Lessons from IMPERIAL RCT (ELUVIA vs. ZILVER PTX) · Thomas Zeller, MD For the 12 months preceding this presentation, I ... (PPA) lesions up to 110mm in length Study Design Prospective,

Lessons from IMPERIAL RCT (ELUVIA vs. ZILVER PTX)

Prof. Thomas Zeller

Bad Krozingen,Germany

• IMPORTANT INFORMATION: These materials are intended to describe common clinical considerations and procedural steps for the on-label use of referenced technologies as well as current standards of care for certain conditions. Of course, patients and their medical circumstances vary, so the clinical considerations and procedural steps described may not be appropriate for every patient or case. As always, decisions surrounding patient care depend on the physician’s professional judgment in light of all available information for the case at hand.

• Boston Scientific Corporation (“BSC”) does not promote or encourage the use of its devices outside their approved labeling.

• The presenter’s experience with BSC products may not be interpreted or relied upon to support clinical claims about BSC devices or product comparison claims regarding BSC and competitive devices. The experiences of other users may vary.

• Results from case studies are not necessarily predictive of results in other cases. Results in other cases may vary.

Thomas Zeller, MD

For the 12 months preceding this presentation, I disclose the following types of financial relationships:

• Honoraria received from: Abbott Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Philips-Spectranetics, TriReme, Veryan, Shockwave, Biotronik, B. Braun

• Consulted for: Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics, Veryan, Intact Vascular, Veryan

• Common stock: QT Medical

BSC PI Drug-Eluting Stent Clinical Program

IMPERIALMulticenter, Head to Head RCT 2:1(Eluvia : ZilverTMPTXTM)

N = 465 2Y follow up complete

MAJESTICMulticenter, single-arm(Eluvia)

N = 57 3Y follow up complete

EMINENTMulticenter, RCT 2:1(Eluvia : BMS)

N = 750 Enrolling

REGALMulticenter registry(Eluvia)

N = 500 Enrolling

SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)

N = 222 Enrolling

SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm

N = 201 & N = 100

Enrolling

*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.

Study Overview: MAJESTIC

Device Eluvia™ Drug-Eluting Vascular Stent System (Boston Scientific)

Objective Evaluate the performance of Eluvia DES System when treatingSuperficial Femoral (SFA) and/or Proximal Popliteal Artery (PPA)lesions up to 110mm in length

Study Design Prospective, multicentre, single-arm, open label

Subjects 57 patients with femoropopliteal artery lesions

Investigational Centers

14 sites (Europe, Australia, New Zealand)

Follow-up Baseline, Procedure 1 month, 9 months, 1 year, 2 years, 3 years

PrimaryEndpoint

Primary patency of target lesion at 9 months• Primary endpoint met: 9M patency

Müller-Hülsbeck S, et al. J Endovasc Ther 2016.

MAJESTIC Clinical Study

Safety, Efficacy, Patient Outcomes• Clinical Events Committee-

adjudicated MAE• All-cause death (through

1M)• Target limb major

amputation• TLR• Core lab-adjudicated

primary patency• Rutherford classification• ABI

MAJESTIC Clinical StudyKey Eligibility Criteria• Chronic lower limb

ischemia defined as Rutherford categories 2, 3, or 4

• De novo or restenotic lesions (≥70% stenosis) in the native SFA or proximal popliteal artery

• Reference vessel diameter 4-6 mm

• Total lesion length ≥30 mm and ≤110 mm

Müller-Hülsbeck S, et al. J Endovasc Ther 2016.

MAJESTICBaseline Lesion Characteristics (Core Lab)

Arterial Segments

Ostial 0.0%

Proximal 1.8%

Mid 59.6%

Distal 77.2%

Proximal Popliteal 8.8%

Length (mm) 70.8±28.1

Calcification

None/Mild 21.1%

Moderate 14.0%

Severe 64.9%

Percent Diameter Stenosis 86.3%±16.2%

Occlusions 46%

Minimum Lumen Diameter (mm) 0.7±0.8

Reference Vessel Diameter (mm) 5.2±0.8

Patency to Foot

No Infrapopliteal Vessel Patent 5.3%

1 Vessel Patent 28.1%

2 Vessels Patent 31.6%

3 Vessels Patent 22.8%

Müller-Hülsbeck S, et al. J Endovasc Ther 2016.

