Jo-Ann Ford, RN, MSN Associate Director BC Hepatitis Program Diamond Centre, VGH Advances in HCV Treatment - Where Are we Going? Where Are we Going?

Jo-Ann Ford, RN, MSNJo-Ann Ford, RN, MSNAssociate DirectorAssociate DirectorBC Hepatitis ProgramBC Hepatitis ProgramDiamond Centre, VGHDiamond Centre, VGH

Advances in HCV Treatment -Advances in HCV Treatment - Where Are we Going?Where Are we Going?

Disclosures – J. FordDisclosures – J. Ford

• Clinical Trials:

– Hoffmann LaRoche, Merck Canada, Vertex Inc., Pfizer Canada, Johnson & Johnson, Gilead Sciences, Human Genome Sciences, Boehringer Ingelheim

• Advisory Boards:

– Merck Canada, Hoffmann LaRoche, Gilead Sciences, Vertex Inc.

IntroductionIntroduction

• Prevalence HCV in Canada: 1-2%

• BC: Estimated 60,000 – 100,000 chronic carriers

• HCV in Canada

– Yesterday: recipients of blood transfusions

– Today: horizontal transmission (IVDU)

U.S.A. 4 M

SOUTH

AMERICA

10 M

AFRICA 32 M

EAST MEDITERRANEAN

20M

SOUTH EAST ASIA30 M

AUSTRALIA0.2 M

SOURCE, WHO

WEST EUROPE

9 M

FAR EAST ASIA60 M

170 Million Carriers Worldwide

3% of World Population

HCV: A Global Health Problem

CANADA 300,000

Hepatitis C Disease Progression

Acute Infection Chronic Infection Cirrhosis Death

5% of chronic HCV-infected cirrhotic individuals per year

Liver Failure (Decompensation)

10-20% of chronic HCV-infected individuals

• 80% of infected patients progress to chronic disease

• acute infection often silent

Approx 20% of patients decompensate within 5 years of developing cirrhosis

Liver Cancer (HCC)

Chronic HCV is the leading cause of liver transplantation in the US and Canada

Liver Transplantation

Goals of TreatmentGoals of Treatment

• Cure HCV infection

• Suppress disease activity

• Halt or reverse fibrosis progression

• Reduce risk of hepatocellular carcinoma

• Control extrahepatic consequences of HCV infection

Hadziyannis. J Eur Acad Dermatol Venereol. 1998.

HCV Infection: Extrahepatic Manifestations

Haematological• Mixed cryoglobulinemia• Aplastic anaemia• Thrombocytopenia• Non-Hodgkin’s -cell lymphoma

Dermatological• Porphyria cutanea tarda• Lichen planus• Cutaneous necrotising

vasculitis

Renal• Glomerulonephritis• Nephrotic syndrome

Endocrine• Anti-thyroid antibodies• Diabetes mellitus

Salivary• Sialadenitis

Ocular• Corneal ulcer• Uveitis

Vascular• Necrotising vasculitis• Polyarteritis nodosa• Pulmonary fibrosis

Neuromuscular• Weakness/myalgia• Peripheral neuropathy• Arthritis/arthralgia

AutoimmunePhenomena• CREST syndrome• Granuloma• Autoantibodies

88

Increasing proportion of liver transplantations due to HCV

0100 02

6.56.5

4646

%

Year

UNOSUNOS

% o

f liv

er tr

ansp

lant

due

to H

epat

itis

C%

of l

iver

tran

spla

nt d

ue to

Hep

atiti

s C

90 91 92 93 94 95 96 97 98 990

10

20

30

40

50

60

Source: UNOSSource: UNOS

Current HCV Therapy: 2010Genotype 1 in need of better therapies

2%9%

17%

29%

38-41%

0%

20%

40%

60%

80%

Sus

tain

ed R

espo

nse

IFN 24w IFN 48w IFN-R 24w IFN-R 48w PEG-R

HCV hepatitis C virus; IFN interferon

Late 1980’s 2010

IDEALPeginterferon Alfa-2b

or Alfa-2a with Ribavirin forTreatment of Hepatitis C Infection

McHutchison J et al.

N Engl J Med 2009; 361:580-93.

