Future trials with drug eluting technologies · • All cause death through 1 month • Target limb major amputation through 12M • Target lesion revascularization (TLR) through

Future trials with drug eluting technologies

G. Torsello

Münster, Germany

Disclosure

Speaker name:

......................G. Torsello...........................................................

I have the following potential conflicts of interest to report:

X Consulting (Medtronic, Cook, Cordis, Boston, Gore)

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

COMPARE I*Multicenter, RCT 1:1(Ranger : In.Pact)

N = 414Pilot N=150 24M complete.N=414 12M follow up complete

RANGER SFA (FIH)Multicenter, RCT 2:1(Ranger : PTA)

N = 105 36M follow up complete

Ranger SFA Registry* Multicenter, registry N = 172 24M follow up complete

Ranger II Global PivotalMulticenter, RCT 3:1(Ranger : PTA)


Ranger DCB China Multicenter, single-arm N = 123 Enrolling

RANGER-BTK* Single center, single-arm N = 30 12M follow up complete

DCB vs PTA in CLI and Crural Arteries*

Single center, RCT 1:1(Ranger : PTA)

N = 70 Enrolling

DCB Venoplasty in AV Fistula Stenosis (DeVA)*

Multicenter, RCT 1:1(Ranger : PTA)

N = 186Enrollment stop and follow up

BSC Peripheral DCB Clinical Program

*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.Ranger DCB is an investigational device and not available for sale in the US.

Head to Head

DCB trials rationale

RANGER II SFA Global Pivotal

Multicenter, RCT 3:1 (Ranger : PTA)

COMPARE IMulticenter, RCT 1:1

(Ranger : In.Pact)

RandomizationProportionate – PTA well described → 3:1

?equipoise → 1:1

ComparatorPTA standard of care

at time in US

Market leading comparative device

EMEA

Data generation Increase datapoints for DCB

Head to head Low risk strategy High risk strategy

COMPARE I*Multicenter, RCT 1:1(Ranger : In.Pact)

N = 414Pilot N=150 24M complete.N=414 Enrollment complete

RANGER SFA (FIH)Multicenter, RCT 2:1(Ranger : PTA)


Ranger SFA Registry* Multicenter, registry N = 172 12M follow up complete

Ranger II Global PivotalMulticenter, RCT 3:1(Ranger : PTA)


Ranger DCB China Multicenter, single-arm N = 123 Enrolling

RANGER-BTK*Single center, single-arm


DCB vs PTA in CLI and Crural Arteries*

Single center, RCT 1:1(Ranger : PTA)

N = 70 Enrolling

DCB Venoplasty in AV Fistula Stenosis

(DeVA)*

Multicenter, RCT 1:1(Ranger : PTA)

N = 186 Enrolling

BSC Peripheral DCB Clinical Program

*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.Ranger DCB is an investigational device and not available for sale in the US.

RANGER BTK CRURAL DCB

Objective A safety and efficacy study to evaluate Ranger drug-eluting balloon for below the

knee angioplasty in patients with critical limb ischemia

Randomized trial comparing drug coated balloon vs plain balloon angioplasty in critical limb ischemia and treatment of long lesions

in crural arteries

PI Marc Sapoval Torbjorn Fransson

Design Prospective, single centre, non-controlled, open-label

Prospective, single centre, randomized

Centres France Sweden

Population 30 patients 70 patients

Primary Efficacy Endpoint

Primary patency (no stenosis >50%) and Late Lumen Loss (LLL) of the Target Lesion measured by Quantitative Vascular Angiography (QVA) at 6 months adjudicated by independent core lab

12 month primary patency

Primary Safety Endpoint

Composite of all death and major amputation at 6 and 12 months

TLR, Event Free Survival, MRA analysis

RANGER DCB BTK Studies

12m FU complete Enrolment completing

BSC PI Drug-Eluting Stent Clinical Program

IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)

N = 465 2Y follow up complete

MAJESTICMulticenter, single-arm(Eluvia)


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.

