Majestic 3 year data

Chong Tze Tec

Head, Department of Vascular Surgery Singapore General Hospital

Disclosure

Speaker name:

Chong Tze Tec

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

• Drug eluting stent (DES) for PAD

• Clinical consideration for DES

• MAJESTIC 3 year data

Drug-Eluting Stents for Peripheral Arterial Disease

Clinical Application

Prolong stent patency

DES for Peripheral Applications: Intended Clinical Benefit

• Scaffolding prevents vessel shrinkage

• Anti-proliferative drugs (eg, paclitaxel) counteract

neointimal response to stenting

• Clinical trials of drug-eluting stents have shown improved stent patency following treatment of femoropopliteal2 and below-the-knee3,4 lesions

1Costa MA. Circ 2005; 2Dake MD, et al. Circ Cardiovasc Interv. 2011; 3Bosiers M, et al. J Vasc Surg. 2012; 4Rastan A, et al. Eur Heart J. 2011.

Minimize negative vessel remodeling

and proliferative response1

EluviaTM Drug-Eluting Vascular Stent System

• CE Mark February 2016

• Innova stent platform

• Self-expanding nitinol

• Biostable polymer matrix

• Paclitaxel

• 6F Tri-axial SDS, 0.035” guidewire compatible

• Blue Tri-Ax shaft fixed as the clear middle shaft is retracted releasing stent during deployment

Balanced geometry designed for even

stress distribution and optimal radial strength

Eluvia Drug-Eluting Stent:Stent Architecture

Spacing of interconnects

provides balanced stress

distribution for all deformation

modes

Stent Fracture rates in studies using the INNOVA Stent platform:

• SuperNOVA Study (Innova): 2.2% at 24M

• The MAJESTIC Study (Eluvia): 0.0% at 24M

Width, Length and angles

optimized for maximum

strength

Radial Force and Flexibility

must be matched by

excellent Fracture

Resistance

Eluvia Coating Design

• Dual Layer System

• Conformal Coating for Both Layers

• Primer Layer (PBMA): Promotes Adhesion of Active Layer to Stent

• Active Layer (PTx, PVDF-HFP)– Controls Release of Paclitaxel

o 0.167µg PTx/mm2 stent surface area

Stent

PBMA Primer Layer

Paclitaxel/PVDF-HFP Active Layer

Boston Scientific Data on File.

Considerations for DES in Peripheral Artery Disease

Clinical Application

Leave Nothing Behind?

‘Leave nothing behind’ strategy is based on the belief that

leaving no scaffold allows for future intervention options:

• Stent

• Bypass

• Repeat PTA

Is this strategy carrying over into clinical studies and real

world use?• Stenting studies have shown 40-50% acute PTA failures

received stents1,2

• Provisional stenting in DCB studies ranges from 2-50% -varies due to study design and lesion complexity

1Dake M et al. Circ Cardiovasc Interv 2011. 2Laird J et al. Circ Cardiovasc Interv 2010.

Stents used in DCB studies

• Stents are utilized in DCB studies • Real world DCB studies show higher rates of provisional stenting

Provisional Stenting in Randomized Controlled Trials may not be representative of actual stenting in studies due to study

design

Results from different trials are not directly comparable. Information provided for educational purposes.

FEMPAC- Werk M et al. Circulation 2008

RANGER SFA-Bausback et al. J Endovasc Ther 2017

PACIFIER- Werk et al. Circ Cardiovasc Interv 2012

THUNDER- Tepe G et al. N Engl J Med 2008

IT Registry- Micari A Et al. J Am Coll Cardiol Intv 2012

IN.PACT SFA- Tepe et al. Circulation 2015

Lutonix Registry- Thieme M, et al. JACC Cardiovasc Interv. 2017

CONSEQUENT- Tepe et al. Cardiovasc Intervent Radiol 2017

Bad Krozingen- Zeller T et al. J Endovasc Therapy 2014;

Leipzig Registry- Schmidt A, et al. JACC Cardiovasc Interv. 2016

ILLUMENATE FIH- Schroeder H et al. Catheter Cardiovasc

Interv 2015

ILLUMENATE EU RCT- Schroeder et al, Circulation 2017

ILLUMENATE US RCT- Krishnan et al, Circulation 2017

In.PACT Global Registry- Ansel G. TCT 2015

Ranger All-Comer Registry- Lichtenberg, M. CIRSE 2017

12 Month Primary Patency

100% 100% 100%90% 90% 88%

50% 50%

0%

20%

40%

60%

80%

100%

1a 1b 2a 2b 3a 3b 4a 4b

Minimal Calcificationa High Calcification

Lesion Calcification and Drug-Coated Balloon Efficacy

• 60 patients with SFA stenosis or occlusion treated with DCB

• 50% primary patency rates in heavily calcified SFA lesions, regardless of lesion length

• Greater calcification was associated with poorer outcomes at 1 year:

- Lower patency

- Greater TLR rate

- Lower ankle-brachial index

- Greater late lumen loss

DCB, drug-coated balloon; SFA, superficial femoral artery; TLR,

target lesion revascularization.

Fanelli F, et al. Cardiovasc Intervent Radiol. 2014 ;37(4):898-907.

aCalcium burden quantified with computed tomography

angiography (CTA), digital subtraction angiography

(DSA), and intravascular ultrasound (IVUS).