Study Schema and Treatment Regimens

N = 1019 PEG-IFN alfa-2b 1.5 μg/kg/wk

+ RBV 800-1400 mg/d× 48 weeks


+ RBV 800-1400 mg/d× 48 weeks

N = 1035PEG-IFN alfa-2a 180 μg/wk

+ RBV 1000-1200 mg/d× 48 weeks

N = 1035PEG-IFN alfa-2a 180 μg/wk

+ RBV 1000-1200 mg/d× 48 weeks


+ RBV 800-1400 mg/d× 48 weeks


+ RBV 800-1400 mg/d× 48 weeks

ScreeningScreening

Follow-up24 weeksFollow-up24 weeks



2 4 12 24 48 4 12 24

Stratified by baseline viral load (> or ≤ 600,000 IU/mL) and race (African American)Stratified by baseline viral load (> or ≤ 600,000 IU/mL) and race (African American) Standard response stop criteria applied at weeks 12 (no EVR) and 24 (HCV RNA-positive) Standard response stop criteria applied at weeks 12 (no EVR) and 24 (HCV RNA-positive)

HCV RNAa

a LLQ <27 IU/mL (COBAS TaqMan; RocheLLQ <27 IU/mL (COBAS TaqMan; Roche))

Treatment Discontinuation:Non-Response

• Week 12– Subjects with TW12 HCV RNA decline < 2 log10 were

discontinued – Subjects with TW12 HCV RNA decline >2 log10 but not

aviremic were continued on therapy and re-assessed at treatment week 24

• Week 24– Subjects who did not achieve aviremia by TW 24 were

discontinued

• Note: similar to current community practice!

Screening, Treatment, and Follow-up

4469 patients screened

3083 met inclusion criteriaand randomised

1654 completed treatment:540 standard-dose PEG-IFN alfa-2b + RBV

493 low-dose PEG-IFN alfa-2b + RBV621 PEG-IFN alfa-2a + RBV

13 randomised but not treated

1416 discontinued treatment: 830 had treatment failure, 362 had adverse event, 224 had other reason;Of these, 383 never entered follow-up

2417 completed follow-up:812 standard-dose PEG-IFN alfa-2b + RBV


1386 excluded due to:Ineligible for protocol, declined, lost to follow-up, noncompliant, adverse event

3070 treated:1019 standard-dose PEG-IFN alfa-2b + RBV


SVR Similar Across Treatment Regimens

0

20

40

60

80

38%

41%

% o

f P

atie

nts

Wit

hU

nd

etec

tab

le H

CV

RN

A

PEG 2b 1.0 /R(n=1016)

PEG 2a /R(n=1035)

40%

PEG 2b 1.5 /R(n=1019)

1.5/RBV PEG-IFN alfa-2b vs. PEG-IFN alfa-2a 180/RBV, P=0.57

PEG-IFN alfa-2b 1.5/RBV vs. PEG-IFN alfa-2b 1.0/RBV, P= 0.20

Advances in Therapy

No treatmentNo treatment

IFNIFN(6 months(6 months))

IFNIFN(12 months(12 months))

IFN+IFN+ribavirinribavirin

(12 months(12 months))PeginterferonPeginterferon(12 months(12 months))

Peginterferon Peginterferon ribavirinribavirin

STAT-CSTAT-C

??

19911991 19981998 20002000

100%100%

50%50%

SustainedSustainedvirologicvirologicresponseresponse

raterate

Phase IPhase I

Phase IIPhase II

Phase IIIPhase IIIOthersOthers

Non-Nuc Polymerase inhibitors

Non-Nuc Polymerase inhibitors

Nuc-Polymerase inhibitors

Nuc-Polymerase inhibitors

NS5A inhibitors inhibitors

NS5A inhibitors inhibitors

Protease inhibitorsProtease inhibitors

HCV Pipeline* by MOA and Stage of Development

3/2/2010 – selected compounds only

PreclinicalPreclinical

Telaprevir (J&J/Vertex)

Boceprevir(MRK)

MK7009(MRK)

MK5172(Merck)

GS9256(Gilead)

BMS650032 (BMS)

ITMN-191/R7227 (Roche/Intermune)

TMC-435 (J&J/Tibotec)

BI201335 (BI)

ABT450 (ABT) ACH1625 (Achillion)

GS9190(Gilead)

ANA598(Anadys) VX22

(Vertex)

filibuvir(PFE)

IDX375(Idenix/NVS)

ABT333. ABT072(ABT)

BI201127 (BI)

BMS-791325 (nuc or non-nuc)(BMS)

INX189(Inhibitex)

Biocryst

PSI938(Pharmasset)

GL59393 (GSK)

Medivir/Tibotec

R0622 (Roche)

BI

Japan

Tobacco

IDX-184 (Idenix)

PSI-7977(Pharmasset)