Clinical Study Overview: EMINENT

Title A Randomized Trial Comparing the ELUVIA™ Drug-Eluting Stent versus Bare Metal Self-Expanding Nitinol Stents in the Treatment of Superficial Femoral and/or Proximal Popliteal Arteries

Coordinating Principal Investigators

Prof. Yann Goueffic, Nantes, France

Prof. Giovanni Torsello, Münster, Germany

Objective To confirm superior effectiveness of the ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 140 mm in length when compared against bare metal stents, and collect additional data including health economics data.

Study Design Prospective, multi-centre, single-blind, superiority trial (RCT)Randomized 2:1 (Eluvia : Self Expanding BMS)*Powered for 10% Primary Patency superiority*

Subjects 750 subjects to receive treatment Total lesion length (or series of lesions) ≥ 30 mm and ≤140 mmRutherford 2-4Stenosis ≥70% by visual angiographic assessment

Enrolling

EMINENT Clinical Study

CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.

Clinical Study Overview: EMINENT

Investigational Centers

Up to 75 study centres in up to 10 EU countries:• Germany, Austria, Belgium, United Kingdom, France, Italy, Spain, Switzerland,

The Netherlands (potentially Central Eastern Europe)

PrimaryEffectiveness Endpoint

Primary patency • Freedom from more than 50% stenosis based on PSVR ≤ 2.4• Assessed by duplex ultrasound (DUS) at 12 months post-procedure and

adjudicated by an independent core laboratory

Secondary Endpoint

Health Economics• Walking Improvement at 12 months assessed by change in Six Minute Hall Walk

(6MHW) from baseline

• Walking Improvement and Quality of Life Improvement assessed at 1 month, 6 months, 12 months, 24 months and 36 months assessed by change in Walking Impairment Questionnaire (WIQ) and EQ-5D™ from baseline

• Changes in healthcare utilization over time and associated health care costs

Follow-Up Index, 1m, 6m, 1-year (primary endpoint), 2-year, and 3-year

EMINENT Clinical Study


Soga et. al., J Atheroscler Thromb, 2019

• 12-month angiography

performed for 66 patients

from 4 Japanese institutions

enrolled in the IMPERIAL trial

• Late lumen loss was

significantly less for the

Eluvia group

Late Lumen Loss







N = 750 Enrolling


N = 500 Enrolling


N = 222 Enrolling


N = 201 & N = 100

Enrolling


Head to Head







N = 750 Enrolling


N = 500 Enrolling


N = 222 Enrolling


N = 201 & N = 100

Enrolling


Clinical Study Overview: REGAL

Title A Real World Evaluation of ELUVIA™ Drug-Eluting stent in All-Comers Superficial Femoral Artery and Proximal Popliteal Artery Disease

Primary Investigator Prof Carlo Setacci, Siena, Italy

Objective Collect additional data including health economics data to support the use of the ELUVIA Drug-Eluting Vascular Stent System for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions

Study Design Prospective, multi-centre, single-arm, open-label registry

Subjects 500 subjects at up to 30 study centres in up to 10 EU countries• Stenotic, restenotic or (re)occluded lesion(s) in the femoro-popliteal

arteries suitable for endovascular treatment

PrimaryEffectiveness Endpoint

Primary patency • Freedom from more than 50% stenosis based on PSVR ≤ 2.4• Assessed by duplex ultrasound (DUS) at 12 months post-procedure

Primary Safety Endpoint

Major Adverse Event (MAE) rate defined as:• All cause death through 1 month• Target limb major amputation through 12M• Target lesion revascularization (TLR) through 12M

Follow-Up Index, 1m, 6m, 1-year (primary endpoint), and 2-years (standard of care)

REGAL Clinical StudyEnrolling








N = 750 Enrolling


N = 500 Enrolling


N = 222 Enrolling


N = 201 & N = 100

Enrolling


Clinical Study Overview: SPORTS

TitleSequent Please Drug Coated Balloons Versus Primary Stent Application in Long SFA Lesions

