 15, 2010 6:08 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: Follow up to Senate Finance Call on Provenge .

Hi Louis. A belated thank you for your help with the call for Tony Clapsis (Senate Finance majority) last Friday. According to my notes, he asked for 3 follow-up items in writing: .

(1) Examples of other cancer drugs for which we've done NCDs (particularly for on-label uses) (2) Examples of NCDs opened to address inconsistencies across contractors . (3) Examples of NCDsfocused on a new product/novel technology (we noted that most such examples involve devices, not drugs - that's OK)

I think he wants these in written form so he can circulate to his colleagues, ideally prior to the SFC hearingw/ Dr. Berwick on Wednesday morning.

Is that something you or your staff could whip up expeditiously?

thanks very much - Joan in OL

2



From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, November 16,20104:37 PM To: Stieber, Joan (CMS/OL); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Joan,

More from the Abarelix requestor letter

Coverage by an NCD will also help to alleviate concerns that the risk management program.agreed upon by Praecis with the FDA will be disregarded by providers and that uncontrolled,offlabel use ofPlenaxis™ will result. By clarifying coverage and non-coverage as suggested in this request, off label use not conforming to the risk management plan can be checked. Without an NCD, uneven, inconsistent and inappropriate coverage is almost certain to occur.

From: Stieber, Joan (CMSjOL) Sent: Tuesday, November 16, 2010 4: 15 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Fitterman, Leslye (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

Thanks Louis. A few questions:


(2) In fact, in the table, only 2 of 8 examples say "Yes" for "Inconsistencies Across Local Contractors" (all others say either "No" or "Information unavailable"). Yet you note that "NCDs inherently occur in a context of local coverage variation". I assume this statement takes precedence over the chart ??

(3) I assume the other (non-cancer) examples mentioned in your note below are intended as additional examples, a'part from the cancer examples addressed in the attachment - is that correct?

thanks - Joan


From: Jacques, Louis B. (CMSjOCSQ) Sent: Tuesday, November 16, 2010 10:30 AM To: Stieber, Joan (CMSjOL); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Fitterman, Leslye (CMSjOCSQ); PASERCHIA, LORI A. (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Ashby, Lori M. (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: RE: Follow up to Senate Finance Call on Provenge

1

i I


'; ," ,~,,---- .

Joan,

Attached is the summary text and table. As background, NCDs inherently occur in a context of local coverage variation with small exceptions, e.g. when contractor denials are being overturned byAUs - sinceAUs must defer to NCDs. Sometimes this variation is explicitly cited as a reason for opening, more often it's just background awareness.

Noncancer examples include on label use of the heart drug Nesiritide for heart failure, where hospitals inthe same city would have different Medicare Fls and thus different coverage. Contractors also differed on Anodyne infrared therapy for neuropathy, with the DMERCs noncovering but some other carriers covering in the office setting.

Bone Marrow Transplant is a HRSA regulated activity. Provides an example of CMS opening an NCD on a topic relevant to another HHS agency because of local contractor variation.

NB. Though there is dome debate as to whether MDS (myelodysplastic syndrome) is a cancer or a precursor to cancer, the NCllists it as a cancer. Here's the link http://www.cancer.gov!cancertopics/types!myeloproliferative

Abarelix is the best example of both an on label new cancer therapy and local contractor concerns. The Zevalin/Bexxar is an example of a novel therapy - though that NCD eventually closed with a decision to leave it at local contractor discretion. Blood Brain barrier also highlights local coverage differences.

Louis

From: Stieber, Joal) (CMSjOL) Sent: Monday, November 15, 2010 6:08 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMSjOCSQ) Subject: Follow up to Senate Finance Call on Provenge

Hi Louis. A belated thank you for your help with the call for Tony Clapsis (Senate Finance majority) last Friday. According to my notes, he asked for 3 follow-up items in writing:

(1) Examples of other cancer drugs for which we've done NCDs (particularly for on-label uses) (2) Examples of NCDs opened to address inconsistencies across contractors (3) Examples of NCDs focused on a new product/novel technology (we noted that most such examples involve devices, not drugs - that's OK)

I think he wants these in written form so he can circulate to his colleagues, ideally prior to the SFC hearing wi Dr. Berwick on Wednesday morning.

Is that something you or your staff could whip up expeditiously?

thanks very much -Joan in OL

2



From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Wednesday, November 17, 2010 3:50 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); DOlina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ);

Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Guchemand, John (CMS/OCSQ)

Subject: Score sheet for the MEDCAC Nov 17 Attachments: November 17th MEDCAC Scoresheet with Scores.xls

Maria and I have compared the results to the worksheets the panel members filled out. Please take a look and let me know if you would like me to make any changes.

Thanks Michelle


1


· I


From: Syrek Jensen, Tamara S. (CMS/OCSQ) Sent: Wednesday, November 17, 20104:54 PM To: Jacques, Louis B. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ)Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ);

Ellis, Maria A (CMS/OCSQ); Graves, Patricia A (CMS/OCSQ); Guchemand, John (CMS/OCSQ)

Subject: RE: Score sheet for the MEDCAC Nov 17

I can't approve because my password does not work anymore. Elaine will post first thing in the morning.

Tamara Syrek Jensen Deputy Director Coverage and Analysis Group Office of Clinical Standards and Quality, CMS 7500 Security Blvd. Baltimore( MD 21244 (410) 786-3529 . [email protected]

From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday( November 17, 2010 4: 15 PM To: Atkinson, Michelle L. (CMS/OCSQ); Syrek Jensen( Tamara S. (CMS/OCSQ) Cc: Rollins( James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Guchemand( John (CMS/OCSQ) Subject: Re: Score sheet for the MEDCAC Nov 17

looks good. Ok to post. Sent from my Blackberry

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Wednesday, November 17( 2010 03:49 PM To: Jacques( Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins( James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Guchemand( John (CMS/OCSQ) Subject: Score sheet for the MEDCAC Nov 17

Maria and I have compared the results to the worksheets the panel members filled out. Please take a look

\

and let me know if you would like me to make any changes.

Thanks Michelle


1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday, November 17, 20104:15 PM To: Atkinson, Michelle L. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ);


Subject: Re: Score sheet for the MEDCAC Nov 17

Looks good. Ok to post. Sent from my Blackberry

From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Wednesday, November 17, 2010 03:49 PM To: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Guchemand, John (CMS/OCSQ) Subject: Score sheet for the MEDCAC Nov 17


Thanks Michelle


. i,

1



From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday, November 17, 20104:58 PM To: Syrek Jensen, Tamara S.(CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ);


Subject: Re: Score sheet for the MEDCAC Nov 17

Ok Sent from my Blackberry

From: Syrek Jensen, Tamara S. (CMSjOCSQ) Sent: Wednesday, November 17, 201004:53 PM To: Jacques, Louis B. (CMSjOCSQ); Atkinson, Michelle L. (CMSjOCSQ) Cc: Rollins, James (CMSjOCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMS/OCSQ); Guchemand, John (CMS/OCSQ) Subject: RE: Score sheet for the MEDCAC Nov 17

I can't approve because my password does not work anymore. Elaine will post first thing in the morning.

Tamara Syrek Jensen Deputy Director Coverage and Analysis Group Office of Clinical Standards and Quality, CMS 7500 Security Blvd. Baltimore, MD 21244 (410) 786-3529 [email protected]

. From: Jacques, Louis B. (CMSjOCSQ) Sent: Wednesday, November 17,20104:15 PM To: Atkinson, Michelle L. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMSjOCSQ); Graves, Patricia A. (CMS/OCSQ);Guchemand, John (CMS/OCSQ) Subject: Re: Score sheet for the MEDCAC Nov 17


From: Atkinson, Michelle L. (CMS/OCSQ) Sent: Wednesday, November 17, 2010 03:49 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Dolina, Elaine L. (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ); Graves, Patricia A. (CMSjOCSQ); Guchemand, John (CMS/OCSQ) Subject: Score sheet for the MEDCAC Nov 17


1


Thanks Michelle


2

:, I

(


" -~---",:


From: Dolina, Elaine L. (CMS/OCSQ) Sent: Thursday, November 18, 2010 7:44 AM To: Jacques, Louis B. (CMS/OCSQ); Atkinson, Michelle L. (CMS/OCSQ); Syrek Jensen, Tamara

S. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Manlove, John (CMS/OCSQ); Ellis, Maria A. (CMS/OCSQ);

Graves, Patricia A. (CMS/OCSQ); Guchemand, John (CMS/OCSQ) Subject: RE: Score sheet for the MEDCAC Nov 17

Posted!

http://www.cms.gov/mcd/viewmcac.asp?where=index&mid-56

,

From: Jacques, Louis B. (CMSjOCSQ) Sent: Wednesday, November 17, 2010 4:15 PM To: Atkinson, Michelle L. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Rollins, James (CMSjOCSQ); Dolina, Elaine L. (CMSjOCSQ); Manlove, John (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ); Guchemand, John (CMSjOCSQ) Subject: Re: Score sheet for the MEDCAC Nov 17


From: Atkinson, L. (CMSjOCSQ) Sent: Wednesday, November 17, 2010 03:49 PM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: Rollins, James (CMSjOCSQ); Dolina, Elaine L. (CMSjOCSQ); Manlove, John (CMSjOCSQ); Ellis, Maria A. (CMSjOCSQ); Graves, Patricia A. (CMSjOCSQ); Guchemand, John (CMSjOCSQ) Subject: Score sheet for the MEDCAC Nov 17

Maria and I have compared the results to the worksheets the panel memqers filled out. Please take a look and let me know if you would like me to make any

changes.

Thanks Michelle

Michelle Atkinson OCSQ/CAG/DO!M 410-786-2881

J '

'I

I : ) i

1



From: Fitterman, Leslye (CMS/OCSQ) Sent: Thursday, November 18, 2010 8:01AM To: Rollins, James (CMS/OCSQ) Subject: The internal timeline for preparing the DM for Immunotherapy for Prostate Cancer Attachments: INTERNAL TIMELlNE.docx

II :

1


(b)(6)(b)(6)(b)(6)(b)(6)(b)(6)(b)(6)



From: Stiller, Jean M. (CMS/OCSQ) Sent: Thursday, November 18, 20101:03 PM To: Jacques, Louis B. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye

(CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ) Subject: fyi on Provenge.

http://prescriptions.blogs.nyti mes.com/2010/11/17/medica re-pa nel-backs-prostate-d rug/? pa rtner=rss&emc=rss

1



From: Sent: To: Cc: Subject: Attachments:

Jim:

Fitterman, Leslye (CMS/OCSQ) Monday, November 22, 2010 3:01 PM Rollins, James (CMS/OCSQ) Ashby, Lori M. (CMS/OCSQ) Chambliss Isakson Letter re PROVENGE NCA Chambliss & Isakson letter to DB.pdf; Chambliss Isakson response 102210.docx; SUMADMIN Chambliss Isakson .DOC

Attached please find the letter to Dr. Berwick from Senators Chambliss and Isakson, along with the CAG response and summary statement. This response and summary statement uses the same language as the OA used to reply to

Senators Specter and Kerry.

Leslye

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From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, November 22,20104:16 PM To: Fitterman, Leslye (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: Provenge BCD

Have we sent a formal BCD request to CM?

Louis B. Jacques, MD Director, Coverage & Analysis Group Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Mailstop C1-09-06 7500 Security Blvd Baltimore MD 21244 (410) 786-4512 (410) 786-9286 (FAX) [email protected]

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Monday, November 22,20104:18 PM To: Jacques, Louis B. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Provenge BCD

Not that I am aware of. Will do that early in the a.m.

From: Jacques, Louis B. (CMSjOCSQ) Sent: Monday, November 22, 2010 4: 16 PM To: Fitterman, Leslye (CMSjOCSQ); Pencek, Eileen (CMSjOCSQ); Rollins, James (CMSjOCSQ) Subject: Provenge BCD


Louis B. Jacques, MD Director, Coverage & Analysis Group Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Mailstop C 1-09-06 7500 Security Blvd Baltimore MD 21244 (410) 786-4512 (410) 786-9286 (FAX) [email protected]

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, November 23,20107:11 AM To: Jacques, Louis B. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: RE: Provenge BCD

We submitted a formal request on June 29, 2010.