R7128 (Roche/Pharmasset)

Vertex

Enanta

PresidioGSK

Idenix

Merck

AZD7259 NS5A (AZN)

BMS790052 NS5A (BMS)

BMS824393 NS5A (BMS)

Taribavirin (Valeant)

Caspase inhib (Gilead)

Nitazoxanide(Romark)

Debio025 and NIM811 cyclophilins (Novartis)

INF lambda (Zymogen/ NovoNordisk)

Roche

BMSVertex

Gilead

STAT-C Combinations

FiledFiledALBUFERON

(HGS/Novartis)

*Publicly available information via press release, corporate presentations and assumptions based on patent filings

What will be the

Standard of Care for

Genotype 1 Patients?

24 wks Follow-up

HCV SPRINT-2 – Boceprevir + PegIntron® + RBV in Naïve G1 –

Phase III

Randomization (1:1:1, stratified by G1 subtype and BL VL)

Study Weeks 480 72

CH

C,

G1,

naï

ve,

n=

1097

(in

cl.

159

AA

) PegIntron® 1.5 µg/kg/wk plus RBV 600-1400 mg/d plus placebo (starting at study week 5)

PegIntron® 1.5 µg plus RBV 600-1400 mg/d plus

boceprevir 800 mg tid

PegIntron® 1.5 µg plus RBV 600-1400 mg plus boceprevir 800 mg tid

284

* Pts in the 28-wk-arm who are HCV RNA undetectable at week 4 of boceprevir tx (=study week 8) and all subsequent assays will stop tx at wk 28Pts who are not undetectable will stop boceprevir at week 28 and will continue with PegIntron® plus RBV alone for an additional 20 weeks

PegIntron plus RBV

PegIntron plus RBV

8 *

24 wks Follow-up

24 wks Follow-up

PegIntron® plus RBV plus placebo

44 wks Follow-up

Poordad et al, AASLD 2010, oral (LB-4), Bronowicki et al, AASLD 2010, poster (LB-15)

SPRINT-2 – SVR (ITT)

* *

* p<0.0001Per protocol, if a pt did not have a 24-week post-tx assessment, the patient’s 12-week post-tx assessment was utilizedPress release, August 4, 2010

SPRINT-2: SVR Rates in Patients Who Qualified For 28 Weeks of Therapy

44% of patients qualified for 28 weeks of therapy (assessment at Week 4 of BOC, ie Week 8 of therapy) in response-guided arm

0

20

40

60

80

100

Non-blacks

SV

R (

%)

Blacks

8797

n/N = 143/147 13/15

SPRINT-2: SVR and Relapse Rates (ITT)

0

20

40

60

80

100

Pat

ien

ts (

%)

SVR Relapse

4-wk PR + 44 weeks BOC/PR4-wk PR + response-guided BOC/PR 48-wk PR

67 68

40

8

23

9

0

20

40

60

80

100

Pat

ien

ts (

%)

SVR Relapse

42

53

2317 1412

Nonblack Patients Black Patients

P < .0001P = .044

P = .004

Poordad F, et al. AASLD 2010. Abstract LB-4

n = 211 213 125 21 18 37 22 29 12 3 6 2

SPRINT-2 – Discontinuation due to Adverse Events

Poordad et al, AASLD 2010, oral (LB-4)

Boceprevir: Adverse Events

1. Poordad F, et al. AASLD 2010. Abstract LB-4.

• Anemia and dysgeusia reported more frequently in BOC arms vs control in SPRINT-2

Outcome 4-Wk PR + Response-Guided

BOC/PR(n = 368)

4-Wk PR + 44-Wk BOC/PR

(n = 366)

48-Wk PR (n = 363)

Adverse event, %

• Anemia[1] 49 49 29

• EPO use 41 46 21

• Dysgeusia[2] 37 43 18

• Anemia discont. 2 2 1

Ira M. Jacobson, John G. McHutchison, Geoffrey M. Dusheiko, Adrian M. Di Bisceglie, Rajender Reddy, Natalie H. Bzowej,

Patrick Marcellin, Andrew J. Muir, Leif Bengtsson, Ann Marie Dunne, Nathalie Adda, Shelley George, Robert S. Kauffman

and Stefan Zeuzem

Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin in

Genotype 1 HCV Treatment-Naïve patients:

Final Results of Phase 3 ADVANCE Study

ADVANCE: Study Design

(T) TVR = telaprevir 750 mg q8h; Pbo = Placebo; (P) Peg-IFN = pegylated interferon alfa-2a (40 kD) 180 µg/wk; (R) RBV = ribavirin 1,000 or 1,200 mg/dayRoche Taqman® v2 LLOQ of 25 IU/mL

