Eluvia Drug Eluting Stent:A Platform for success?

Prof. Giovanni Torsello, MD

Münster, 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.

• 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 predictive of results in other cases. Results in other cases may vary.

Disclosure

Speaker name: G Torsello

.................................................................................

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

Potential problems of SFA treatment

Timing of SFA restenosis is longer compared to coronary stenting, which predominantly occurs within 6 months after stenting

Iida, O. et al. Cath and Cardiov Intv. 2011;

78:611–617.

Kimura T, et al. N Engl J Med

Restenosis in the SFA peaks at around 12 months

• CE Mark February 2016

• Innova stent platform

•Self-expanding nitinol

• Biostable polymer matrix

• Paclitaxel

EluviaTM Drug-Eluting StentA platform for success

Boston Scientific Data on File.

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% thru 24M

The MAJESTIC Study (Eluvia): 0.0% thru 24M

Width, Length and angles

optimized for maximum

strength

Radial Force and Flexibility

must be matched by excellent

Fracture Resistance

Eluvia Drug Eluting StentPolymer Selection: PVDF-HFP on PBMA

Biocompatible

PROMUS polymer:

PBMA-PVDF

• 20k clinical patients studied

• Over 10M WW implants

Tunable

Time

Dru

g R

ele

ase

Ability To Tune Drug

Release

Durable

Durable coating during

deployment/fatigue testing

Dep

loy

Fo

rce

BPolymer A DC E

Deployable

BSC evaluated multiple biostable & biodegradable polymers

Boston Scientific Data on File.

Eluvia Drug Eluting Stent -Sustained drug release and tissue concentration over time-

• >90% of drug is released at 1 year

• Drug release coincides with the restenotic cascade

Based on pre-clinical PK analysis. Data on file at Boston Scientific.

*Dake MD, et al. J Vasc Interv Radiol. 2011;22(5):603-610.

Preclinical Evidence

BMS:DES:DES Preclinical StudyStudy Design and Methods

Kaluza, G. LINC 2016.

Pre-clinical results may not necessarily be indicative of clinical performance.

• 1:1:1 Eluvia : Zilver : Innova randomization

• Imaging: QVA and OCT

• Histology: Histomorphology and histomorphometry

• Histochemistry and Immunohistochemistry

Balloon Injury, Stent Implant

+ baseline imaging (pre &

post)

First imaging f/u for all

animals

-7 days Day 0 30 days 90 days 180 days

9 FHS:

Eluvia n=6

Zilver n=6

Innova BMS n=6

Second imaging prior to termination

and histology

High cholesterol diet for 180 days

Mean TC: 389±63 mg/dL 686±94 mg/dL 664±58 mg/dL

9 FHS:

Eluvia n=6

Zilver n=6

Innova BMS n=6

18 FHS:

Eluvia n=12

Zilver n=12

Innova BMS n=12

Familial Hypercholesterolemia Swine model

TC=total cholesterol

OCT Results: Neointimal Distribution at 30 and 90 Days (n=6) Interim

0.0

0.5

1.0

1.5

2.0

2.5

1 2 3 4 5 6 7 8 9

Ne

oin

tim

al t

hic

kne

ss (

mm

)

Stent Segment

Neointimal Distribution - BMS

30-Day 90-Day

0.0

0.5

1.0

1.5

2.0

1 2 3 4 5 6 7 8 9

Ne

oin

tim

al t

hic

kne

ss (

mm

)

Stent Segment

Neointimal Distribution - Eluvia DES

30-Day 90-Day

0.0

0.5

1.0

1.5

2.0

1 2 3 4 5 6 7 8 9

Ne

oin

tim

al t

hic

kne

ss (

mm

)

Stent Segment

Neointimal Distribution - Zilver PTX DES

30-Day 90-Day

1.27

0.20 0.22

1.29

0.500.89

0.0

0.5

1.0

1.5

2.0

Control BSC Eluvia DES Zilver PTx DES

mm

Neointimal Thickness

Kaluza, G. LINC 2016. Pre-clinical results may not necessarily be indicative of clinical performance.

BMS:DES:DES Preclinical StudyAngio & OCT Images from Day 0 to Day 90

BMS Day 0 Zilver Day 0 Eluvia Day 0

Kaluza, G. LINC 2016. Pre-clinical results may not necessarily be indicative of clinical performance.

BMS:DES:DES Preclinical StudyAngio & OCT Images from Day 0 to Day 90

Kaluza, G. LINC 2016. Pre-clinical results may not necessarily be indicative of clinical performance.

BMS Day 90 Zilver Day 90 Eluvia Day 90

Clinical Evidence

BSC Peripheral BMS/DES Clinical Program

Prospective, multicentre, single-arm, open label

n = 299 (2yr follow-up complete)

Prospective, multicentre, single-arm, open label

n= 57 (2yr follow-up complete)

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

n = 485 (Enrolling)

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/orProximal 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 the SFA

Clinicaltrials.gov Identifier: NCT01820637

MAJESTIC Clinical Study

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%

MAJESTICBaseline Information

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)Baseline Patient Characteristics (N=57)

12 Months 24 Months

Primary Patencya 96.4% 78.2%

Assisted Primary Patencyb 98.2% 84.7%Note: Kaplan-Meier Estimates.aDuplex ultrasound peak systolic velocity ratio ≤2.5 and absence of TLR or bypass.bNo TLR and those with TLR not for complete occlusion or bypass who were free of restenosis at 24 months.

