Boston Scientific Corporation: DES Bioabsorbable Technologies

Slides:



Advertisements
Similar presentations
“Real World”: SVG, De Novo or Restenotic Coronary Artery Lesions Chronic Stable Angina, Silent Ischemia, Acute Coronary Syndromes Vessel Diameters:
Advertisements

3rd CEEGI Advisory Board1 Resolute in the DES era: Indications & Limitations Georgios I. Papaioannou, MD, MPH, FACC, FSCAI Athens Medical Center Cardiac.
2 Year Clinical Outcomes from the Pivotal RESOLUTE US Study Laura Mauri MD, MSc on behalf of the RESOLUTE US Investigators Brigham and Women’s Hospital.
As presented by Patrick W. Serruys, MD, PhD, FACC Principal Investigator Thoraxcentre - Erasmus University Rotterdam, The Netherlands PISCES Paclitaxel.
BIOSENSORS-CLINICAL UPDATE “LEADERS AND BEYOND” John E Shulze, CTO BIOSENSORS INTERNATIONAL GROUP Jan 29, 2010.
Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 1 Meredith ● EVOLVE overview ● TCT 2010 ● Washington, DC Slide 1 Clinical and Angiographic.
Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President Boston Scientific Corporation Why Boston Scientific Persists with the Two-Drug.
1 of Presented by Gregg W. Stone, MD, ACC PROMUS Stent is a private-labeled Xience V Everolimus Eluting Coronary Stent System manufactured.
A Prospective, Randomized Trial Evaluating a Paclitaxel-Eluting Balloon in Patients TReated with Endothelial Progenitor Cell CapTuring Stents for De Novo.
RESOLUTE US One-Year Clinical Outcomes from the Pivotal Multicenter RESOLUTE US Study Objective To evaluate the clinical effectiveness of the Resolute.
Endeavor 4: A Randomized Comparison of a Zotarolimus- Eluting Stent and a Paclitaxel- Eluting Stent in Patients with Coronary Artery Disease Martin B.
Boston Scientific Drug eluting stent program A Scientific Approach Identify therapeutic agent Identify appropriate polymer carrier Evaluate a broad range.
NEXT A Prospective, Randomized Trial Comparing Cre8, a Polymer-Free Stent Eluting Sirolimus, to a Paclitaxel-Eluting Stent Didier Carrié, MD,PhD On behalf.
Late Clinical Outcomes after Bioresorbable or Permanent Polymer Everolimus-Eluting Stents: 2-Year Results from the EVOLVE II Randomized Trial Dean J.
Real-world clinical experience with an everolimus eluting platinum chromium stent with an abluminal biodegradable polymer – a report from the Swedish Coronary.
Final five-year clinical outcomes in the EVOLVE trial: A randomised evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting stent Ian T.
Durable Polymer DES: 5 Year Outcomes RESOLUTE Update Sigmund Silber, MD FESC, FACC, FAHA Heart Center at the Isar Munich, Germany On Behalf of the RESOLUTE.
Synergy: Short DAPT Study
David E. Kandzari, MD on behalf of the BIONICS investigators
The OPTIMAX first-in-man study Mid-term clinical outcome of Titanium-Nitride-Oxide-coated Cobalt Chromium stents in patients with de novo coronary artery.
Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease: ABSORB III Trial 2-Year Results Stephen G. Ellis, MD,
My initial ABSORB experience Assoc. Prof. I. Petrov
XIENCE V vs TAXUS: Game Over! The Studies are Definitive
New Generation Resolute Integrity Drug-Eluting Stent Superior to Benchmark Xience Drug-Eluting Stent: Primary Endpoint Results from the PROPEL Study –
The Abbott Vascular DES Pipeline
Two-year clinical outcomes in the EVOLVE FHU trial: A randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting stent Ian Meredith.
Three-year results from the multicentre PROMUS Element European Post-Approval (PE-Prove) Registry: outcomes in 1010 unselected patients treated with a.