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, November 22,2010 4:16 PM To: Fitterman, Leslye,(CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Rollins, James (CMS/OCSQ) Subject: Provenge BCD


Louis B. Jacques, MD Director, Coverage & Analysis Group Office of Clinical Standards and Quality Centers for Medicare & Medicaid Services Mailstop C1-09-06 7500 Security Blvd Baltimore MD 21244 (410) 786-4512 (410) 786-9286 (FAX) [email protected]

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, November 23,20108:47 AM To: Ashby, Lori M. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ) Subject: Chambliss Isakson response 102210 (2).docx Attachments: Chambliss Isakson response 102210 (2).docx

One change pointed out by Louis.

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, November 24,20101 :19 PM To: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.(CMS/OCSQ) Subject: FW: [Health Affairs Blog] Thoughtful Purchasing AtCMS

FYI

From: Anderson, Kelly (CMSjOCSQ) Sent: Wednesday, November 24, 2010 11:54 AM To: Fitterman, Leslye (CMSjOCSQ) Subject: FW: [Health Affairs Blog] Thoughtful Purchasing At CMS

If you haven't already seen ....

From: Health Affairs [[email protected]] Sent: Wednesday, November 24, 2010 9:21 AM To: [email protected] Subject: [Health Affairs Blog] Thoughtful Purchasing At CMS

Health Affairs Blog has posted a new item, 'Thoughtful Purchasing At CMS' by Dan Mendelson

Recent press reports on Medicare's decision to evaluate coverage policy for the new cancer therapy Provenge were highly critical of the Centers for Medicare and Medicaid Services (CMS) and its role in examining the evidence behind FDAapproved products. Let's take a step back. In fact, this is exactly what CMS should be doing - carefully considering the evidence to make a determination on whether a new therapy is reasonable and necessary and thus appropriate for payment by the Medicare program. Subverting this function is in no one's best interest. As Provenge is a novel approach for treating advanced prostate cancer, clinical testing focused on late stage patients. The Medicare Coverage Advisory Committee (MEDCAC) members expressed general confidence that the current body of evidence supports coverage of the on-label use of Provenge, but emphasized that gaps still exist in evaluating the product's performance in the Medicare population. Further, the panel indicated that more evidence is needed to determine Provenge's safety and effectiveness in off-label indications. The review of Provenge by CMS and its MEDCAC is not unusual. Many National Coverage Decisions (NCDs) made last year -and in years prior - focus on novel technologies, and often in the cancer field. In many cases, Medicare allowed for coverage for a limited population and also required additional data. Avalere's analysis of NCDs shows that from 2008 to 2010, CMS made coverage conditional on the collection of additional data in nearly 25 percent of NCDs. Further, analysis of data from the Avalere EBM Navigator demonstrates that oncology ranks as a top therapeutic area in which the federal government has deployed millions of dollars on comparative effectiveness research. Medicare's focus on oncology will only intensify in the future. Serious evaluation of new technologies is a core activity for any commercial insurance company - it's expected by employers and enrollees. Likewise, the activities of the Coverage and Analysis Group at CMS are a core function for Medicare in its role as a payer. Subverting Medicare's ability to evaluate technologies would inevitably invite payment for technology that shouldn't be used by Medicare benefiCiaries, and could result in lapses in Medicare program integrity. Being a prudent purchaser has been a core strategiC objective of the agency dating back to the early 2000s.

Now a word about the price tag - also a subject of some hysteria in press reports. Despite accounts to the contrary, CMS did not make cost the sole basis for its Provenge decision. Many of the technologies that have been analyzed by the MEDCAC over the past few years, such as implantable cardiac defibrillators, are aSSOCiated with higher Medicare costs. It's counter-productive to vilify an agency for targeting its evidence-review resources on technologies that may be widely used in Medicare and have significant implications to its budget. That's sensible management commonly employed by commercial insurers in the US, not rationing.

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Of course, the growing use of NCDs does have an impact on industry, but one that should be positive in the long run for driving real innovation. The bar is going up for evidence, and CMS - like private insurers- continues to demand more real-world data. Fortunately, the industry is rising to the call to generate more evidence on the safety, efficacy, and effectiveness of its products and to accommodate the demands of payers all across the globe. As these data become available, payers will likewise need to rise to the call of making valuable technologies fully accessible to beneficiaries who may benefit from them.

You may view the latest post at http://healthaffairs.org/blog/2010/11/24/thoughtful-purchasing-at-cmsl

You received this e-mail because you asked to be notified when new updates are posted. Best regards, Health Affairs [email protected]

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From: Ashby, Lori M. (CMS/OCSQ) Sent: Thursday, December 09, 2010 7:45 AM To: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, TamaraS. (CMS/OCSQ) 'Subject: FW: SWIFT Folder sent to DC Attachments: Isakson Draft Language.docx; Chambliss Draft Language.docx; Summary Statement.docx

FYI-this letter on Provenge will be presented to the Administrator for signature at Friday's Issues meeting.

Lori M. Ashby

Special Assistant OCSQlCoverage and Analysis Group 410-786-6322 [email protected]

Notice: The contents of this message and any attachments may be privileged and confidential. Please do not disseminate without the approval of the Centers for Medicare &: l'vledicaid Services. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy, forward, disseminate, or otherwise usc the information. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.

From: Andrews, Danielle Y. (CMS/OCSQ) Sent: Wednesday, December 08,2010 11:26 AM To: Ashby, Lori M. (CMS/OCSQ) Subject: FW: SWIFT Folder sent to DC

For the OCSQ Issues meeting, it's a signature item for CAG

From: Williams, Jackson (CMS/OEORA) Sent: Wednesday, December 08,2010 11:23 AM To: Andrews, Danielle Y. (CMS/OCSQ) Subject: FW: SWIFT Folder sent to DC

Here is our first signature item for Friday. It is another Provenge letter.

I saw that your Thursday time got cancelled because Dr. Berwick has a patient safety meeting at the White House then. Please let me know if you have any materials for that meeting that need to go in Dr. Berwick's book tomorrow.

From: Robinson, Jennifer S. (CMS/OEORA) Sent: Wednesday, December 08, 2010 11:10 AM To: Williams, Jackson (CMS/OEORA) Subject: SWIFT Folder sent to DC

Chambliss - 111720104035

jenniJcr S. RobinsoIl Health InsuraIlcc SpcciaJi~t Officc of SU'atcgic Opcrations and Rc/,'1.I.Iatory Affairs

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Division of CorrespomIellce Ma.nagement CMS 1 U.S. Department of Health & HumallScrviccs 7500 SeCUlity Boulevard 1 Baltimore, Maryland 21244-1850 Phone: 4.I0-786-2066 Mai1.~top: CS-ll-24 Location C5-12-20 Email: [email protected]

Confidentiality Notice: This e-mail message, including any attachments, is for the sole use of the intended recipient(s) and may contain confidential and privileged information. Ifyou are not the intended recipient, or an authorized agent of the intended recipient, please immediately contact the sender by reply e-mail and destroy/delete all copies of the original message. Any unauthorized review, use, copying, forwarding, disclosure, or distribution by other than the intended recipient or authoriied agent is prohibited .,

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, December 10, 2010 10:50 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ) Subject: RE: Provenge

This allows coverage for Provenge under (a)(l)(A)

II. National Coverage Determinations

Under the authority of section 1862(a)(1)(A), the NCD process may result in one of the following coverage decisions:

1. No change in coverage. Current coverage, whether local or national, will remain unchanged. .

2. Non-coverage. The medical evidence is not adequate to conclude that the item or service is reasonable and necessary under section 1862(a)(1)(A) and coverage is not allowed for Medicare beneficiaries.

3. Coverage without special conditions. The medical evidence is adequate to conclude that the item or service is reasonable and necessary under section 1862(a)(1)(A) for all Medicare beneficiaries.

From: Rollins, James (CMSjOCSQ) Sent: Friday, December 10, 2010 9:41 AM To: Jacques, Louis B. (CMSjOCSQ); Syrek Jensen, Tamara S. (CMSjOCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ)i Pencek, Eileen (CMS/OCSQ) Subject: Provenge

Louis, the draft NCO for provenge is moving along and we anticipate handing it to you by the next week. Though the IMPACT study does show a 4.1 month improvement in survival for the provenge group compared to the control group, there is some question about the study, including the comparator group. Also though the MEDCAC committee noted that patients had better survival in the provenge group, they had concerns about gaps in evidence.

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(b)(5) - Predecisional Obtained by Judicial Watch, Inc. via FOIA




From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, December 14,20101:44 PM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ashby, Lori M.

(CMS/OCSQ) Subject: CAG00422N Draft DM 1121410.docx Attachments: CAG00422N Draft DM 1 121410.docx

Jim:

Attached please find a draft decision memo for the PROVENGE® NCA. You will note that the only incomplete section is the MEDCAC summary. The reason this is not complete is that Eileen wanted to verify text in the summary with text in the draft transcript, which we received late last Thursday. Due to Eileen's work schedule and her relocation this week she did not finish this section yet. I will check with Eileen tomorrow as to when she will have the MEDCAC section complete.

Please let us know if you would like us to incorporate or address specific topics prior to sending it to Louis.

Leslye

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, December 15,20106:21 PM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ashby, Lori M.

(CMS/OCSQ) Subject: Re: CAG00422N Draft DM 1 121410.docx

I will make the corrections. Thanks

Sent from my iPhone

On Dec 15,2010, at 4:29 PM, "Rollins, James (CMS/OCSQ)" <[email protected]> wrote:

Sorry, I also forgot page 9 (same errors). Jarollins

From: Fitterman, Leslye (CMS/OCSQ) Sent: Tuesday, December 14, 2010 1:44 PM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) Subject: CAG00422N Draft DM 1121410.docx

Jim:

Attached please find a draft decision memo for the PROVENGE® NCA. You will note that the only incomplete section is the MEDCAC summary. The reason this is not complete is that Eileen wanted to verify text in the summary with text in the draft transcript, which we received late last Thursday. Due to Eileen's work schedule and her relocation this week she did not finish this section yet. I will check with Eileen tomorrow as to when she will have the MEDCAC section complete.

Please let us know if you would like us to incorporate or address specific topics prior to sending it to Louis.

Leslye

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, December 22,201010:50 AM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: CAG00422N Draft OM 2 122210.docx Attachments: CAG00422N Draft OM 2 122210.docx

Jim:

Here is the revised Draft OM. Please note thatthe yellow highlighted sections denote changes (as per your comments) and additions that were inadvertently omitted in the previous version you reviewed. It is also saved on the G drive.

leslye

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(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional


Leslye

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, December 22, 20102:12 PM To: Rollins, James (CMS/OCSQ) Cc: PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: DRAFT OM 122210.docx Attachments: DRAFT OM 122210.docx

Jim:

The attached is a clean document that has been saved on the G'drive.

Leslye

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From: Jacques, Louis B. (CMS/OCSQ) Sent: Wednesday, December 22,20102:59 PM To: Rollins, James (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ) Subject: Provenge DRAFT DM 122210 Ibj.docx Attachments: Provenge DRAFT DM 122210 Ibj.docx

Am still reading, looking pretty good so far. Please see comments in Section I about the wording of some of the conditions.

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(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisionalional




(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional(b)(5) - Predecisional


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From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, January 03, 2011 4:44 PM To: Meister, Mike (HHS/OGC) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen

(CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ)

Subject: ProvengeDRAFT OM 010311 Ibj to OGC.docx Attachments: Provenge DRAFT OM 010311 Ibj to OGC.docx

Mike,

Provenge PDM attached. I intentionally left a comment for your consideration n redline. We'll also send officially through Barb. Thanks.

Louis

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Rollins, Jarnes (CMS/OCSQ)

From: Jacques, Louis B. (CMS/OCSQ) Sent: Tuesday, January 04, 2011 11: 13 AM To: Caplan, Stuart (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

PASERCHIA, LORI A (CMS/OCSQ) . Subject: FW: Provenge DRAFT OM 010311 Ibj to OGC.docx

Just spoke with Mike, who feels Bill Parham should be included in the conversation. Seems reasonable, Bill is generally helpful.

From: Jacques, Louis B. (CMS/OCSQ) Sent: Monday, January 03, 2011 4:44 PM To: Meister, Mike (HHS/OGC) Cc: Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A. (CMS/OCSQ); Ashby, Lori M. (CMS/OCSQ) Subject: Provenge DRAFT DM 010311lbj to OGC.docx

Mike,

Provenge PDM attached. I intentionally left a comment for your consideration n redline. We'll also send officially through Barb. Thanks.