MAJESTICOverall Efficacy & Safety

24-Month Safety Profile• 92.5% (49/53) TLR free rate

– Only 2 additional TLRs were reported between one and two years

• No target limb major amputations

• 1 death at >365 days post-procedure, unrelated

Stent Integrity• No stent fractures

TLR, target lesion revascularization.

At risk: 56 53.5 36.5

Time Post-procedure (months)

Cu

mu

lati

ve T

LR

-Fre

e R

ate

MAJESTIC 24-Month Freedom from TLRKaplan-Meier Estimate

91.3%

96.4%

Müller-Hülsbeck, S. CIRSE 2016.

ABI, ankle-brachial indexMüller-Hülsbeck, S. CIRSE 2016.

MAJESTICPatient Outcomes: 24 months

0%

20%

40%

60%

80%

100%

Baseline (N=57) 1 Month (N=56) 12 Months (N=53) 24 Months (N=53)

Pe

rce

nta

ge o

f P

atie

nts

Rutherford Category

6

5

4

3

2

1

0

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

• ABI improvement sustained through 24 months

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)

12 Months(N=51)

24 Months(N=47)

AB

I

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

No occlusion, severe calcification, or

diabetes (N=5)

TLR 12.0% 9.1% 5.9% 0%

MAJESTIC – SubgroupsSevere Calcification, Occlusion, Diabetes – 24M

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

24-Month Freedom from TLR

Müller-Hülsbeck, S. VIVA 2016.

Study Overview: Site Registry

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

Objective To assess the performance of Eluvia DES in all comers with femoropopliteal arterial occlusive disease

Study Design Retrospective, single-arm, single-centre non-randomized clinical study

Subjects 100 patients

Follow-up 3 or 6 months, and 12 months (DUS, X-ray, ABI, Rutherford)

Primary Endpoint Primary patency

Secondary Endpoints • Technical success (no residual stenosis > 30%)• Secondary patency• Target lesion revascularisation• Stent-fracture• Clinical improvement (Rutherford categories)• Major adverse limb event (Major amputation and/or reintervention)• Any procedure-related or device-related major adverse event

Inclusion Criteria • PAD Rutherford categories 3-6• De novo or restenotic lesions with stenosis > 70% (angiographically assessed) and suboptimal

result after PTA (elastic recoil, severe residual stenosis or flow-limiting dissection)

Independent study sponsored and funded by G. Torsello and Münster University Hospital .

Waiting for the EMINENT TRIALMünster all-comers registry

*Tigris stent (GORE MEDICAL) for p2 segment (n=4)

Eluvia™ DESMünster Registry

Lesion Characteristics Characteristics N

TASC II

A 2 (4%)

B 20 (37%)

C 4 (7%)

D 32 (55%)

Occlusion 46 (79%)

Vessel diameter (median, IQR, in mm) 6 (5-6)

Lesion Length (mean ± SD, in mm) 195 ± 104

Calcification 42 (72%)

Severe 13 (22%)

Extent of the lesion

Proximal SFA 29 (50%)

Middle SFA 40 (69%)

Distal SFA 45 (78%)

P1 25 (43%)

P2 4 (7%)*

P3 0

Independent study sponsored and funded by G. Torsello and Münster University Hospital .

Characteristics N

Number of stents / patient1 234

29 (54%)19 (35%)

5 (9%)1 (2%)

Diameter of stents (in mm) 6

Stent length (mean ± SD, in mm) 196 ± 103

Additional procedures

Atherectomy (P2 segment) 1 (2%)

Rotational thrombectomy 1 (2%)

DCB in other lesion 11 (20%)

Viabahn (AV fistula) 1 (2%)

Tigris stent (P2-P3) 2 (4%)

Patchplasty of the commonfemoral artery

2 (4%)

Lesion Characteristics

Eluvia™ DESMünster Registry - Case

Independent study sponsored and funded by G. Torsello and Münster University Hospital .

Post PTA

Eluvia™ DESMünster Registry - Case

Independent study sponsored and funded by G. Torsello and Münster University Hospital .

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

• Preclinical evidence suggests that :• Both DES continued to be superior to BMS in terms of restenosis • In contrast to the 30-day data, Eluvia demonstrated significantly lower amount of

neointima than Zilver

• The MAJESTIC 24-month results demonstrated: • Freedom from TLR rate of 92.5% (49/53)• Zero stent fractures observed• Symptomatic and hemodynamic improvement • Low reintervention rates achieved in subgroups of patients with challenging

baseline characteristics (ie, diabetes, total occlusion, severe calcification)

• The Eluvia Registry Münster includes a patient group with longer more complex lesions (55% TASC II D) than patients in the typical RCTs.

• Boston Scientific’s Peripheral Drug Eluting Stent Clinical program is a robust series of studies aimed to provide further data about the Eluvia DES

Universitätsklinik Münster St. Franziskushospital Münster

home page: www.gefaesschirurgie-muenster.de

Thank you !

Eluvia Drug Eluting Stent:A Platform for success?

Prof. Giovanni Torsello, MD

Münster, Germany