A Novel Abluminal Coated Sirolimus-Eluting Stent as a Treatment Option for Diabetic Patients: Results from an All-Comers Multi-center Study: the En-ABL.
Understanding Stent Deformation
MiStent SES® Program Technology and Clinical Data Update
Why I Don’t Believe in BRS as the Future Scaffold Technology
Regulatory Challenges for Biodegradable Scaffolds Approval
12 Month Outcomes in Patients with Diabetes Mellitus Implanted with a Resolute Zotarolimus-eluting Stent: Initial Results from the RESOLUTE Global Clinical.
Bioabsorbable DES and Biodegradable Polymers – FDA View
One DES Eluting Two Drugs: Is it Feasible?
Alexandra Lansky, MD Yale School of Medicine
Summary and Conclusion
Harmonized Assessment by Randomized Multicenter Study of OrbusNEich’s COMBO StEnt Japan-USA HARMONEE: Primary Report of A Randomized Trial of a Bioabsorbable.
ABSORB Japan: 3-year Clinical and Angiographic Results of a Randomized trial Evaluating the Absorb Bioresorbable Vascular Scaffold vs. Metallic Drug-eluting.
DES Bioabsorbable and DCB Technologies
LONG-DES II Trial Randomized Comparison of the Efficacy of Sirolimus-Eluting Stent Versus Paclitaxel-Eluting Stent in the Treatment of Long Native Coronary.
Bioresorbable scaffold: the advent of a new era in percutaneous coronary revascularisation Clinical Data Update Ron Waksman, MD, FACC Director, Cardiovascular.
On behalf of all principal COMPARE II investigators:
Novolimus Elution from a Biodegradable Polymer Coated Coronary Stent
EXCELLA Studies - Novolimus Elution from PLLA Polymer Coated Stents DESyne® and DESyne BD: Design Specifications and Clinical Updates Stefan Verheye,
Regulatory Challenges for Biodegradable Scaffold Approval
Insights from the IMPERIAL and MAJESTIC SFA Studies
A Randomized Trial of a Bioabsorbable Polymer-Based Metallic DES vs
The SYNERGY™ Biodegradable Program & EVOLVE Clinical Trials
Regulatory Considerations for Coronary Drug Coated Balloons – FDA View
On behalf of J. Belardi, M. Leon, L. Mauri,
FINAL FIVE-YEAR CLINICAL OUTCOMES OF THE NOBORI2 TRIAL
A Randomized, Prospective, Intercontinental Evaluation of a Bioresorbable Polymer Sirolimus-eluting Stent: the CENTURY II Trial: an Update with 2 Years.
How and why this study may change my practice ?
EVERBIO II Trial design: Patients with CAD were randomized in a 1:1:1 fashion to either Absorb BVS, Biomatrix Flex stent [BES], or Promus Element EES.
Kyoto University Hospital, Japan
3-Year Clinical Outcomes From the RESOLUTE US Study
ENDEAVOR IV: 5 Year Final Outcomes
Comparison of Everolimus- and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds: 2-year Outcomes of the EVERBIO.
BASKET-PROVE II Trial design: Subjects with stable or unstable coronary artery disease undergoing stent implantation were randomized to a biodegradable-polymer.
ZEUS Trial design: Patients who were deemed uncertain DES candidates due to bleeding, thrombotic, or restenosis risk were randomized to receive either.
Potential conflicts of interest
On behalf of all principal COMPARE II investigators:
ENDEAVOR II Five-Year Clinical Follow-up
FOR DISTRIBUTION BY MEDTRONIC OFFICE OF MEDICAL AFFAIRS ONLY.
12-month clinical and 13-month angiographic outcomes from a randomized trial evaluating the Absorb Bioresorbable Vascular Scaffold vs. metallic drug-eluting.
Gregg W. Stone, MD Columbia University Medical Center
ENDEAVOR III Multicenter Randomized Trial Clinical/MACE Angio/IVUS
Long Term Clinical Results from the Endeavor Program: 5-Year Follow up
Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: First Report of the Five-Year Clinical Outcomes from.
Presentation transcript:

Boston Scientific Corporation: DES Bioabsorbable Technologies Keith Dawkins MD FRCP FACC FSCAI Global Chief Medical Officer Executive Vice President Boston Scientific Corporation

Conflicts of Interest Boston Scientific Corporation Employee Stockholder

DES Polymer Considerations Purpose of the Polymer Provides mechanically stable matrix for drug Modulates drug release into vessel wall Polymer has no function after drug release is complete All polymer coatings have potential to be damaged Damaged durable polymers are permanent

Safety Efficacy Potential Issues with Durable Polymer DES Late / very late stent thrombosis Higher risk in certain patient populations Potentially require long-term DAPT Chronic inflammation with neoatherosclerosis Constant irritant may lead to late restenosis Diminished efficacy in diabetic populations

SYNERGY™ Stent: Design Characteristics Element Stent Platform Bioerodable PLGA polymer is only applied to the abluminal surface of the stent Abluminal delivery of Everolimus Maximum abluminal coating thickness 4μm Drug and Polymer gone ~ 3 months Enhanced Stent geometry Reduced Stent Profile Laser-cut hypotube SYNERGY Everolimus PLGA Ultrathin Abluminal, Bioerodable Polymer (Rollcoat Technology) Element Stent

SYNERGY™ Stent Platform Stent Architecture Visibility PROMUS Element™ 81µm PROMUS Element™ SYNERGY™ SYNERGY™ 74µm PROMUS Element & SYNERGY Stent Designs Platinum Chromium (PtCr) Alloy Radial Strength & Visibility Similarities SYNERGY Design Modifications Strut Thickness Connector Angle Peak Radius Additional End Connectors Crimping Profile Flexibility Conformability Longitudinal Robustness Improvements

Comparative Strut Thickness SYNERGY (360 days) Strut Thickness (µm) BVS 150µm BioMatrix Flex 120µm Resolute Integrity 89µm PROMUS Element 81µm XIENCE V 81µm SYNERGY 74µm Thinner struts are associated with more rapid healing

Relative Drug & Polymer Weight // Bare Metal Stent SYNERGY RESOLUTE Integrity BioMatrix Flex XIENCE/PROMUS BVS / / I I I I I I I I I I I 0 100 200 300 400 500 600 700 7,700 7,800 7,900 Coat Weight (µg) per 16 mm Stent

SEM of coating (x5000 magnification) SYNERGY Stent Polymer Coating Microstructure PLGA Polymer Everolimus Drug Stent Strut SEM of coating (x5000 magnification) BSC Internal Data

Time Course for Drug & Polymer Dissolution 3 6 Drug Polymer 6 6 9 10 12 3 Time (Months)

Vascular Response in Healthy Swine Model Similar vascular response to SYNERGY™ & OMEGA™ (BMS) OMEGA™ Stent SYNERGY™ Stent 30 Days 90 Days 180 Days 360 Days Wilson GJ: J Am Coll Cardiol 2011;57:E1661

Cellular Response to Platinum Chrome Platinum Chrome vs. PVDF Less Platelet Adhesion Less Platelet Aggregation More Strut Coverage More mature & functioning Endothelium Inflammatory potential similar between Platinum Chrome & PVDF Garanich JS: J Am Coll Cardiol 2011;58:B126 Tellez A: J Am Coll Cardiol 2012;60:B187

SYNERGY Stent: Clinical Trials EVOLVE FHU First Human Use Trial. 291 patients. PROMUS Element vs. SYNERGY vs. SYNERGY Half-Dose (1:1:1). Primary Endpoint: 6 month Late Loss + Composite Safety @ 30 days Enrolling EVOLVE II Global IDE Trial. 1684 patients, 150 sites, 19 countries . PROMUS Element Plus vs. SYNERGY (1:1) single-blind trial. Primary Endpoint: 12 month TLF EVOLVE II QCA Quantitative Angiography. 100 Patient Registry, 10-15 sites (Australia, Japan, New Zealand, Singapore). Primary Endpoint: 9 month in-stent Late Loss EVOLVE China China regulatory approval trial (SFDA). 400 patients, up to 15 sites. PROMUS Element vs. SYNERGY (1:1) Primary Endpoint: 9 month Late Loss EVOLVE DAPT Prospective, Multi-center, Global, double-blind RCT: 3 months vs. 12 months DAPT. 9000 patients. Primary Endpoint: Cardiac Death/ MI