Louis

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From: Ashby, Lori M. (CMS/OCSQ) Sent: Wednesday, January 05, 2011 10: 13 AM To: Fisher, Barbara (HHS/OGC) Cc: Meister, Mike (HHS/OGC); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S.

(CMS/OCSQ); Rollins, James (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); PASERCHIA, LORI A (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ)

Subject: Provenge DRAFT DM 0103111bj to OGC.docx Attachments: Provenge DRAFT DM 010311 Ibj to OGC.docx

Barb-

Attached for OGC review is the draft Provenge POM. We would appreciate OGC review by January 18 so we can brief OA atan upcoming OCSQ Issues meeting.

Lori M. Ashby

Special Assistant OCSQ/Coverage and Analysis Group 410786"6322 [email protected]

Notice: The contents of this message and any attachments may be privileged and confidential. Please do not disseminatc without the approval of the Centers for Medicare &1; Medicaid Services. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy, forward, disseminate. or otherwise usc the infon11ation. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.

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From: Syrek Jensen, Tamara S. (CMS/OCSQ) Sent: Wednesday, January 19, 2011 12:46 PM To: Rollins, James (CMS/OCSQ) Subject: FW: provenge proposed dm Attachments: provengepdm.wpd

Tamara Syrek Jensen Deputy Director Coverage and Analysis Group Office of Clinical Standards and Quality, CMS 7500 Security Blvd. Baltimore, MD 21244 (410) 786-3529 [email protected]

From: Meister, Mike (HHS/OGC) Sent: Wednesday, January 19, 2011 12:23 PM To: Lee, Doris (HHS/OGC) Cc: Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Fitterman, Leslye (CMS/OCSQ); Paserchia, Lori A. (CMS/OCSQ); Warren, John F. (CMS/CMM) Subject: provenge proposed dm

Doris,

Please put in final.

Lawrence M. Meister Attorney Office of the General Counsel Department of Health and Human Services Room C2-05-23 7500 Security Boulevard Baltimore, MD 21244-1850

Phone (410) 786-5300 Fax (410) 786-5187 [email protected]

Notice: The contents of this message and any attachments may be privileged and confidential. Please do not disseminate without the approval of the Office of the General Counsel. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do notprint, copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Wednesday, January 19,201112:52 PM To: Meister, Mike (HHS/OGC) Cc: Salhus, Mary (HHS/OGC); Garver, Jennifer (HHS/OGC); Fisher, Barbara (HHS/OGC);

Hoffman, Janice (HHS/OGC); Jacques, Louis B. (CMS/OCSQ); Syrek Jensen, Tamara S. (CMS/OCSQ); Rollins, James (CMS/OCSQ)

Subject: RE: Can you send us the 10 public comments from law firms related to provenge that are mentioned on page 29?

Attachments: Public comments from attorneys on Provenge NCO .docx

Please find attached the document of the comments from attorneys on the PROVENGE NCA. Please note that there are seven attorneys. One of the seven attorneys submitted 4 comments. Thus, there were a total of 10 comments.

From: Meister, Mike (HHSjOGC) Sent: Wednesday, January 19, 2011 10:32 AM To: Fitterman, Leslye (CMSjOCSQ) Cc: Salhus, Mary (HHSjOGC); Garver, Jennifer (HHSjOGC); Fisher, Barbara (HHSjOGC); Hoffman, Janice (HHSjOGC) Subject: Can you send us the 10 public comments from law firms related to provenge that are mentioned on page 29?

Lawrence M. Meister Attorney Office of the General Counsel Department of Health and Human Services Room C2-05-23 7500 Security Boulevard Baltimore, MD 21244-1850

Phone (410)786-5300 Fax (410) 786-5187 [email protected]

Notice: The contents of this message and any attachments may be privileged and confidential. Please do not disseminate without the approval of the Office of the General Counsel. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.

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Notice: The contents of this message and any attachments may be privileged and confidential. Please do not disseminate without the approval of the Office of the General Counsel. If you are not an intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that you have received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.

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From: Berliner, Elise (AHRQ) Sent: Monday, January 24,2011 3:04 PM To: Fitterman, Leslye (CMS/OCSQ); Rollins, James (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ);

Paserchia, Lori A. (CMS/OCSQ) , Cc: . Wittenberg, Kim (AHRQ/COE) Subject: FW: Sipuleucel-T Final Deliverables Attachments: CANP061 O_Disposition of Comments_012011.doc; CANP061 0_ Outcomes of Sipuleucel

T _draft and appendixes_012011_FINAL.doc; CANP061 O_References with PMID_ 012011.docx

Hi CMS team,

Attached are the deliverables for the Provenge TA . Please let us know if you have any questions or comments on the TA or if you approve as final.

Also attached are the disposition of comments, I think some of the responses need to be less terse, but the scientific essence of the response is here.

What is your timeline going forward? As a reminder, CMS usually posts the final TA, and the AHRQ website links to the CMS site. AHRQ posts the dispostion of comments on the AHRQ site within 3 months of when the 'final is posted. Are you planning to post the final T A before the draft decision?

Also, part of the deliverable is a copy of all the articles used in the TA. Attached is the list of articles, Kimwill work with our library to get you the articles. But as time is short here, let us know if there are some that are especially critical for you, and we will try to get these ASAP.

Thanks, Elise

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From: Fitterman, Leslye (CMS/OCSQ) Sent: Friday, January 28,2011 12:26 PM To: Syrek Jensen, Tamara S. (CMS/OCSQ); Jacques, Louis B. (CMS/OCSQ) Cc: Rollins, James (CMS/OCSQ); Paserchia, Lori A. (CMS/OCSQ); Pencek, Eileen (CMS/OCSQ) Subject: Provenge_DRAFT_DM_0128_0GC_response3 LP rev (2).docx Attachments: Provenge_DRAFT_DM_0128_0GC_response3 LP rev (2).docx

Attached please find the latest version of PDM. Look forward to your comments and suggestions

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Page 1 of 18Drug details - MICROMEDEX® 2.0

51 ULEU Eva!uations

1) Class a) This drug is a member of the following classCes):

Immunological Agent

2) Dosing Information

a) Adult

1) Hormone refractory prQstate cancer, Metastatic

a) one dose IV over 60 min given approximately every 2 wk for 3 doses; each dose contains a minimum of 50 million autologous CD54+ cells in 250 mL lR and is activated with prostatic acid phophatase linked to granulocyte-macrophage stimulating factor; peripheral blood mononuclear cells are obtained via leukapheresis approximately 3 days prior to each infusion; premedicate patients with acetaminophen and an antihistamine Ceg, diphenhydramine) 30 min prior to dose (Prod Info PROVENGE(R) suspension for IV infusion, 2010)

3) Contraindications

a) specific contraindications have not been determined (Prod Info PROVENGE(R) suspension for IV infusion, 2010)

4) Serious Adverse Effects

a) Adverse reaction to drug or medicament administered by infusion, Grade 3 b) Cerebrovascular accident . c) Eosinophilia ' d) Myasthenia gravis e) Myositis f) Rhabdomyolysis g) Tumor flare

5) Clinical Applications

a) FDA Approved Indications

1) Hormone refractory prostate cancer, Metastatic

A) Information on specific products and dosage forms can be obtained by referring to the Tradename list (Product Index) B) Synonyms

Sipuleucel-T

"

http://www.thomsonhc.com/micromedex2/1ibrarian/PFDefaul tActionld/evidencexpert.Int... 01/07/2011


Drug details - MICROMEDEX® 2.0 Page 2 of 18

Storage and Stability

A) Preparation

1) General Information

a) Use proper procedures for the handling and disposal of leukapheresis materials and sipuleucel-T(Prod Info PROVENGE(R) suspension for IV infuSion, 2010). 2) Intravenous route

a) After removing the sipuleucel-T infusion bag from the insulated container, use within 3 hours at room temperature. Consult cell product disposition form and product label prior to infusion. Do not initiate infusion of expired sipuleucel-T. Prior to administration, gently mix the infusion bag contents (slightly cloudy with cream-to-pink color) and disperse small clumps of cellular material. Do not administer sipuleucel-T if clumps remain in the bag after mixing. Administer the entire contents of infusion bag IV over 60 minutes; do not use a cell filter (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

B) Infusion, intravenous

1) Suspension

a) Keep in the insulated polyurethane infusion bag until the time of administration; do not remove the infusion bag from the outer shipping box until patient is ready for infusion (Prod Info PROVENGE(R) suspension for IV infusion, 2010). b) Once removed from the insulated bag, suspension is stable at room temperature for up to 3 hours (Prod Info PROVENGE(R) suspension for IV infuSion, 2010).

Adult Dosage

Normal Dosage Intravenous route

Hormone refractory prostate cancer, Metastatic a) Premedication

1) Premedicate patients with acetaminophen and an antihistamine (eg, diphenhydramine) 30 minutes prior to each sipuleucel-T dose to minimized theriskof acute infusion reactions (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

b) Dosing 1) For the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer, the recommended dosage of sipuleucel-T is one dose intravenously over 60 minutes given approximately every 2 weeks for 3 complete doses. Each dose contains a minimum of 50 million autologous CD54+ cells in 250 milliliters of lactated Ringer injection and is activated with prostatic acid phophatase linked to granulocyte-macrophage stimulating factor. ~eripheral blood mononuclear cells are obtained from each patient by leukapheresis approximately 3 days prior to sipuleucel-T infusion. If a scheduled sipuleucel-T dose is not received, the patient must undergo an additional leukapheresis procedure to continue treatment (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

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· . -'


Dosage in Other Disease States A) Acute Infusion Reaction 1) Temporarily stop or slow the sipuleucel-T infusion if patients develop an acute infusion reaction (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

A) specific contra indications have not been determined (Prod Info PROVENGE(R) suspension for IV infusion, 2010)

Precautions

A) acute infusion reactions (eg, fever, chills, nausea, vomiting, dyspnea, hypoxia, bronchospasm, and hypertension) have been reported, with some cases requiring hospitalization; closely monitor patients with cardiac and pulmonary conditions; decrease the infusion rate or discontinue the infusion if necessary (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 8) final sterility test results of product may not be available prior to sipuleucel-T infusion; microbial contamination may be reported after infusion (Prod Info PROVENGE(R) suspension for IV infusion, 2010) C) health care professionals; risk of exposure to transmissible infectious diseases present in leukapheresis material; use proper precautions when handling the product (Prod Info PROVENGE(R) suspension for IV infusion, 2010) D) report suspected adverse reactions to the Dendreon Corporation at 1-877-336-3736 or the US Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch (Prod Info· PROVENGE(R) suspension for IV infusion, 2010) .

. Adverse·Reac:tions

Cardiovascular Effects Hypertension

1) Incidence: 7.5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure; hypertension occurred in 7.5% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 4.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Dermatologic Effects Rash

1) Incidence: 5.2% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic



·, Drug details - MICROMEDEX® 2.0 Page 4ofl8

castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, rash occurred in 5.2% of patients scheduled to receive 3 sipuleucel-T inf~sionsat 2-week intervals (n=601) compared with 3.3% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Sweating

1) Incidence: 5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, sweating occurred in 5% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 1% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Gastrointestinal Effects Nausea

1) Incidence: 21.5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, nausea occurred in 21.5% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 14.9% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).,' .

Vomiting 1) Incidence: 13.3% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, vomiting occurred in 13.3% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 7.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Hematologic Effects Anemia

1) Incidence: 12.5% (Prod Info PROVENGE(R) suspension for IV 1nfusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who . underwent at least one leukapheresis procedure, anemia' occurred in 12.5% of

. patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 11.2% of patients who received non..,activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Eosinophilia 1) One case of eosinophilia was reported with sipuleucel-T therapy in controlled clinical trials (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

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Immunologic Effects Sepsis

1) In a multicenter, randomized, double-blind controlled trial (n=512), sepsis was reported in asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer patients who received sipuleucel-T through a central venous catheter. Patients with central venous catheters receiving sipuleucel-T should be monitored for infectious sequelae (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Musculoskeletal Effects Backache

1) Incidence:' 29.6%' (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized/ controlled trials in patients with metastatic castrate~resistant or non-metastatic androgen-dependent prostate cancer who underwent at least o'ne leukapheresis procedure, back pain occurred in 29.6% of patients scheduled to receive 3sipuleucel-T infusions at i-week intervals (n=601) compared with 28.7% of patients who received non-activated autologous peripheral blood mononuclearcells(n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Myalgia .' ...