Study conducted using Medtronic IN.PACT® Admiral® DCB

Leave nothing behindShift in strategy?

• The strategy of leaving nothing behind is based on the assumption that a future intervention is inevitable…

• What is the threshold to shift thinking?

- Is there a maximum for reintervention rates?

- Threshold for stent fracture rate?

- In certain lesions, should DES be the go to strategy?

BSC Peripheral BMS/DES Clinical Program

Prospective, multicentre, single-arm, open label

n = 299 (3yr follow-up complete)

Prospective, multicentre, single-arm, open label

n= 57 (3yr follow-up complete)

Prospective, multicentre, RCT 2:1 (Eluvia : Zilver PTX)

n = 485 (Enrollment Complete)

Prospective, multicentre, RCT 2:1 (Eluvia : BMS)n = 750 (Enrolling)

Prospective, multicentre, single-arm, open labeln = 500 (Enrolling)

IMPERIAL(DES)

MAJESTIC(DES)

SuperNOVA(BMS)

EMINENT(DES/BMS)

REGAL(DES)

Study Overview: MAJESTIC

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

Objective Evaluate the performance of Eluvia DES System when treating Superficial 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)No center to enroll > 20% (11 subjects) of the total study population

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

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

Eluvia™ Drug-Eluting Vascular Stent System for SFA: MAJESTIC Clinical Study

Clinicaltrials.gov Identifier: NCT01820637

MAJESTIC Clinical Study

MAJESTIC 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

Key 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.

Baseline Patient Characteristics (N=57)

Demographics

Age (Years) 69.3±9.3

Male Gender 82.5%

Race/Ethnicity

Caucasian 94.7%

Asian 1.8%

Other 3.5%

General Medical History

Smoking 87.7%

Current Diabetes Mellitus 35.1%

Hyperlipidemia 63.2%

Hypertension 73.7%

Cardiac History

Coronary Artery Disease 38.6%

Myocardial Infarction (MI) 15.8%

Congestive Heart Failure 5.3%

Peripheral Vascular History

Peripheral Vascular Surgery 5.3%

Other Peripheral Endovascular Interventions 24.6%

History of Claudication 89.5%

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

Baseline 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.

Overall Efficacy & Safety

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 fracturesa

At risk: 56 54 51.5 30

Cum

ula

tive

TL

R-F

ree

Rate

Time Post-procedure (months)

36-Month Freedom from TLRKaplan-Meier Estimate

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. CIRSE 2017. Müller-Hülsbeck S. et al, Cardiovasc Interv Radiol 2017, doi: 10.1007/s00270-017-1771-5.

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

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

00.94±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)

12 Months(N=51)

24 Months(N=47)

AB

I

Müller-Hülsbeck, S. CIRSE 2016. Müller-Hülsbeck S. et al, Cardiovasc Interv Radiol 2017, in press.

TLR free rates for SFA DES trials24 months

Results from different trials are not directly comparable. Information provided for educational purposes.

Müller-Hülsbeck, S. CIRSE 2016.

Dake, M. et al. J of Am Coll of Cardiol. 2013.

Subgroup Analysis Severe Calcification, Occlusion, Diabetes

MAJESTIC study sample included:

• 20 with diabetes (35.1%)

• 26 patients with total occlusions at baseline (46%)

• 37 with core-lab determined severe calcification (64.9%)

• Subgroups not mutually exclusive

Diabetes

Total Occlusion

Severe Calcification

n=4

No diabetes,

occlusion, or severe

calcification

(n=5)

n=11 n=10

n=4

n=11 n=1

n=11

Müller-Hülsbeck, S. VIVA 2016.

Occlusion (N=26) Severe Calcification (N=37) Diabetes (N=20)

fTLRa 84.3% 85.5% 82.4%a Kaplan-Meier estimate at 1095 days.

Subgroup Analysis – 3 YearsSevere Calcification, Occlusion, Diabetes

• Low reintervention rates among patients with challenging medical and lesion characteristics at baseline

Müller-Hülsbeck S. et al, Cardiovasc Interv Radiol 2017, doi: 10.1007/s00270-017-1771-5.

3-Year Freedom from TLR

Cu

mu

lative

Eve

nt-

Fre

e R

ate

Months Since Index Procedure

Sev Calc Occl DM

Conclusions

• The Eluvia Drug-Eluting Stent is designed to:

- Optimize flexibility, radial strength, and fracture resistance in the SFA

- Sustain drug release when restenosis is most likely to occur

• In a swine model of femoral restenosis, Eluvia was associated with lower levels

of neointimal proliferation and a sustained biological effect at 90 days compared

with a polymer-free stent-based approach

• MAJESTIC long term follow up demonstrated:

- 83.5% primary patency at 2 years

- Freedom from TLR rate of 85.3% at 3 years

- Symptomatic and hemodynamic improvement

- Low reintervention rates achieved in subgroups of patients with challenging baseline

characteristics (i.e., diabetes, total occlusion, severe calcification)

• Boston Scientific’s Peripheral Drug-Eluting Stent Clinical program is a robust

series of studies aimed to provide further data about the Eluvia DES

• DES show promising results for PAD treatment in select patient populations and

may yield relative cost savings in certain clinical situations

Thank You

Majestic 3 year data

Chong Tze Tec

Head, Department of Vascular Surgery Singapore General Hospital