12 Months 24 Months

TLR 96.4% 92.8%

Primary Patencyb 96.4% 83.5%

Assisted Primary Patencyc 98.2% 88.9%Note: Kaplan-Meier estimates.bDuplex ultrasound peak systolic velocity ratio ≤2.5 and absence of TLR or bypass. cNo TLR and those with TLR not for complete occlusion or bypass who were free of restenosis at 24 months.

MAJESTIC Overall Efficacy & Safety

aX-ray evaluation with angiographic verification

were performed at 12 and 24 months. No

fractures were reported in relation to adverse

events through 3 year follow up.Müller-Hülsbeck S. et al, Cardiovasc Interv Radiol 2017;40(12):1832-1838.

36-Month Safety Profile• 85.3% freedom from TLR

rate (K-M estimate)• No target limb major

amputations• 2 deaths at >365 days post-

procedure, unrelated to study device or procedure

Stent Integrity• No stent fracturesaAt risk: 56 54 51.5 30

Cu

mu

lative

TL

R-F

ree

Rate

Time Post-procedure (months)

36-Month Freedom from TLRKaplan-Meier Estimate

ABI, ankle-brachial index

0%

20%

40%

60%

80%

100%

Baseline(N=57)

1 Month(N=56)

12 Months(N=53)

24 Months(N=53)

Per

cen

tage

of

Pat

ien

ts

Rutherford Category

6

5

4

3

2

1

0

0.94±0.22

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Baseline(N=51)

1 Month(N=53)

12Months(N=51)

24Months(N=47)

AB

I

MAJESTIC Patient Outcomes 24 months

• 91% of patients with no or minimal symptoms (Rutherford Category 0-1) at 24 months

• ABI improvement sustained through 24 months

Müller-Hülsbeck S. et al, Cardiovasc Interv Radiol 2017;40(12):1832-1838.

BSC PI Drug-Eluting Stent Clinical Program

IMPERIALMulticenter, Head to Head RCT 2:1(Eluvia : ZilverTMPTXTM)

N = 465 2Y follow up complete

MAJESTICMulticenter, single-arm(Eluvia)

N = 57 3Y follow up complete

EMINENTMulticenter, RCT 2:1(Eluvia : BMS)

N = 750 Enrolling

REGALMulticenter registry(Eluvia)

N = 500 Enrolling

SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)

N = 222 Enrolling

SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm

N = 201 & N = 100

Enrolling

*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.

IMPERIAL Study Devices

Eluvia™ DES

Boston Scientific

Zilver® PTX®

Cook Medical

Stent Platform Innova Zilver Flex

Material Nitinol Nitinol

PolymerBiostable Fluorinated

Polymer Matrix (PROMUS polymer)

None

Drug

Dose DensityPaclitaxel

0.167µg/mm2

Paclitaxel

3 µg/mm2

Deployment Self-expanding Self-expanding

SizesDiameter Length Diameter Length

6-7 mm 40-150 mm 6-8 mm 40-120 mm

BSC Data on file. Cook Medical (2014). Zilver PTX Drug-Eluting Peripheral Stent Instructions for Use.

Inclusion

• Rutherford category 2, 3, or 4

• Lesions in the native

SFA and/or PPA

• Stenosis ≥70% by visual

angiographic assessment

• Vessel diameter 4-6 mm

• Total lesion length 30-140 mm

Exclusion

• Target lesion/vessel

previously treated with DCB

(<12 months prior) or

previously stented

• Prior surgery of the SFA/PPA

in the target limb

• Use of atherectomy, laser or

other debulking devices

• Dialysis

Key Eligibility Criteria

DCB, drug-coated balloon; SFA, superficial femoral artery; PPA, proximal popliteal artery

Gray WA, Lancet 2018.