1) Incidence: 11.8% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent atleast oneleukapheresis procedure, muscle'pain occurred in 11.8% of patients scheduled to receive 3 sipuleutel-T infusions at 2-week intervals (n=601) compared with 5.6% of patients who· received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Myasthenia gravis 1) One case of myasthenia gravis was reported with sipuleucel-T therapy in controlled clinical trials (prod Info PROVENGE(R) suspension for IV infUSion, 2010).

Myositis "

1) One case of myositis was reported with sipuleucel-T therapy in controlled clinical trials (Prodlnfo PROVENGE(R) suspension for IV infusion, 2010).

Neck pain 1) Incidence: 5.7% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic

, castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, neck pain occurred in 5.7% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 4.6%.ofpatients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Rhabdomyolysis 1) One case of rhabdomyolysis was reported with sipuleucel-T therapy in controlled clinical trials (Prod Info PROVENGE(R) suspension for IV infUSion, 2010).

Spasm

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Drug details -MICROMEDEX® 2.0 Page 6 of 18

1) Incidence: 7.7% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, muscle spasm occurred in 7.7% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 5.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Neurologic Effects Asthenia

1) Incidence: 10.8% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, asthenia occurred in 10.8% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 6.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Cerebrovascular accident 1) Incidence: 3.5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, hemorrhagic and ischemic stroke occurred in 3.5% of patients scheduled to receive 3 sipuleucel-T infusions at 2week intervals (n=601) compared with 2.6% of patients who received nonactivated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Dizziness 1) Incidence: 11.8% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, dizziness occurred in 11.8% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 11.2% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Headache 1) Incidence: 18.1% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, headache occurred in 18.1% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 6.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Tremor 1) Incidence: 5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic

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.'


castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, tremor occurred in 5% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 3% of patients who received non-activated autologous peripheral blood mononuclear cells (n==303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010). 3) Tremor occurred in 9.8% of patients treated with sipuleucel-T (n=82) for asymptomatic, hormone-refractory, metastatic prostate cancer compared with no patients treated with placebo (n=45) in a double-blind, randomized, phase 3 clinical trial. All cases were grade 1 or 2 (Smallet ai, 2006).

Renal Effects Hematuria

1) Incidence: 7.7% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, hematuria occurred in 7.7% of patients scheduled to receive 3 sipuJeucel-T infusions at 2-week intervals (n=601) compared with 5.9% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Respiratory Effects Cough

1) Incidence: 5.8% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, cough occurred in 5.8% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 5.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Dyspnea ,:~

1) Incidence: 8.7% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, dyspnea occurred in 8.7% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 4.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infUSion, 2010).

Upper respiratory infection 1) Incidence: 6.3% (Prod Info PROVENGE(R) suspension for IV infUSion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, upper respiratory tract infection occurred in 6.3% of patient,S scheduled to receive 3 sipuleucel-T infusions at 2week intervals (n=601) compared with 5.9% of patients who received non




activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Other Adverse reaction to drug or medicament administered by infusion, All grades

1) Incidence: 71.2% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) Acute infusion reactions have occurred within 1 day of sipuleucel-T therapy. The most common events reported include fever,chills, respiratory events (dyspnea, hypoxia, and bronchospasm), tachycardia, hypertension, nausea, vomiting, and. fatigue. In most patients (95.1 %) the reaction was described as mild to moderate. Fever and chills usually resolved within 2 days. Premedicate patients with acetaminophen and an antihistamine (eg, diphenhydramine) 30 minutes prior to sipuleucel-T to minimize the risk of infusion reactions. Patients with pulmonary and cardiac conditions should be closely monitored. Decrease the infusion rate or discontinue the infusion if necessary. Acetaminophen, intravenous H 1- or H2blocking agents, and low-dose intravenous meperidine have been used to treat infusion reactions in clinical trials (Prod Info PROVENGE(R) suspension for IV infusion, 2010). 3) In controlled clinical trials, acute infusion reactions occurred in 71.2% of patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who received sipuleucel-T infusions (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Adverse reaction to drug or medicament administered by infusion, Grade 3 1) Incidence: 3.5% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) Grade 3 acute infusion reactions have occurred in patients who receive sipuleucel-T therapy, with some cases resulting in hospitalization. The most common events reported include chills, fever, asthenia, dyspnea, hypoxia, bronchospasm, nausea, vomiting, muscle ache, hypertension" headache, and dizziness. Severe events occurred more often following the second infusion comp,ared with the first infusion (2.1% vs 0.8%, respectively). Premedicate patients with acetaminophen and an antihistamine (eg, diphenhydramine) 30 minutes prior to sipuleucel-T to minimize the risk of infusion reactions. Patients with pulmonary and cardiac conditions should be closely monitored. Decrease the infusion rate or discontinue the infusion if necessary. Acetaminophen, intravenous H1- or H2-blocking agents, and low-dose intravenous meperidine have been used to treat infusion reactions in clinical trials (Prod Info PROVENGE(R) suspension for IV infusion, 2010). 3) In controlled clinical trials, grade 3 acute infusion reactions occurred in 3.5% of patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who received sipuleucel-T infusions (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Citrate adverse reaction 1) Incidence: 14.8% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-reSistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, citrate tOXicity occurred in 14.8% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 14.2% of patients who received non-activated autologous

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peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Fatigue 1) Incidence: 41.1% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, fatigue occurred in 41.1% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 34.7% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Feels cold 1) Incidence: 8.5% (Small et ai, 2006) 2) Feeling cold occurred in 8.5% of patients treated with sipuleucel-T (n=82) for asymptomatic, hormone-refractory, metastatic prostate cancer compared with no patients treated with placebo (n=4s) in a double-blind, randomized, phase 3 clinical trial. All cases were grade 1 or 2 (Small et ai, 2006).

Fever 1) Incidence: 31.3% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, fever occurred in 31.3% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 9.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n:::;:303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010). 3) Pyrexia, primarily as part of ·infusion-related reactions, occurred in 29.3% of patients treated with sipuleucel-T (n=82) for asymptomatic, hormone-refractory, metastatic prostate cancer compared with 2.2% of patients treated with placebo (n=4s) in a double-blind, randomized, phase 3 clinical trial. Grade 3 or 4 cases accounted for 2.4% (Small et ai, 2006).

Influenza-like symptoms 1) Incidence: 9.7% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, influenza-like illness occurred in 9.7% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 3.6% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Pain 1) Incidence: 12.3% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, pain occurred in 12.3% of patients scheduled to receive 3 sipuleucel~T infusions at 2-week intervals (n=601) compared with 6.6% of patients who received non-activated autologous peripheral

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blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Rigor 1) Incidence: 59.8% (Small et ai, 2006) . 2) Rigors, primarily as part of infusion-related reactions, occurred in 59.8% of patients treated with sipuleucel-T (n=82) for asymptomatic, hormone-refractory, metastatic prostate cancer compared to 8.9% of patients treated with placebo (n=45) in a double-blind, randomized,phase 3 clinical trial. Grade 3 or 4 cases accounted for 4.9% (Small et ai, 2006).

Shivering 1) Incidence: 53.1% (Prod Info PROVENGE(R) suspension for IV infusion, 2010) 2) In pooled results from 4 randomized, controlled trials in patients with metastatic castrate-resistant or non-metastatic androgen-dependent prostate cancer who underwent at least one leukapheresis procedure, chills occurred in 53.1% of patients scheduled to receive 3 sipuleucel-T infusions at 2-week intervals (n=601) compared with 10.9% of patients who received non-activated autologous peripheral blood mononuclear cells (n=303) (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Tumor flare 1) One case of tumor flare was reported with sipuleucel-T therapy in controlled clinical trials (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

A) Teratogenicity/Effects in Pregnancy

1) Thomson Pregnancy Rating: Fetal risk cannot be ruled out.

a) Available evidence is inconclusive or is inadequ'ate for determining fetal risk when used in pregnant women or women of childbearing potential. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during pregnancy.

See Drug Consult reference: ~=~...::..="--'-'="'-.o.,.=~=~= 2) Crosses Placenta: Unknown 3) Clinical Management

a) Sipuleucel-T is indicated for the treatment of prostate cancer (Prod Info PROVENGE(R) suspension for IV infusion, 2010). Therefore, no data are available regarding the effects of this drug during pregnancy.

B) Breastfeeding 1) Thomson Lactation Rating: Infant risk cannot be ruled out.

a) Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding. 2) Clinical Management

a) Sipuleucel-T is indicated for the treatment of ~rostate cancer (Prod Info PROVENGE(R) suspension for IV infusion, 2010). Therefore, no data are available regarding the effects of this drug during lactation.

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Mo.nito:ri;ngPa.rameters ~,~ ~"'" ,,~-

A) Therapeutic

1) Physical Findings

a) No specific monitoring has been determined.

8) Toxic

1) Physical Findings

a) Closely monitor patients with cardiac or pulmonary conditions for acute infusion reactions (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

Patie.ntlnstructions

A) Sipuleucel-T (Injection)

Sipuleucel-T

Treats advanced prostate cancer. This medicine is made from your own immune cells (autologous cellular immunotherapy). .

When This Medicine Should Not Be Used: You should not receive this medicine if you have had an allergic reaction to sipuleucel-T.

How to Use This Medicine: Injectable

Your doctor will prescribe your exact dose and tell you how often it should be given. This medicine is given through a needle placed in one of your veins. You will receive this medicine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you this medicine. Your doctor will tell you to have your immune cells collected three days before each scheduled infusion of this medicine. Your collected cells are mixed with a protein to make them ready for your infusion. The medicine is usually'given as 3 doses, spaced 2 weeks apart. This medicine must be given slowly, so the needle will remain in place for one hour. You may also receive acetaminophen (Tylenol®) and diphenhydramine (Benadryl®) to help prevent possible infusion reactions.

If a Dose is Missed:

It is very important that you receive all doses of this medicine. Try to keep all scheduled appointments. If you miss a dose, your medicine will not be usable. Your doctor will work with you to schedule a new appointment at the cell collection center. You may also get a new appointment for your infusion.

Drugs and Foods to Avoid: Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

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Make sure your doctor knows if you are receiving a treatment or using a medicine that causes a weak immune system. This may include radiation therapy, cancer medicines, or steroid medicines (such as cortisone, dexamethasone, prednisone, Cortef®, or Medrol®).

Warnings While Using This Medicine:

Make sure your doctor knows if you have heart disease, heart rhythm problems, lung disease or breathing problems, or a history of stroke. This medicine may cause fever; chills; dizziness; joint pain; fast heartbeat; nausea and vomiting; shortness of breath; troubled breathing; or unusual tiredness or weakness within a few hours after you receive it. Check with your doctor or nurse right away if you have any of these symptoms. Call your doctor right away if you start to have a cough, weight loss, fever, or redness or pain at the infusion or collection sites. These may be signs that you have an infection. Check with your doctor right away if you have chest pain or discomfort, dizziness, fainting, pounding or rapid pulse, or fast, slow, or uneven heartbeat. These, maybe symptoms ofa heart rhythm problem. Your doctor will need to check your progress at regular visits while you are using this medicine. Be sure to keep all appointments.

Possible Side Effects While Using This Medicine: Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing. Change in how much or how often you urinate, bloody or cloudy urine, or painful urination. Chest pain, fast or uneven heartbeat. Fever, chills, cough, runny nose, sore throat, and body aches. Numbness, tingling, or burning pain in your hands, arms, legs, or feet. Pain, itching, burning, swelling, or a lump under your skin where the needle is placed. Shortness of breath or troubled breathing. Swelling in your hands, ankles, or feet. Unusual bleeding or bruising. Unusual tiredness or weakness.

If you notice these less serious side effects, talk with your doctor:

Back, bone, joint, or muscle pain. Constipation, diarrhea, nausea, or vomiting. Decreased weight. Dizziness or headache. Loss of appetite. Skin rash. Trouble sleeping. Warmth or redness in your face, neck, arms, or upper chest.