(T) TVR = telaprevir 750 mg q8h; Pbo = Placebo; (P) Peg-IFN = pegylated interferon alfa-2a (40 kD) 180 µg/wk; (R) RBV = ribavirin 1,000 or 1,200 mg/dayRoche Taqman® v2 LLOQ of 25 IU/mL

eRVR = HCV RNA undetectable at week 4 and week 12, Response-guided therapy

240 48 72Weeks 128 36

Follow-upPR48

(control)

SVRPbo + PR PR

T12PR TVR + PR

Follow-upSVR

eRVR- PR .

eRVR +eRVR +Follow-up

SVR

PR

Follow-upSVR

TVR + PR

T8PR

eRVR- PR .

Pbo +

PR

Follow-upSVReRVR +eRVR +

PR

72 weeks72 weeks

Follow-up

Follow-up

Randomized, Double-Blind, Placebo-Controlled for TVR

Presented at AASLD – November 2, 2010Presented at AASLD – November 2, 2010

Demographics and Baseline Characteristics

T12PRN = 363

T8PRN = 364

PRN = 361

Gender, n (%)Male 214 (59) 211 (58) 211 (58)

Race†, n(%) Caucasian Black/African American

325 (90)26 (7)

315 (87)40 (11)

318 (88)28 (8)

Ethnicity, n (%) Hispanic/Latino 35 (10) 44 (12) 38 (11)

Age, median years (range) 49 (19-69) 49 (19-68) 49 (18-69)

BMI, median kg/m2 (range) 26 (18-47) 26 (17-46) 26 (17-48)

HCV RNA ≥ 800,000 IU/mL*, n (%) 281 (77) 279 (77) 279 (77)

HCV Genotype Subtype**, n (%) 1a 1b 1, unknown

213 (59)149 (41)1 (<1)

210 (58)151 (41)

3 (1)

208 (58)151 (42)

2 (1)

Stage of fibrosis or cirrhosis, n (%) Bridging Fibrosis Cirrhosis

52 (14)21 (6)

59 (16)26 (7)

52 (14)21 (6)

†Race and ethnicity were self-reported *Roche Taqman® v2 LLOQ of 25 IU/mL**5’NC InnoLipa assay Presented at AASLD – November 2, 2010Presented at AASLD – November 2, 2010

SVR rates in Telaprevir-Treated Patients Compared to Peginterferon/Ribavirin Alone

SVRSVR

75756969

4444

P<0.0001

P<0.0001

271/363271/363 250/364250/364 158/361158/361n/N =n/N =

Per

cen

t o

f p

atie

nts

wit

h S

VR

Per

cen

t o

f p

atie

nts

wit

h S

VR

0

10

20

30

40

50

60

70

80

90

100

T12PRT12PR T8PRT8PR PRPR


Undetectable HCV RNA at Week 4 (RVR) and Weeks 4 and 12 (eRVR)

246/363246/363 242/364242/364 34/36134/361 29/36129/361207/364207/364212/363212/363

6868 6666

99

5858 5757

88

Per

cen

t o

f p

atie

nts

wit

h

HC

V R

NA

un

det

ecta

ble

Per

cen

t o

f p

atie

nts

wit

h

HC

V R

NA

un

det

ecta

ble

Week 4 (RVR)Week 4 (RVR) Weeks 4 and 12 (eRVR)Weeks 4 and 12 (eRVR)

n/N =n/N =

0

10

20

30

40

50

60

70

80

90

100

Patients eligible to receive 24 weeks of total treatment



SVR Rates by eRVR Status

189/212189/212 171/207171/207 28/2928/29 130/332130/33279/15779/15782/15182/151

89898383

9797

54545050

3939

eRVR+eRVR+ eRVR- eRVR-

n/N =n/N =

Per

cen

t o

f p

atie

nts

w

ith

SV

RP

erce

nt

of

pat

ien

ts

wit

h S

VR

0

10

20

30

40

50

60

70

80

90

100

48-week regimen 24-week regimen



ADVANCE AEs leading to DC and most common AEs

% Pts. with T12PR T8PR PR

Any AE 99 99 98

Fatigue 57 58 57

Pruritus 50 45 36

Headache 41 43 39

Nausea 43 40 31

Rash 37 35 24

Anemia 37 39 19

Insomnia 32 32 31

Diarrhea 28 32 22

Flu-like symptoms

28 29 28

Pyrexia 26 30 24

Events occurring >10% in any TVR group vs. Placebo are shaded.