Baseline Lesion Characteristics

Eluvia (N=309) Zilver PTX (N=156)

Arterial Segments

Ostial 1.6% 0.6%

Proximal SFA 12.9% 10.3%

Mid SFA 65.0% 66.7%

Distal 66.3% 65.4%

Proximal Popliteal Artery 18.0% 12.7%

Lesion length (mm) 86.5 ± 36.9 81.8 ± 37.3

Calcification

None/Mild 36.5% 32.3%

Moderate 22.8% 34.8%

Severe 40.1% 32.3%

Reference Vessel Diameter (mm) 5.0 ± 0.8 5.1 ± 0.8

% Diameter Stenosis 80.7% ± 16.5% 80.8% ±16.4%

<50% 1.6% 1.9%

50%-<100% 67.2% 67.7%

100% (Occlusion) 31.2% 30.3%

Angiographic Core Laboratory DataGray WA, Lancet 2018.

2 YEAR RESULTS

IMPERIAL Head to Head RCT

Iida O, VIVA 2019

Intention to treat. Kaplan-Meier estimate with standard errors. Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of

clinically-driven target lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab. Kaplan-Meier estimate

utilizing time-to-event of clinically-driven TLR up to 730 days and duplex ultrasound data at 24 months.

Pri

ma

ry P

ate

nc

y R

ate

(%

)

0%

70%

80%

90%

100%

0%

20%

40%

60%

80%

100%

Cu

mu

lati

ve E

ven

t F

ree (

%)

EluviaZilver PTX

Months Since Procedure

0 2 4 6 8 10 12 14 16 18 20 22 24

Error bars are SE.

Log-rank

p=0.10

83.0%Eluvia

77.1%Zilver PTX

Effectiveness I Primary Patency at 24 Months

• 24-month all-cause mortality 7.1% (21/295) for Eluvia and 8.3% (12/145) for Zilver PTX (p=0.6649)

• Freedom from MAE 85.8% vs 79.9% (p=0.1236)

• Significantly lower clinically-driven TLR rate for Eluvia vs Zilver PTX (12.7% vs 20.1%; p=0.0495)

• FDA has reviewed the latest data submitted by Boston Scientific regarding peri-stent inflammation as seen on transverse DUS and has confirmed that current labeling requires no change

Safety at 24 Months

Intention to treat. Clinical Events Committee-adjudicated adverse events included major adverse events (MAE), all deaths, and stent thrombosis. MAEs defined

as all causes of death through 1 month, target limb major amputation through 24 months, and target lesion revascularization (TLR) through 24 months. Dual

antiplatelet therapy recorded as acetylsalicylic acid and one of clopidogrel, ticlopidine, prasugrel or ticagrelor. DUS, duplex ultrasound.

Eluvia Zilver PTX p24-Month MAE 14.2% (39/275) 20.1% (27/134) 0.1236

Any death at 1 month 0% 0% UndefTarget limb major amputation 1.5% (4/275) 0.7% (1/134) >0.99TLR 13.5% (37/275) 20.1% (27/134) 0.0803

Clinically-driven TLR 12.7% (35/275) 20.1% (27/134) 0.0495Non-clinically-driven TLR 0.7% (2/275) 0.0% (0/134) >0.99

Stent thrombosis 3.1% (9/295) 4.1% (6/145) 0.5818Antiplatelet use at 24 months

Acetylsalicylic acid 87.5% (224/256) 90.4% (113/125) 0.4057Dual antiplatelet therapy 53.9% (138/256) 52.8% (66/125) 0.8389

Iida O, VIVA 2019. BSC Data on file.