If you notice other side effects that you think are caused by this medicine, tell your doctor.

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.··Plac~lf1'"rherapy ~~_~~~ • ·V~

A) Sipuleucel-T (APC8015, Provenge(R)) is a treatment vaccine containing a fusion protein that is combined ex vivo with autologous dendritic cells, obtained via leukapheresis, and reinfused into the patient to create an immune response targeted towards prostatic cancer cells (Small et ai, 2000; Rini et ai, 2006). The fusion protein, PA2024, consists of recombinant prostatic acid phosphatase (PAP), an antigen located only in prostate tissue, fused with granulocytemacrophage-colony stimulating factor (GM-CSF) (Small et ai, 2006). Sipuleucel-T improved overall survival in patients in patients with asymptomatic, or minimally symptomatic hormonerefractory, metastatic prostate cancer in 2 multicenter, randomized, double-blind, controlled phase 3 trials; however, time to disease progression was not significantly different with sipuleucel-T treatment compared with control in either trial (Small et ai, 2006; Prod Info PROVENGE(R) suspension for IV infusion, 2010).

A) Mechanism of Action

- 1) Prostatic acid phosphatase (PAP) is an antigen expressed in prostate cancer tissue. Sipuleucel-T is autologous cellular immunotherapy that includes antigen presenting cells (A PC) that have been activated by a recombinant human protein consisting of PAP linked with granulocyte-macrophage colony stimulating factor (PAP-CM-CSF). Three days prior to the infusion date, the patient's peripheral blood mononuclear cells are obtained by standard leukapheresis. During ex vivo culture, PAP-GM-CSF binds to the APCs and is processed into smaller protein fragments that are displayed on the surface of the APe. Although the exact mechanism of action of sipuleucel-T is unknown, the therapy is thought to induce an immune response against PAP (Prod Info PROVENGE(R) suspension for IV infusion, 2010).

! "rt1¢f'apeutic,U&es

Hormone refractory prostate cancer, Metastatic FDA Labeled Indication 1) Overview

FDA Approval: Adult, yes; Pediatric, no.

Efficacy: Adult, Evidence favors efficacy

Recommendation: Adult, Class IIa

Strength of Evidence: Adult, Category B

See Drug Consult reference: RECOMMENDATION ,"'ND EVIDENCE RATINGS 2) Summary:

Sipuleucel-T is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer (Prod Info PROVENGE(R) suspension for IV infusion, 2010). Sipuleucel-Timproved overall survival in patients in patients with asymptomatic, hormone-refractory, metastatic prostate cancer in 2 multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials; however, time to disease progression was not

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Drug details - MICROMEDEX® 2.0 Page 14 0f 18

significantly different with sipuleucel-T treatment compared with placebo in either trial (Small et ai, 2006; Prod Info PROVENGE(R) suspension for IV infusion, 2010).

3) Adult:

a) Ina multicenter, randomized, double-blind; phase 3 trial (n=512), treatment with sipuleucel-T significantly improved overall survival (OS) compared with placebo in patients with asymptomatic or minimally symptomatic metastatic castrate-resistant. (hormone-refractory) prostate cancer. Patients (median age, 71 years (yr); primary Gleason scores of 4 or more, 58%) with progressive, metastatic disease in the soft tissue (7%), bone (48%), or both (44%) and serum testosterone levels less than 50 nanograms/milliliter were randomized 2:1 to receive sipuleucel-T (n=341) or control (n=171) as an infusion for 3 doses approximately 2 weeks apart (on weeks 0, 2, and 4) about 3 days after leukapheresis. The control infusion was autologous peripheral blood mononuclear cells that had not been activated with prostatic acid phophatase linked to granUlocyte-macrophage stimulating factor. Prior treatment consisted of radical prostatectomy (35%), local radiotherapy (54%), and chemotherapy (18%) including docetaxel. Bisphosphate therapy was administered in 48% of study patients. Median OS was 25.8 months (mo) (95% confidence interval (CI), 22.8 to 27.7 mo) in patients who received sipuleucel-T and 21.7 mo (95% CI, 17.7 to 23.8 mo) in patients who received placebo (adjusted hazard ratio, 0.775; 95% CI, 0.614 to 0;979; p=0.032). Time to disease progression was not significantly different between the 2 study arms. Median survival of patients 65 yr ofage or older was 23.4 mo (95% CI, 22 to 27.1) compared to 17.3 mo (95% CI, 13.5 to 21.5) in the placebo group. (Prod I~fo PROVENGE(R) suspension for IV infusion, 2010). b) Sipuleucel-T improved overall survival (OS) but not time to progression CTTP) in patients with asymptomatic, hormone-refractory, metastatic prostate cancer in a doubleblind, placebo-controlled, randomized, phase 3 clinical trial. Patients (n= 127) with progressive, metastatic adenocarcinoma of the prostate, serum testosterone levels less than 50 nanograms (ng)/deciliter, and positive immunohistochemistry staining for prostatic acid phosphatase (PAP) in at least 25% of cells were randomized 2: 1 to sipuleucel-T intravenously over 30 minutes on weeks 0, 2, and 4 (n=82; median age, 73 years; range, 47-85 years) or placebo (n=45; median age, 71 years; range, 50 to 86 years). Luteinizing hormone-releasing hormone agonist was continued in patients without prior bilateral orchiectomy. The median number of nucleated cells per infusion in the sipuleucel-T group was 3.65 x 10(9) while the median humber of C054+ bright cells was 7.45 x 10(8) per infusion. Premedications consisted of acetaminophen 650 milligrams (mg) and diphenhydramine 50 mg. Bisphosphonate therapy was allowed if started greater than 30 days prior to registration. At baseline, bone involvement between groups was similar (sipuleucel-T, 93.9%; placebo, 91.3%) but bone-only disease was present in 42.7% versus (vs) 26.7% and greater than 10 bone lesions were present in 40.2% and 26.7% of the sipuleucel-T and placebo groups, respectively. In addition, 3.7% of patients in the sipuleucel-T group had prior chemotherapy compared with 8.9% of the placebo group. Median baseline Gleason score was 7 in each group while median baseline prostate specific antigen level was 46 nanograms/milliliter (ng/mL) (range, 3.5 to 3621 ng/mL) in the sipuleucel-T group and 47.9 ng/mL (range, 7.9 to 2799 ng/mL) in the placebo group. The intent-to-treat population was analyzed for both efficacy and safety. Median TTP, the primary endpoint, was not statistically different between groups {sipuleucel-T, 11.7 weeks; 95% confidence interval (CI), 9.1 to 16.6 weeks; placebo, 10 weeks; 95% CI, 8.7 to 13.1 weeks; hazard ratio (HR), 1.45; 95% CI, 0.99 to 2.11; p=O.052). Median OS was 25.9 months (95% CI, 20 to 31.9 months) in patients who received sipuleucel-T and 21.4 months (95% CI, 12.3 to 25.8

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months) in patients who received placebo (HR, 1.7; 95% CI, 1.13 to 2.56; p=O.Ol). Overall survival at 36 months, which included 34 patients from the placebo group who were subsequently treated with open-label sipuleucel-T, was also significantly improved in the' sipuleucel-T arm (34%) compared to the placebo arm (11%; p=0.005) and remained statistically significant after correcting for baseline prognostic factors (HR, 2.12; 95% CI, 1.31 to 3.44; p less than 0.002). The median ratio of the T-cell stimulation index at 8 weeks compared to baseline was 8-fold higher in the sipuleucel-T arm (16.91) versus the placebo arm (1.99; p less than 0.001). Adverse events that were Significantly (p equal to or less than 0.05) more common in the sipuleucel-T arm included rigors (59.8% vs 8.9%), pyrexia (29.3% vs 2.2%), tremor (9.8% vs 0%), and feeling cold (8.5% vs 0%). Grade 30r 4 toxicities in the sipuleucel-T arm were not common but included rigors (4.9%), dyspnea (4.9%), pyrexia (2.4%), back pain (2.4%), anemia (2.4%), extremity pain (1.2%), and arthralgia (1.2%) (Small et ai, 2006). c) APC8015 (Provenge(R» followed by PA2024 produced one durable clinical response in 19 patients with progressive, androgen-independent, metastatic prostate cancer in a preliminary phase 2 clinical trial. Patients (n=21; median age, 72 years; range, 57-83 years) with metastatic prostate cancer that progressed either radiologically or biochemically despite androgen ablation and antiandrogen withdrawal were required to have baseline prostate specific antigen (PSA) levels of 5 nanograms/milliliter (ng/mL) or greater (median baseline PSA, 221 ng/mL; range, 21-1147 ng/mL) and were allowed to have received previous chemotherapy or radiotherapy. APC8015 (consisting of the fusion protein, PA2024, combined with antigen presenting cells from each patient) was administered approximately 48 hours after leukapheresis with the maximum number of cells manufactured (median, 2.7 x 10(9) cells, first infusion; 3.2 x 10(9), second infusion) intravenously over 30 minutes on weeks 0 and 2. Patients were monitored for 30 minutes after each infusion. PA2024 0.5 milligrams subcutaneously in each thigh was administered at weeks 4, 8, and 12. Gonadal androgen suppression was continued. Two patients were not evaluable for response due to disease progression occurring prior to the first PA2024 injection. Median time to progression was 118 days. One patient expe~ienced an impressive PSA response with a ba'seline PSA of 221 ng/mL that initially rose to 251 ng/mL at week 4, but then dropped to undetectable levels by week 24 and remained undetectable for 52 monttis after starting treatment. This patient also experienced resolution in metastatic adenopathy and was the only patient who experienced any radiographic improvement. Two additional patients achieved transient reductions in PSA of 25% to 50%~ although one was during tumor progression. Treatment was well tolerated with the most Gommon adverse events consisting of chills (,17 of 42 infusions) and fever (9 of 42 infusions). Most adverse events were grade 1 or 2. Grade 4 events after APC8015 consisted of dyspnea (n=l) and vomiting (n=l) while one case of grade 4 fatigue was noted after PA2024 injections (Burch et ai, 2004).

Prostate cancer, Biochemically-relapsed, andrOgen-de,P~rdent 1) Overview •~

FDA Approval: Adult, no; Pediatric, no J1~ ~ ( Efficacy: Adult, Evidence is inconclusive 0' U~, reP ~!J-4 '" Recommendation: Adult, Class lIb (L(!,omm flO d. . \ 1"\ tjO

Strength of Evidence: Adult, category@)'

See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS

2) Summary:

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Did not effectively reduce prostate specific antigen (PSA) levels either alone (n= 19) (Beinart et ai, 2005) or in combination with bevacizumab (n=22), although the combination of sipuleucel-T and bevacizumab did significantly reduce PSA doubling time (Rini et ai, 2006) in small, phase 2 trials in patients with androgen-dependent, biochemically-relapsed prostate cancer

