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