ADVANCE – Discontinuation of Treatment due to Rash and Anemia

Jacobson et al, AASLD 2010, oral (211)

What will be the

Approach for

PegIFN and Ribavirin Failures?

Virologic Response Patterns with Peg-IFN/RBV: Treatment Failure

Detection limit

Relapse

Null response

Partial response

Treatment

No

n-resp

on

se

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72

HC

V R

NA

lev

el

Weeks

34Adapted from Shiffman ML. Curr Gastroenterol Rep 2006;8:46–52

2 log10 drop

HCV RESPOND-2 Final Results High Sustained Virologic Response Among Genotype 1

Previous Non-Responders and Relapsers to Peginterferon/Ribavirin when Re-Treated with Boceprevir

Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin

Bruce R. Bacon, Stuart C. Gordon, Eric Lawitz, Patrick Marcellin, John M. Vierling, Stefan Zeuzem, Fred Poordad, Navdeep Boparai, Margaret Burroughs, Clifford A. Brass,

Janice K. Albrecht, and Rafael Esteban

For the RESPOND-2 Investigators

RESPOND-2: Study ObjectivesRESPOND-2: Study Objectives

• Compare safety/efficacy of two treatment strategies with boceprevir added to peginterferon/ribavirin (PR) versus PR alone in genotype 1 patients who failed treatment with PR

• Evaluate safety/efficacy independently in two patient populations, history PR non-responders (decrease of HCV-RNA ≥2-log by week 12 of prior therapy but with detectable HCV-RNA throughout the course of therapy) and relapsers

• Explore response-guided therapy (RGT) vs. 44 weeks of therapy with boceprevir regimen (BOC/PR48)

Week 4

Week 48

PR + Placebo Follow-up

PRlead-in

PR + Boceprevir

PRlead-in

Week 36 Week 72

TW 8 HCV-RNA Undetectable

TW 8 HCV-RNA Detectable/

TW 12 Undetectable

PR + placebo Follow-up

Follow-up

Study Arms and Dosing Regimen

Control48 P/R N = 80

BOCRGT

N = 162

Peginterferon (P) administered subcutaneously at 1.5 μg/kg once weekly, plus Ribavirin (R) using weight based dosing of 600-1400 mg/day in a divided daily doseBoceprevir dose of 800 mg thrice daily

PR + BoceprevirPRlead-in

Follow-upBOC/PR48

N = 161

HCV-RNA measured by the Cobas TaqMan assay (Roche). Patients with detectable HCV-RNA (LLD=9.3 IU/mL) at week 12 were considered treatment failures.

Week 12 futility

RESPOND-2: SVR Rates According to Treatment Arm and Prior Response

0

20

40

60

80

100

Overall

SV

R (

%)[1

]

4-wk PR + 44-wk BOC + PR (n = 161)

59*

PriorNonresponders

PriorRelapsers

48-wk PR (n = 80)

4-wk PR + response-guided BOC + PR (n = 162)

67

21

40

52

7

75

29

69

P < .0001 vs control

(both arms)

1. Bacon BR, et al. AASLD 2010. Abstract 216. These data are available in unpresented abstract format only and will be presented in full during the AASLD meeting. We encourage you to review the presented data before making conclusions.2. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.

*46% of patients inresponse-guided arm eligible for shorter duration of therapy, with 86% SVR rate.[2]

Telaprevir-based Therapy in Genotype 1 Hepatitis C Virus-infected Patients with

Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin:

REALIZE Trial Final ResultsGraham R Foster,1 Stefan Zeuzem,2 Pietro Andreone,3 Stanislas Pol,4 Eric Lawitz,5 Moises Diago,6 Stuart Roberts,7 Roberto Focaccia,8 Zobair Younossi,9 Andrzej Horban,10 Rolf Van Heeswijk,11 Sandra De Meyer,11 Don Luo,12 Gaston Picchio,12 Maria Beumont11

1Queen Mary University of London, Institute of Cell and Molecular Science, London, UK; 2Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 3Università di Bologna, Bologna, Italy; 4Université Paris Descartes, INSERM Unité 567, and Assistance Publique–Hôpitaux de Paris, Cochin Hospital Paris, France; 5Alamo Medical Research, San Antonio, TX, USA; 6Hospital General de Valencia, Valencia, Spain; 7Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; 8Emilio Ribas Infectious Diseases Institute, São Paulo, Brazil; 9Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA,USA; 10Medical University of Warsaw, Wolska, Warsaw, Poland; 11Tibotec BVBA, Beerse, Belgium; 12Tibotec Inc., Titusville, NJ, USA