3) Adult:

a) The combination of sipuleucel-T and bevacizumab did not effectively reduce prostate specific antigen (PSA) levels but did significantly reduce PSA doubling time in patients with androgen-dependent, biochemically-relapsed prostate cancer in a small, phase 2 trial. Patients (n=22; median age, ,70 years; range, 55-79 years) with adenocarcinoma of the prostate who had evidence of prostate specific antigen (PSA) progression after definitive local therapy (prostatectomy, 23%; prostatectomy with salvage radiation therapy, 63%; radiation therapy, 14%) were treated with the maximum manufacturable dose of sipuleucel-T, estimated, at 12 x 10(9) nucleated cells/square meter (m(2)) (minimum dose, 3 x 10(6) dendritic cells), followed by bevacizumab 10 milligrams/kilogram intravenously on weeks 0, 2,and 4. Bevacizumab monotherapy was then continued every 2 weeks until disease progression or unacceptable toxicity. Exclusion criteria included metastatic disease, prior hormonal therapy for progressive disease" and any prior chemotherapy or immunotherapy. Premedication for sipuleucel-T consisted of acetaminophen 650 milligrams (mg) orally and diphenhydramine 50 mg orally. Baseline characteristics consisted of a median Gleason score of 7 (range, 5-9), a median PSA of 2.3 nanograms/milliliter (ng/mL) (range, 0.5-5.1 ng/mL), and a median PSA doubling time of 6.9 months (range, 1-32.6 months). The primary endpoint was PSA response (at least a 50% decrease in PSA compared to baseline). Accrual was terminated after 21 patients due to one patient achieving a PSA response (5%; 95% confidence interval, 0%-24%). After a median follow-up of 11.4 months, median time to PSA progression was 11.2 months. Nine patients achieved a decline in PSA ranging from 6% to 72%, with 3 of these patients having a PSA decline of at least 25%. Median PSA doubling time after treatment (12.7 months; range, 2-32.6 months) in 20 patients was significantly improved compared to baseline (p=O.Ol). The one responding patient had a baseline PSA of 2.7 ng/mL which roseto 5.6 ng/mL at week 12, then experienced a nadir PSA of 0.78 ng/mL at week 72, discontinued treatment at week 88 due to a proteinuria, and had a stable PSA off all treatment until week 108 (7 months following the last bevacizumab dose), at which time PSA progression was noted. Grade 1 or 2 infusion-related reactions due to sipuleucel-T consisted of rigors/chills (64%), myalgia (55%) and fever (41%). Grade 1 or 2 fatigue was noted in 82% of patients. Grade 3 toxicities consisted of one case each of hypertension, proteinuria, gastrointestinal bleeding, hypersensitivity, congestive heart failure, and cerebrovascular ischemia (Rini et ai, 2006). b) APC8015 (Antigen-Presenting Cells 8015; Provenge(R)) did not effe<:tively reduce prostate specific antigen (PSA) levels in patients with androgen-dependent, biochemically-relapsed prostate cancer in a small, phase 2 trial. Patients (n=19; median age, 67 years; range, 55-78 years) with stage Tl-3, NO-1, MO adenocarcinoma ofthe prostate, a median Gleason score of 7 (range, 4-9) and evidence of prostate specific antigen (PSA) progression after definitive local therapy (prostatectomy, 47.4%; prostatectomy with salvage radiation therapy, 36.8%; radiation therapy, 15.8%) were treated with the maximum manufacturable dose of APC8015 infused over 30 minutes, approximately 48 hours after leukapheresis. Premedication consisted of acetaminophen 650 milligrams (mg) orally and diphenhydramine 50 mg orally. Treatment was

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administered at weeks 0, 2, and 4 and each infusion contained approximately 1.2 x 10 (9) nucleated cells/square meter. Baseline median PSA level was 1.6 nanograms/milliliter (ng/mL) (range, 0.5-3.1 ng/mL). Enrollment was terminated after 19 patients due to no patient achieving at least a 50% decline in PSA. After a.median follow-up of 11 months (range, 1-47 months), mediantime to PSA progression was 11.7 months (range, 1-47 months) in 18 evaluable patients. Seven patients achieved a decline in PSA ranging from 6% to 33% while the remaining 11 patients experienced continued increasing PSA levels. Median PSA doubling time after treatment (noted from week 0 until PSA progression) was 7.9 months (range, 2.3-66.6 months) compared to 4.9 months (range, 2-22 months) at baseline (p=0.09). Substantial prolongation in PSA doubling time was observed in 2 patients. APC8015 waswell tolerated with grade 1 infusion-related reactions consisting of fever/chills (n=10) and fatigue/malaise (n=7). Grade 3 hypotension occurred in one patient but was not infusion-related and was not considered treatment-related (Beinart et ai, 2005).

1. Beinart G, Rini BI, Weinberg V,et al: Antigen-presenting cells 8015 (Provenge) in patients with androgen-dependent, biochemically relapsed prostate cancer. Clin Prostate Cancer . 2005; 4(1):55-60.

2. Burch PA, Croghan GA, Gastineau DA, et al: Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 triaIBURCH2004. Prostate 2004; 60(3):197-204.

3. Product Information: PROVENGE(R) suspension for IV infusion, sipuleucel-T suspension for IV infusion. Dendreon Corporation, Seattle, WA,2010.

4. Rini BI, Weinberg V, Fong L, et al: Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy. Cancer 2006; 107 (1):67-74.

5. Small EJ, Fratesi P, Reese DM, et al: Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin.Oncol 2000; 18(23):3894-3903. .

6. Small EJ, Schellhammer PF, Higano CS, et al: Placebo-controlled phase III trial of immunologic therapy with sipuleucel::..T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24(19):3089-3094. ,

Strength of Recommendation

Class I - Recommended

The given test or treatment has been proven to be useful, and should be performed or administered.

Class IIa - Recommended, In Most Cases

The given test, or treatment is generally considered to be useful, and is indicated in most cases.

Class lIb - Recommended, In Some Cases

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The 'given test, br treatment may,be useful, and is indicated in some, but not most, cases.

Class III - Not Recommended

The given test, or treatment is not useful, and should be avoided.

Class Indeterminate - Evidence Inconclusive

Str~ngth of Evidence

Category A

Category A evidence is based on data derived from: Meta-analyses of randomized controlled trials with homogeneity with regard to the directions and degrees of results between individual studies. Multiple, well-done randomized clinical trials involving large numbers of patients.

Category B

Category B evidence is based on data derived from: Meta-analyses of randomized controlled trials with conflicting conclusions with regard to the directions and degrees of results between individual studies. Randomized controlled trials that involved small numbers of patients or had significant methodological flaws (e.g., bias, drop-out rate, flawed analYSiS, etc.). Nonrandomized studies (e.g., cohort studies, case-control studies, observational studies).

CategoryC

Category C evidence is based on data derived from: Expert opinion or consensus, Ci;lse reports or case series.

No Evidence

Last Modified: May 12, 2010

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Drug summary - MICROMEDEX® 2.0 Page 1 of 9

Sipuleucel..T Summary

Aclult'Q.osj,mg ,"" --''''': ~).w~

• Hormone refractory prostate cancer, Metastatic: one dose IV over 60 min given approximately every 2 wk for 3 doses; each dose contains a minimum of 50 million autologous CD54+ cells in 250 mL LR and is activated with prostatic acid phophatase linked to granulocyte-macrophage stimulating factor; peripheral blood mononuclear cells are obtained via leukapheresis approximately 3 days prior to each infusion; premedicate patients with acetaminophen and an antihistamine (eg,· diphenhydramine) 30 min prior to dose ill

O()SeACljustmehts

• acute infusion reaction: interrupt or slow the infusion ill

• Hormone refractory prostate cancer, Metastatic

Contralndications

• specific contraindications have not been determined ill

I,

PrecaUtions

• acute infusion reactions (eg, fever, chills, nausea, vomiting, dyspnea, hypoxia, bronchospasm, and hypertension) have been reported, with some cases requiring hospitalization; closely monitor patients with cardiac and pulmonary conditions; decrease the infusion rate or discontinue the infusion if necessary

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Drug summary - MICROMEDEX® 2.0 Page 2of;9

• final sterility test results of product may not be available prior to sipuleucel-T infusion; microbial contamination may be reported after infusion ill

• health care professionals; risk of exposure to transmissible infectious diseases present in leukapheresis material; use proper precautions when handling the product ill

• report suspected adverse reactions to the Dendreon Corporation at 1-877-336-3736 or the US Food and Drug Administration at 1-800-FDA·1088 or www.fda.gov/medwatch

• Fetal risk cannot be ruled out,(TH)

View Detailed information in DRUGDEX

• Gastrointestinal: Nausea (21.5% ), Vomiting (13.3% )

• Hematologic: Anemia (12.5% )

• Musculoskeletal: Backache (29.6% )

• Neurologic: Headache (18.1 % )

• Other: Adverse reaction to drug or medicament administered by infusion, All grades (71.2% ), Citrate adverse reaction (14.8%), Fatigue (41.1%), Fever (31.3%), Pain (12.3%), Rigor (59.8% ), Shivering (53.1 % )

• Hematologic: Eosinophilia

• Musculoskeletal: Myasthenia graviS, Myositis, Rhabdomyolysis

• Neurologic: Cerebrovascular aCcident(3.5% )

• Other: Adverse reaction to drug or medicament administered by infusion, Grade 3 (3.5% ), Tumor flare .

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! ,

D~ug summary - MICROMEDEX® 2.0 Page 3 of 9

Common Solutions D5W (D5W-Dextrose 5%) Not Tested II D10W (Dextrose 10%) Not Tested

D5LR (Dextrose 5% in lactated Ringers) Not Tested

D5NS (Dextrose 5% in sodium chloride 0.9%) Not Tested II, D5W - 1/2 NS (Dextrose 5% in sodium chloride 0.45%) Not Tested

NS (Normal saline- Sodium chloride 0.9%) Not Tested .. 1/2 NS (Sodium chloride 0.45%) • Not Tested

Other Solutions

No other drug-solution combinations have been tested.

"Not Tested"

"Not Tested"

II Not

CompatibleIV Il1compati~leIV TestedIVCaution:VariableCaution: UncertainIV

compatibility compatibility compatibility

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Drug summary - MICROMEDEX® 2.0

is is IV compatibility is compatibility is not compatible . incompatible. variable. is uncertain. tested.

• Provenge

.RX

Mechanism

View Detailed information in DRUGDEX

• Sipuleucel-T is autologous cellular immunotherapy that includes antigen presenting cells (APC) that have been activated by a recombinant human protein consisting of prostatic acid phosphatase (PAP; an antigen expressed in prostate cancer tissue) linked with granulocytemacrophage colony-stimulating factor (PAP-CM-CSF). Peripheral blood mononuclear cells are obtained by leukapheresis then during ex vivo culture PAP-GM-CSF binds to the APes and is processed into smaller protein fragments that are displayed on the surface of the APe. Although the exact mechanism of action of sipuleucel-T is unknown, the therapy is thought to induce an immune response against PAP

\

General·lnformation • use proper procedures for handling and disposal of leukapheresis materials and sipuleucel

-T ill Intravenous • after removing from the insulated container, use within 3 hr at room temperature

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D~Jlg summary - MICROMEDEX® 2.0 Page 5 of9

• manually mix infusion bag contents (slightly cloudy with cream-to-pink color) gently and disperse small clumps of cellular material; do not administer if clumps remain after mixing

• consult cell product disposition form and product label prior to infusion; do not initiate infusion of expired sipuleucel-Till

• administer entire contents of infusion bag IV over 60 min; do not use a cell filter

Yiew Detailect informaJion in DRUGDEX

• acute infusion reactions; in patients with cardiac or pulmonary conditions ill

C.U:N;U;:AL%';~Cij,lNG.·,....... . . .. ........'•.• '.','\:.,:/. :"<:::·ijj,::" ':-,;W;;:"·f ,:.' h,'::)Y':.,:_"='!~~%=";:;~~AC'=-~~__-"","~~~,,--,-

• Drug may cause chills, fatigue, fever, back pain, headache, joint ache, and nausea. ill

• Instruct patient to report signs or symptoms of an infusion reaction (may occur within 24 hours of infusion), tachycardia, or cardiac arrhythmias. ill

Sipuleucel-T (Intravenous route, Suspension)

1. Product Information: PROVENGE(R) suspension for IV infusion, sipuleucel-T suspension for IV infusion. Dendreon Corporation, Seattle, WA, 2010.

Strength of Recommendation Class I - Recommended

• The given test or treatment has been proven to be useful, and should be performed or administered.

Class IIa - Recommended, In Most Cases

• The given test, or treatment is generally considered to be useful, and is indicated in most cases.,

Class lIb - Recommended, In Some Cases

• The given test, or treatment may be useful, and is indicated in some, but not most, cases.

Class III - Not Recommended

• The given test, or treatment is not us~ful, and should be avoided.

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Drug summary - MICROMEDEX® 2.0 Page 6 of;? ~

Class Indeterminate - Evidence Inconclusive

Strength of Evidence Category A

iI Category A evidence is based on data derived from: Meta-analyses of randomized controlled trials with homogeneity with regard to the directions and degrees of results between individual studies. Multiple, well-done randomized clinical trials involving large numbers of patients.

Category B

• Category B evidence is based on data derived from: Meta-analyses of randomized controlled trials with conflicting conclusions with regard to the directions and degrees of results between individual studies. Randomized controlled trials that involved small numbers of patients or had significant methodological flaws (e.g., bias, drop-out rate, flawed analysis, etc.). Nonrandomized studies (e.g., cohort studies, case-control studies, observational studies).

Category C

• Category C evidence is based on data derived from: Expert opinion or consensus, case reports or case series.

No Evidence

FDA Pregnancy Ratings Rating A

• Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.