Primary Investigator/ Sponsor

Gunnar Tepe, MD - RoMed Klinikum Rosenheim, Germany

InnoRa GmbH

ObjectiveCompare angiographic and clinical outcome of PTA with a paclitaxel coated balloon versus nitinol stent (paclitaxel-eluting or bare metal) with regard to restenosis development

Study DesignProspective, multicenter, RCT 1:1:1 (Eluvia DES: SeQuent Please PCB : Nitinol stent)

Subjects

Up to 222 patients

• Rutherford stage 2-4

• Occlusion or stenosis ≥70% of diameter and ≥13 cm length in the SFA and/ or PI-segment of popliteal artery

Investigational Centers

Up to 11 centers in Germany

Primary EndpointPercent diameter stenosis at 1 year post intervention in successfully treated patients by quantitative angiography

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. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.

SPORTSEnrolling







N = 750 Enrolling


N = 500 Enrolling


N = 222 Enrolling


N = 201 & N = 100

Enrolling


• Global Pivotal Trial of the SAVAL Drug-Eluting Vascular Stent System

• Differentiated technology selected for Expedited Access Pathway (EAP) designation by FDA+

• First Ever EAP in the Peripheral Branch of FDA

• Enrollment began Aug 2018

The SAVALTM Pivotal Trial

+FDA’s Expedited Access Pathway (EAP) program is intended for

breakthrough medical devices that demonstrate the potential to address

unmet medical needs for life threatening or irreversibly debilitating diseases.

CAUTION: Investigational device and not available for sale in the U.S.

• Dual Layer System (same as Eluvia)

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

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

• Dose: 0.236 µg PTx/mm2 stent surface area

SAVALTM Coating Design

SAVAL is an investigational device and not available for sale in the US. Boston Scientific Data on File.

Stent

PBMA Primer Layer

Paclitaxel/PVDF-HFP Active Layer

Title A Randomized Trial comparing the Drug-Eluting Stent (DES) Below the Knee (BTK) Vascular Stent System vs Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal Lesions in Subjects With Critical Limb Ischemia

Principal Investigators

Global: Jihad Mustapha, MD, FACC FSCA

US: Patrick J. Geraghty, MD, FACS, RPVIEU: Hans van Overhagen, MD, PhD, EBIRJapan: Masato Nakamura, MD, PhD

Objectives Demonstrate a superior patency rate and acceptable safety in below-the-kneearteries with lesions treated with the SAVAL Stent vs PTA.Secondary: To collect additional information on limb salvage and overall quality of life in this patient population.

Study Design Phase A- RCT Phase B- single arm

Global, prospective, multicenter, 2:1 randomized (SAVAL vs PTA)

Stent size 3.5 mm x 80 mm

Sequential, single-arm study to collect ongoing safety and effectiveness dataStent sizes: Diameters 3-4 mm; Lengths 30, 80, 120 mm

Patients ~201 subjects (2:1 randomization) ~100 subjects

• up to 50 study centers in the US, Europe, and Japan

Follow-UpOffice visits at 1, 3, 6, 12, 24, and 36 months post procedureTelephone follow-up at 18 and 30 months post procedure

SAVAL Clinical StudyEnrolling

SAVAL is an investigational device and not available for sale in the US. Boston Scientific Data on File.

• Data generation is expensive, time consuming and not without risk but ultimately underpins therapy area for advancement of patient outcomes.

• Head to Head trials answer relevant clinical questions :

Efficacy (TLR reduction) and subsequent health economics.

Long term safety

• Level 1 RCT data sets a bar for new entrants :

CE approval

EU MDR and global regulatory oversight

Evidence-based adoption

Conclusions

Future trials with drug eluting technologies

G. Torsello

Münster, Germany

Documents

Future trials with drug eluting technologies · • All cause death through 1 month • Target limb major amputation through 12M • Target lesion revascularization (TLR) through