Late Loss Distribution EVOLVE Trial Results (6 months) Late Loss at 6 months Late Loss Distribution p=0.19 p=0.56 In-Stent Late Loss (mm) Late Loss Distribution (%) PROMUS Element SYNERGY Half-Dose SYNERGY -0.5 0.0 0.5 1.0 1.5 2.0 Non-inferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents Meredith IT: J Am Coll Cardiol 2012;59:1362–1370

EVOLVE Trial Results (6 months) Late Loss at 6 months Safety & Efficacy at 6 months p=0.19 Cardiac Death = 0% (All Groups) Q-MI = 0% (All Groups) Stent Thrombosis = 0% (All groups) p=0.56 Late Loss (mm) Patients (%) PROMUS Element SYNERGY Half-Dose SYNERGY Non-inferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents Meredith IT: J Am Coll Cardiol 2012;59:1362–1370

EVOLVE Trial Results (12 months) PROMUS Element (n=98) SYNERGY Half-Dose (n=99) SYNERGY (n=94) Components of TLF Patients (%) Verheye S: Presented at EuroPCR 2012

EVOLVE II Study Design SYNERGY™ Stent Pivotal Trial 1,954-2,006 patients with atherosclerotic native coronary lesions ≤ 34 mm in length, RVD ≥2.25 mm ≤ 4.0, %DS ≥ 50 Up to 3 lesions in 2 vessels (excludes LM disease, CTO, ISR, STEMI) Randomized Cohort (RCT) Up to 160 global sites PK Substudy PROMUS Element™ Plus Stent N=842 SYNERGY™ Stent N=842 SYNERGY™ Stent N=20-30 RCT Design Multicenter, Noninferiority trial Single-blind, 1:1 randomization Primary Endpoint: TLF (CD, TV-MI, or TLR) at 12 months Follow-up: 30d, 6m, 12m, 18m and annual 2-5 years Diabetes Substudy SYNERGY™ Stent N=250-292

SYNERGY™ vs. BVS SYNERGY™ (BSC) BVS (ABT) Acute Performance +++ ± Strut Thickness Thin (74µm) Thick (150µm) Radial Strength + Fracture Resistance Visualization Ability to Post-Dilate - Full Matrix Low Drug Load Low Polymer Load Short Time to Polymer Dissolution Low Particulates Normal Vessel Function ? Shorter DAPT

The Burden of Stent Thrombosis... Cost Thrombus Hemorrhage DAPT

Relative Cost (DES Stent vs. DAPT) 7.1% 13.3% US Dollars ($) 23.5% 60.6% Assumptions: Cost of Aspirin 81mgs = US$ 0.05 Cost of DES = US$ 1600 (MRG Data, September 2012) Cost of Clopidogrel 75mgs = US$ 2.80 (www.pharmacychecker.com).

Conclusions Long term durable polymer exposure is potentially undesirable The SYNERGY™ Stent is a next generation bioabsorbable polymer technology with unique properties: Polymer gone shortly after drug elution is complete at 3 months Parallel, synchronous drug release and polymer absorption Ultra-thin abluminal coating and lower polymer load than previous technologies Presence of drug in arterial tissue throughout entire course of polymer degradation to promote optimal healing 12-month safety and efficacy data from the EVOLVE Trial support positive clinical performance Bioabsorbable polymer DES may improve late outcomes (reduce late/very late ST), minimize DAPT dependency, and enhance healing vs. durable polymer DES. Further confirmatory trials are ongoing