Rating B

• Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown adverse effect (other than a decrease in fertility) that was not confirmed in ,controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Rating C

• Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Rating D

• There is positiv(2 evidence of human fetal risk, but the benefits' from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

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". ~1ug summary - MICROMEDEX® 2.0 Page 7 of9

Rating X

/. Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Australian (AUS) Pregnancy Ratings Rating A

• Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

Rating 81

• Drugs which have been taken by only a limited number of pregnant women and women of childb!=aring age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

Rating 82

• Drugs which have been taken by only a limited number of pregnant women and women of childbearing agel without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

Rating 83

., Drugs which have been taken by only a limited number of pregnant women and women of . childbearing agel without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Rating C

• Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

Rating 0

• Drugs which have caused{ are suspected to have caused, or may be expected to cause an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

Rating X

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Drug summary - MICROMEDEX® 2.0 Page 8 of 9 1.)

• Drugs that have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy.

Thomson Pregnancy Ratings Rating Fetal risk cannot be ruled out.

• Available evidence is inconclusive or is inadequate for determining fetal risk when used in pregnant women or women of childbearing potential. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during pregnancy.

Rating Fetal risk has been demonstrated.

• Evidence has demonstrated fetal abnormalities or risks when used during pregnancy or in women of childbearing potential. An alternative to this drug should be prescribed during pregnancy or in women of childbearing potential.

Rating Fetal risk is minimal.

• The weight of an adequate body of evidence suggests this drug poses minimal risk when used in pregnant women or women of childbearing potential.

AAP Lactation Ratings Cytotoxic drugs that may interfere with cellular metabolism of the nursing infant.

Drugs for which the effect on nursing infants is unknown but may be of concern.

Drugs of abuse for which adverse effects on the infant during breastfeeding have been reported.

Drugs that have been associated with significant effects on some nursing infants and should be given to nursing mothers with caution.

Maternal medication usually compatible with breastfeeding.

Radioactive compounds that require temporary cessation of breastfeeding.

WHO Lactation Ratings Avoid breastfeeding.

Avoid breastfeeding if possible. May inhibit lactation.

Avoid breastfeeding if possible. Monitor infant for side effects.

Compatible with breastfeeding.

Compatible with breastfeeding. Monitor infant for side effects.

WHO documentation states insufficient data.

Thomson· Lactation Ratings Infant risk cannot be ruled out.

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D§ug summary - MICROMEDEX® 2.0 Page 90f9

• Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.

Infant risk has been demonstrated.

• Evidence and/or expert consensus has demonstrated harmful infant effects when used during breastfeeding. An alternative to this drug should be prescribed or patients should be advised to discontinue breastfeeding.

Infant risk is minimal.

• The weight of an adequate body of evidence and/or expert consensus suggests this drug poses minimal risk to the infant ~hen used during breastfeeding.

Milk effects are possible.

• Evidence suggests this drug may alter milk production or composition. If an alternative to this drug is not prescribed, monitor the infant for adverse effects and/or adequate milk intake.

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CP - Sipuleucel~T - Description / Classification Page 1 of 1

,- .- ., - "'. ,,'/

Sipuleucel-T (Provenge or APC-~015). is an autolo~ouS cellul,! r .imm~.~oth~rapyuse.df~r. tht!yeati)1~~rofp:r9St~J~.tanc~i. Tn\,va~~ine.is. <;.omp?~.edqf aul,ol,og()uS peripheral blood mononuclear cells, including antigen p~esenting CeUS!(A~'t~), 'c/~'~lJre~!\!vithY~,r4sij)~'prQl~in, S~~cifii:aiIY, sip~leu~ei'+I;prociu~edby dendritic cell precursors to a recombinant fusion protein (PA2024);~~iCh.iS."'~d" Up.~fJ)rOs;atic~ci~Ph?S"hiltaSe{PAP) fusedt7granUIQCyte-ma~rOPhage colony-stimulating factor (PAP-GM -CSf). The patient's peripheral bIO:i:i.dJl101pnudears~fls~t~.;9bta'~edVi.a.standardle~kaPheresiSiapprP"imat~IY 3 days pridr the sipuleucel- T infusion date. The potency of sipuleucel- T is determined in par'; by meaSlJri~gthe inc:reased· expres'Sio~ of the C054 molecule on th'; surface of

APCs after culture with PAP-GM-CSF. CD54 is a cell surface moteculethat.P1aydi,·role.;i~'the..;,immunblogi~,;;hteri!ctions.;between AP-CS and;T cell'$, an(jis

considered a marker of immune cell activation. Each dose Of~iPUleucel-TcontainsalTli~iI11UrnOf§()millionautoI090U~C!JS4+ cellsacti~ated'wii:h a phase IlJ trial of 512 patients with meta~taticcastrate'r~sistant Pt~statecance.90V7r<lllsji'iWiyav;.,vas~t~nificiihtly 9rl!ateripp,wents"re:ceilvitIQ compared toplacebo (25.8 months v. 21.7 months, p~ OO~2(I~April~oio,s<ipUleUc~i?r~~~i'.appr?Val'fO~ th~~reatme'nt ".(pa

or min i m a"ysymptor\, a t ie, metastatic, and roge n -Inde pende n t,thor"lOd;e riW"ct0f>V2 p rpSta te;;~l~ciPyl~,~c~ I',! is t~l!;fi rst.~ctiv~'ce It ~ lilt i the first bio!ogicappraved to treat prostate cancer.!40277J ',' ..' .......... 0

Classifications

S' Antineoplastic Agents ,. Biologic Response Modifiers

, . "Active Cellular Immunotherapies

Chemical Structure,

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CP - Sipuleucel-T - Mechanism of Action Page 1 of 1

Mechanism of Action: Sipuleucel-T is an autologous ~eHular 'mmun~ther~ll¥d.,~,!~nedl? sti.n~lal:;{T-te~1~?,mhl!litY ~gainstP[ost,~ii<: a~i9Phq.sBhata,;~ antigen expressed in prostate cancer tissue but not .in non-prostatetissue.[403031Whilethe.exastm'echanismQf-actionisunknown'"it iSdependentl/Po~

effective presentation of this target antigen to the. patient's immunesystem.,Th'e.,,~~tive:om~?~ents,o(sip~leucel-Tare antigen,presenti.n~c~IIS (AP~s) and GM-CSF; [40277J APCs are responsible for the presentation of antigens'to T'~ells,:r402891The ;APCs within 'siPuleu'cel-rare from autologaUsperip~eral.lJlood',

mononuclear celis, which are obtained dUring. a standard leukaPh. eresis. proc ...e.dure .. ...~e ...nt ...o ..,.,pr.o.Xlm alely 3 d.ays p riorta the .• ...n. The.,., ',APCS ..........,t....hat.,..,t .. ·, ..P~~i...e .., '.J,nderg ....".s. ap .. .. ... ,infUSio ' are activated during a culture period with a recombinant humanprate'n, PAP~GM·CSF, which eonsisJs"ofPAP linked to granulocyte-macrophagecolonY'stimulating 1

factor (GM-CSF), an immune cell activator. During the culture processwith PAP.,GM-CSF;APCstakeup'aRd process the recombinant targetantlgeninto small

peptides that are then displayed on the APC surfaCe. I~inimal residuall~vel~,of t~~:int~;ft,PAP;FM-C.S,t, a~~)d~tect,:ble {nthefioal slpule~cel-T product-The recambinanta ntigen is designed to target APCs andmay help direct the im?,u~e r~~po?s:to PAP.,T~epotency ofSipul"u~el T is determined in part by measuring

the increased expression of the CD54moiecuie on the surfaW'9fthei~PCs~{ter~p:lture'!:"ith:e~P-G~f'CSF'''fD5\al.a!know~i,as leAM-I,isa c~!lsurf~ce moleeul that plays a role in Immunologic interactions betweenAPC~ andT:c~IIS,aOdi~.tonsi;l,;;edamarkerO(irnmun~c~eilaetivation: The finalcellulai-2~"1Position of sipuleucel,T is dependent upon the c"lIular compositjonofthel~!Jkapheresis.product. In'addition tj)~!PCsrthe fina.1 producLcontain~.T e~lls; Bic~lls<n,atuial:!'~il1er (NK) cells, and other i:ell.'[402771 ". ... - , . .,v'

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CP - Sipuleucel-T - Pharmacokinetics Page 1 of 1

,>. --.i, __ : -.,;-:', ",.,j:ti:,:.,... ,,,,_,;:':::':>::: ,_::-,,;;'::::'."-'" .. __ .:' ;>:--::-: _ _ _ __' Ph,~rmacok-inetiC-s: Sipuleucel- T is administered by intravenou:;_;infu.:,S_i_on., I,t is a_:_~_~nd~:_~t!~cC~__!I_,prod,:~~t :th~~ ,_~on:Si~_tS'Of_~utOI:og.Ou,s d prostatic-acid phosphatase linked to granulocyte-m~croPh~ge.¢<>IOny,stimul~tl~~JaJtor;£f.?AP"~~-C?n;.I~~';Phaselllcontrolled.cli;;i.cal prostate cancer were evaluated for the development of humoralandTcellimmJn:,response~(.~ronf:rativea"d~amma-interfer"h ELISPo:)t? '. . rget antigens.(at baseline and 'at weeks 6, 14, and 26)'IgG anf' Igl)I.~ntiQOpyre~po~*~.~.ag~idstP.A.~-G':"~,SSF~·ri~.agai.n~tl'~P alpile wereob~~(vedinroughthefd.110'1(: up period. T cell proliferative and gamma-interferon ELISPOTresponses.werepbser~ed i~periPh~ral.bIOOd collected in t~efollow-Upperiod from patients receivingsipuleucel-r: Responses were not observed in the con",ol 9f.P~P' ·~.eJ"e.~jE~leJi:.~I-T;'i!atie'lt~';x~ibitedi'fresq9~se ~O.PAfl)~!)iJg~~':a loq~, Th~cliniS)~1 significance of antibody. responsesis not known.[402pJ Inanothertrial,the specifiCT-celiresponsive~ess ~gai';st)t~e targetantJge9:"a~ determined ina small

group .of pati~nts whose cells were proc~ssellwithin24 hours gtcoll.~F;fion!'the!l'l~lliaQ··t)~tiO)i!f the:,~A20~l\(a rl!~p";l.iini' nt.!g~ion~fotei?Con~.~tni n~ •. ~rostat&c acid· phOSPhatase and )GM-CSf) T-cell stimul~fionindex at8w!",'kS ve.'su, b;,;seli",l, was ,i'pproxil1'lately eight'fpld·higherinsip·~lepce(~T-versus"plac.~~o:vea)ted. patientsJ40289] 'j;;.;.) ,s"; ;};;;; .;"" ;';1, '", ':co . c)'

<.'.:::- ---.:~:<;'>: ------ i'\;,'::'" -- --- ,:,:':.:.:;:' ---- _::;',:':':::,' ..