2 YEAR RESULTS

IMPERIAL RCT Subgroups:

Occlusion, Calcification, Diabetes

Primary Patency at 24 MonthsEluvia Treatment Arm

• High patency rates for patients treated with Eluvia DES, regardless of lesion or patient complexity

Error bars are SE.Gray W, LINC 2020. Kaplan-Meier estimate utilizing time-to-event of clinically-driven TLR up to 730 days and duplex ultrasound

data at 24 months. Diabetes = medically-treated diabetic patients.

Occlusion

Log-rank p=0.0548

Non-CTO 85.7%CTO 76.4%

0 6 12 18 24

Months Since Procedure

0%

50%

100%

Cu

mu

lati

ve E

ven

t-Fr

ee (

%)

Calcification

Log-rank p=0.0943

Moderate/severe 85.0%None/mild 78.6%

0 6 12 18 24

Months Since Procedure

0%

50%

100%

Diabetes

Log-rank p=0.5325

Diabetes 85.7%No Diabetes 82.5%

0 6 12 18 24

Months Since Procedure

0%

50%

100%

Cu

mu

lati

ve E

ven

t-Fr

ee (

%)

• For patients treated with Eluvia, similar MAE rates regardless of lesion or patient complexity

– Significantly lower CD-TLR rate for moderate/severe calcification vs none/mild

Safety at 24 MonthsEluvia Treatment Arm: Occlusion, Calcification, Diabetes

Gray W, LINC 2020. Intention to treat. Clinical Events Committee-adjudicated adverse events included

target limb major amputation, target lesion revascularization (TLR), and stent thrombosis.

Eluvia Drug-eluting Stent Arm

Occlusion Calcification Diabetes

Yes

(n=96)

No

(n=212) p

Mod/Sev

(n=193)

None/

Mild

(n=112) p

Medically-treated (n=116)

No(n=180) p

Target limb major amputation

1.1% 1.6% >0.99 1.2% 2.0% 0.6303 3.0% 0.6% 0.1554

TLR(CD-TLR & non-CD-TLR)

17.2% 11.8% 0.2169 10.6% 18.8% 0.0566 13.0% 13.5% 0.9083

Stent thrombosis 4.3% 2.5% 0.4681 2.2% 4.7% 0.2967 0.9% 4.7% 0.0919

17.2%9.4% 12.0%10.7%

18.8%12.9%

0%

10%

20%

30%

Occlusion Calcification Diabetes

Clin

ical

ly-d

rive

n

TLR

p=0.1307 p=0.0257 p=0.8337

24 Month ResultsDiabetes (Eluvia vs Zilver PTX)

Kaplan-Meier Analysis of Primary Patency

Eluvia(n=116)

Zilver PTX (n=64) p

Target limb major amputation 3.0% 1.8% >0.99TLR(CD-TLR & non-CD-TLR)

13.0% 23.6% 0.0899

Stent thrombosis 0.9% 8.2% 0.0212

12.0%

23.6%

0%

10%

20%

30%

Eluvia Zilver PTX

p=0.0595

Clinically-Driven TLR

Gray W, LINC 2020. Medically-treated diabetic patients.

0 6 12 18 24

Months Since Procedure

0%

50%

100%

Cu

mu

lati

ve E

ven

t-Fr

ee (

%)

Log-rank p=0.1255

Eluvia 85.7%

Zilver PTX 77.6%

Conclusions

• MAJESTIC first-in-human study demonstrated exceptional patency for Eluvia DES, which was repeated in the IMPERIAL head-to-head RCT

• In IMPERIAL through 24 months:

– Significantly lower clinically-driven TLR rate for Eluvia vs Zilver PTX (12.7% vs 20.1%; p=0.0495)

– Excellent primary patency rate sustained with Eluvia DES (83.0%KM estimate)

– High patency rates for patients treated with Eluvia, regardless of lesion or patient complexity

– Low mortality rate at 24 months

Lessons from IMPERIAL RCT (ELUVIA vs. ZILVER PTX)

Prof. Thomas Zeller

Bad Krozingen,Germany