44Presented at APASL, 18 February 2011 Presented at APASL, 18 February 2011

REALIZE: Study ObjectivesREALIZE: Study Objectives

• International, randomized, double-blind, multicentre, placebo-controlled Phase III trial

• Primary objective:– To evaluate superior efficacy (proportion of patients

achieving an SVR) of TVR-based therapy compared with standard treatment in patients within the prior relapser and prior-non-responder (partials/nulls) group

• Key secondary objectives:– Evaluation of effect of Peg-OFN/RBV lead-in on

efficacy of TVR-based treatment– Assessment of safety and tolerability of TVR-based

treatment

REALIZE Study Design (N=662)*

484 160 128Weeks

72

T12/PR48Peg-IFN + RBV

TVR + Peg-IFN + RBV

Pbo + Peg-IFN + RBV n=266 Follow-up

SVR assessment

TVR+ Peg-IFN + RBV

Peg-IFN + RBVT12(DS)/

PR48

n=264Follow-up

Pbo + Peg-IFN + RBV

*Randomization stratified by viral load and prior response; stopping rules applied for TVR (Weeks 4, 6, and 8) and Peg-IFN/RBV (Weeks 12, 24, and 36)

Peg-IFN = 180μg/week; RBV = 1000–1200mg/day; TVR = 750mg every 8 hoursClinicalTrials.gov identifier: NCT00703118

Pbo = placebo; DS = delayed start

Pbo/PR48 (control) Pbo +

Peg-IFN + RBV Peg-IFN + RBV

n=132

Follow-up

Presented at APASL, 18 February 2011 Presented at APASL, 18 February 2011

47

REALIZE: Baseline Characteristics

*Determined using the COBAS TaqMan HCV assay version 2.0; ‡Determined by NS3 sequencing; §Defined by local pathologists


REALIZE: SVR in Prior Relapsers, Partial Responders and Null Responders

SV

R (

%)

Prior relapsers

Prior partial responders

Pbo/PR48

4/27

T12/PR48

29/49

T12(DS)/PR48

26/48n/N=

Pbo/PR48

2/37

T12/PR48

21/72

T12(DS)/PR48

25/75

Pbo/PR48

16/68

T12/PR48

121/145

T12(DS)/PR48

124/141

Prior null responders

48*p<0.001 vs Pbo/PR48

**

**

**


T12/PR48 (n=266)

T12(DS)/PR48

(n=264)Pbo/PR48

(n=132)Discontinuation of All Study Drugs during TVR Treatment Phase, n (%)

Any AE

Rash events

Anemia events

Pruritus

17 (6)

2 (1)

2 (1)

0

11 (4)

2 (1)

2 (1)

1 (<1)

4 (3)

0

0

0

Discontinuation of TVR during TVR Treatment Phase, n (%)

Any AE

Rash events

Anemia events

Pruritus

39 (15)

12 (5)

6 (2)

1 (<1)

29 (11)

10 (4)

9 (3)

3 (1)

4 (3)

0

0

0

49

AEs Leading to Study Drug Discontinuations

AE = adverse event


REALIZE: ConclusionsREALIZE: Conclusions

• TVR/Peg-IFN/RBV was superior to Peg-IFN/RBV in treatment experienced populations including null responders, partial responders and relapsers

• A lead-in strategy using TVR-based regimen did not improve SVR rates or reduce on-treatment virologic failure and relapse rates

• Safety data were comparable to previous TVR studies. Adverse events leading to permanent discontinuation (anemia and rash) were more frequent in the pooled telaprevir group then in the control group

Presented at APASL 18 Feb 2011Presented at APASL 18 Feb 2011

CONCLUSIONS

• The future is very bright, with greater opportunity for CURE

• Boceprevir/Telaprevir associated with higher SVR rates • Shorter duration (response-guided therapy)

• Protease inhibitors & PegIFN/Ribavirin expected to be the next standard of care for HCV Genotype 1

CONCLUSIONS

• The future is very bright for our Treatment Failure patients

• Boceprevir/Telaprevir will set a new standard for our treatment-experienced

Jo-Ann Ford, RN, MSN Associate Director BC Hepatitis Program Diamond Centre, VGH Advances in HCV Treatment - Where Are we Going? Where Are we Going?

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