•',:7VTS l~ffi.Da:~,,;S)5(~:,!Ot~;~l21l~gPMr,

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CP - Sipuleucel-T - Contraindications/Precautions Page 1 of 1

Sipuleucel-T .is intended solely forautolog'ous use.f402ih

Sipuleucel-T is not routinely tested for transmlsSiblelnfectio.u'sdisea!;e;

infectious diSease to. healthca,e professionals hand"~g t~esefj1aterialsy~euniyers.i!t IJr~l\autjf'ps.;

, '-,:' - -" ::- ";-'- ,"" -.,-: " ,::,:.,; , ,::, ~;---, ,-,' \ ,>

Acute infusion-related reactions have occurredduri.ng treatment with. sip~l~uc~H.!pes~J~a~tionsMciuded,b~t w~renotlimitedtP, lever, chills, respiratory ev.ents (dyspnea; hypoxia, and bronchospasm)} nausea;__ ~omitingf: ,fatip~J~/_ hypert~n~i_~,~,.';a_'~~,:,"tac~ycar~l,~'.- U~e_~ ~aut_,ion a-nd ~qn;tor patie~t~, cI,QseIY:,V'jhen ' administeringsipuleucel-T to patients with ca rdiacdisease orpulmoni'ry:{jisea~~. Ir':Elini[jll tripls, ?:t2°/r~f ~.at.ientsdeveJo.ped:an.~cutein,fu~t!ln,related reaction., The majority, of these reactions. (95.1 %) w~_re 'mird' t,_D .l1)o~"~_rat~,:,,irr' _~7,~,~_rit~,:_53r~,~_~"'~:'.:~:~lJt_~:,:~:nf.us~~:."-~r:·1ate~" react:.'?X15 :~~"Cu,~,r~d rn, ,~:. 5°~o.. ,Of :.:~ati~'nt5~"N~.,

4 or grade S infusion reactions were observed .. Inllatien!'!; wMd~yelop~n aq:~tei,ritU~ion}rel'l~E!dr:e~cti,~n,. t~¢:infu§ion'rate m~x~edecr¢as'1di orsto.pP¢<l, depending on the sev.erity of the reaction. Administer. ap.p.. ropria. te medicallherapyas necessary.C402771 "

: .:r,:,:' .\'" >,;.:'( ')!,':,,: ',," :",:,~< ".' :-":'\". :;,:':';:-. ''',

The use of chemotherapy or immunosuppressant agents duringtrea;mentwitl) ~:iPUI:Fucel.:T,Sh()uld~eaVq.id~d:!'(.hen pbssible'<:9ncurrenta.dmi.nistrat!pn Hf immunosuppressant agents with the .Ieukapheresis procedure I\as nolbeen. studied/Sipuje~cer.:TstflTnllat~s. the'immu'n.e 5y5terrrand. patients with.

immunosuppression induced by other medications may have adimi~!sl1e?:.reSPOQSeJ9Sipul:eUC.!1I,T'5pnSi~erqi~conti9uingOr~ed~Cing the do.eof , immunosuppressant agents prior to initiating therapy with'sipuleucel~T,when appro·priate. In addition, sipuleucel·Tis released by the manufacturer/or infusioh

prior to receiving fin~1 sterility test results (7-day incubation). Sipuf~ucel-Tis>r~lea.ed forir1f\!sjOri:base<!~n the following microbiaL and sterility tests: Gram stain, endotoxin content, and in-process sterility with an incubation!;me'6f;2-days todetermin'e the absence. o.f miCrobial growth. If proof of micro.bial

contamination becomes evident after the product has been approvecilorinfusi9~,De:hdr79nw.iu:~ontact.t?etreatin9.physician,Dendreon\Vili also attemptto identify the microorganism, perform antibiotic sensitivity testing on r~covered' micto~r:gani~mS, and '{ommunicate the result. to the treating physician.LiQ1J.l1

Safety and efficacy have not been established in children, infants,·and neOriates;lli.f12J



CP - Sipuleucel-'f - Interactions Page 1 of 1

Concomitantuse ofs ip uleu~el-T . a n d~ntioeoPla~tita~ents\hRZ!d.b~•.avbI9~p" CQ~~uhenJ<l d'hi~l.stra\i9P cif ;lliti rjecllljilstic,ag.l~ lit:s.",~.ith th,LI E~u~,ap,here.';.i s· procedure that occurs pifor tosipuleucel-T infuS;·on has not"ljeenstudied:.·sipUj~~C~I-T:;stf;"ul;tli~ th~"imm {n:·r'f·';v,t":n~: may have a diminished response toslpuleucel-T. When appropriate, cons'iderdisc8ntinuing~r red~~ng the dose of antineopl therapy with s,ipuleucel-T.I40277J " 'j!'"".



CP - Sipuleucel-T - Adverse Reactions Page 1 of 1

Acutei.~fuSion reactions nave occurred. duri 0.9 tr~atTent.with si~gleu5.;1 'T.)?Xi~j:.\esa~.~o~iat~~wit,p ..,fcut~,~~t~si9nre,~,~;ions,.\9y.er::,IITrig~.en9~. pftoxiSitYy-ith sipuleuceloT provided).included·fever (31.3%), chills (53.1ro), :respiratory El~gnts ••(C1ysPIjE!jl·(8;Z!Yo), hyp?xia;an~bmncfjo~pa!;m), I1aqsea(4,l.S~(oLv9jrliting/

(13.3%).. fatigue (41.1 %), hypertension (7.5%),and sinus taChycardi~, Sym~tomsrepO~;ed\"lithi~J d~yO~il1fu5ion 1N~"esonsi~eredpartofan~cuteinfuSion reactio n. Usecaution When adminIstering si puleucel-T to::patier.\s, wit~ Ca rdiitc di~e.~se 9[pU liIr~par'{~iSeare ..10.1)11nlcalJrial~ij L 2"10 of pftient~devel(jped/ap ac.ute infusion rea-etlan. The majority of these reactions (95,;-1%) we,,~_e ~i_I,~}~:,~q,,?e~a~e :j:~;:~~,~_er_~t-~,~' G~_~:d~ ____3a(;ut~ .inf,u:i~n,,:,eactions :?_Ccu~,re~,: i"n J:5% ,,~'f patients, No grade 401 grade 5 infusion reactions were ob~erv,,,d. Inp~tiert1cfwh??eev~'Q:p a~••~j,'uteiNusio.~reaction,Jheinfu.Sionrate m~y be,;(lecreased,qr stopped, depending on the seventy of the reaction. Administer appropriate' ;"edical the;apv as' n'ece;sary;[40277 J . ,

In controlled clinica I trials, cer,ebrovas(ular events, includrng -herr1t)rrhagic"_~f~d -i·sc'h-emk-- sfrO_k'~t 'tic-eu/fed in "l~S'O/O- :6'f patients -receiving sipui'euce'i-l:compare'd to 2.6% of patients receiving placebo.L1Qlll]

Infectious complications during sipuleucel-T treatment included. upper reSpi~~tory.tractinrec:tion (6;3o~~ Ya"durina/y tract infection{[;.5o/~) •. Iil aoditio!), ce~yal venous catheters were required in some patients receiving sipuieuceloT. Iw!;~me of 'the~~ patie~ts, infectiau·s. compJicat;'ons developed, inCludingsepsi·s. ThiS

resulted in discontinuation of treatment in a small number of these patients. Use cauti9n.and ..mOriitorfor iDfectious sequelae in patients with a ce litra I venaus catheter.[4Q277.l

Patients. undergo leukapheresis approximately 3 days prior to.,each infUSion ;.O'fSiPuleuceiiT.ln:€Iinic:ilt,ials',adv~rse eventde:port~d < ~.ldaYfromthe leukapheresis procedureincluded. citrate toxicity (1:;2%),. oralp~reSt;h.~Sia~(F-6.0{q) ,p~.r.esth~~!a;; L~ lAO/O ),.;andJatigu~(8.3%).r4227 7]""

.-z-~-

Musculoskeletal toxi:ities. that occurred duii~gdiri i.~~ltria Is.· Of}iPUI~~.cel;r.in~rGd~.~back, paj? (29.6~/q)(j,?i~tac~el~rth'illgiafi9.6%)'P~inCl~.},oldLPain in extremity (12.; 1%),muscleache/myalgia( 11:8%), . muscle F.ra~ll§. (5 Ii~~ms}:H·70,t,), bO~'tpai 9<~.3'1',o,mU~culosK~jet~·!ph~st;pain (~!'Io) ,)andn~C~pajV,( 5.7W)· (40277) .,

Gastrointestinal toxicities reported during clinical tria1s of SiP~(~u'~-e}-+;i:n'CJ-Ud~d:ri:~:~csea anorexia (6.5%).[402771

Other toxicities that occurred commonly (> = 5%) in patients re(lei'/in\l ..!;ipIU.!~.ucel}·Fi.rlc.U!,'ical.tl'ials.inclludled. (11.8%), asthenia (11l.8%), influenza-like illnes~ (9.7%), p

insomnia (6.2%), cough (5.8%), weight loss (5.7%l,rash (Uils~l.ecifi~,d)

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.. CP - Sipuleucel-T - How Supplied Page 1 of 1

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CP - Sipuleucel~T - Monitoring Parameters Page 1 of 1

,. ,"laborat9.tY monitoring not neces_sa-ry

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.J Clinical Pharmacology Page.1 of 3

Sipuleucel ...T Suspension for injection·

Trade Names

Provenge

The list of names may not include all products that are available on the market.

What is this medicine? SIPULEUCEL-T is a vaccine for the treatment·of prostate cancer. It is made from cells in your

immune system.

This medicine may be used for other purposes; ask your. health care provider or pharmacist if you

have questions.

What should I tell my health care provider before I take this medicine? They need to know if you have any of these conditions:

• heart disease

• lung or breathing disease, like asthma • an unusual or allergic reaction to sipuleucel-T, other medicines, foods, dyes, or

p rese rvatives

• pregnant or trying to get pregnant

• breast-feeding

How should I use this medicine? This medicine is for infusion into a vein. It is given by a health care professional in a hospital or

clinic setting. This medicine is made from your own immune cells. Your cells will be collected at a cell collection center approximately 3 days before each infusion of this medicine. Your collected

cells are then sent to a special center where they are mixed with a protein to get them ready for

your infusion,

Talk to your pediatrician regarding the use of this medicine in children. Special care may be

needed.

Overdosage: If you think you've taken too much of this medicine contact a pOison control center

or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose? It is important not to miss your dose. Call your doctor or health care professional if you are

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Clinical Pharmacology Page 2 of 3

unable to keep an appointment. If you miss an appointment for your infusion of this medicine,

your dose will not be able to be used.

What mayint~ract with this medicine?

• medicines that suppress your immune system like some medicines for cancer

• steroid medicines like prednisone or cortisone

This list may not describe all possible interactions. Give~ your health care provider a list of all the

medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you

smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What side effects may I notice from receiving this medicine? Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue

• breathing problems

• chest pain or palpitations

• dizziness • fast,irregular heartbeat

• fever • nausea, vomiting

Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):

• back pain

• fatigue

• headache • joint pain

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-SOO-FDA-10SS.

What should I watch for while using this medicine? Report any side effects that you notice during your treatment right away, such as changes in your breathing, fever, or chills. These may also occur after your infusion.

Tell your doctor or health care professional if you have any other reaction or unusual symptom after getting this medicine.

Where should I keep my medicine? This drug is only given in a hospital or clinic and will not be stored at home.

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! Clinical Pharmacology Page 3 of 3

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

[Last revised: 05/03/2010]

Copyright ©2011 Gold Standard

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\ .... Obtained by Judicial Watch, Inc. via FOIA

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I I i I I

!,I I

Intravenous Administration

• Sipuleucel-T is intended solely for autologous use. Confirm the proper product has been received according to the label onthe outside of the insulated polyurethane

container. Prior to infusion, match the patient's identity with patient identifiers on the Cell Product Disposition Form and the sipuleucel-T infusion bag.

• : Premedication with acetaminophen and an antihistamine such as diphenhydramine should be given approximately 30 minutes before each infusion to attenuate infusion

related events. • Patients require close monitoring during the infusion due to the potential for severe

pulmonary and cardiovascular infusion-related reactions. • Storage: Sipuleucel-T infusion bag must remain in the insulated polyurethane

container arid inside the outer cardboard shipping box until the time of administration. [40277]

Preparation for infusion:

• Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF, suspended in 250 ml Lactated Ringer's Solution, USP in

a sealed, patient-specific infusion bag. • Remove the bag from the insulated polyurethane container and inspect the bag for

leaks. Do not administer if the bag leaks. • Contents of the bag will be slight~y cloudy with a cream-to-pink color. Gently mix to


';

re-suspend the contents of the bag, inspecting for clumps and clots. Small clumps of cellular material should disperse with gentle manuaL mixing. Do not administer if the

bag leaks during handling or if clumps remain in the bag.[ 40277]

Intermittent infusion:

• Infusion must begin prior to the expiration date and time indicated on the Cell Product Disposition Form and Product LabeL Do not initiate infusion of expired sipuleucel-T.

Sipuleucel-T is supplied in a sealed, patient-specific infusion bag. • Infuse the entire volume in the infusion bag over approximately 60 minutes. Do not

use a cell filter. • Observe the patient for at least 30 minutes after the infusion is complete.

• If an acute infusion reaction occurs, the infusion may be interrupted or slowed, depending on the severity of the reaction. In clinical trials, acute infusion reactions

. were treated with acetaminophen, intravenous HI and/or H2 blockers, and low dose meperidine. If the infusion must be.interrupted, do not resume if the sipuleucel-T is at

room temperature for more than 3 hours.[40277]

!
