Taking DES technology from concept to long term clinical evidence. Aurore Bouvier Global Product Manager Biosensors Europe

Transcription

1 Taking DES technology from concept to long term clinical evidence Aurore Bouvier Global Product Manager Biosensors Europe

2 My conflicts of interest are: Full time employee of Biosensors Europe SA

3 BA9 shows sustained safety and efficacy independent from stent platform or method of drug delivery! BioMatrix TM BioMatrix TM Flex BioFreedom TM TM Nobori AXXESS (Terumo) Custom NXTM (XTENT) Stainless Steel Balloonexpandable Abluminal biodegradable polymer Stainless Steel Balloonexpandable Polymer Free Nitinol Self-expandable Abluminal biodegradable polymer SS BA9/PLA Cobalt-Chrome BA9/PLA Designed for Bifurcations

4 Biosensors DES program

5 EN Rev.01 Biolimus A9 PROPRIETARY BA9 DRUG A rapamycin derivative developed specifically for stent application by Biosensors International Effective immunosuppressive and anti-proliferative properties Reduced systemic exposure and more localized drug effect due to highest lipophilicity and abluminal coating 1 1 LIPOPHILICITY COMPARISON Highest lipophilicity of the common limus drugs 1 Minimizes systemic exposure and reduces the drug circulating in the bloodstream Due to high lipophilicity, the drug is rapidly absorbed by tissue 1 Data on file at Biosensors Intl

6 Biolimus is a semi-synthetic sirolimus analogue with 10x higher lipophilicity and similar potency as sirolimus. Biolimus is immersed at a concentration of 15.6 g/mm into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface by a fully automated process. Biolimus is co-released with polylactic acid and completely desolves into carbon dioxide and water after a 6-9 months period. The stainless steel stent platform has a strut thickness of 120 m with a quadrature link design.

7 The Axxess TM Stent Dedicated bifurcation drug-eluting stent Nitinol self expanding stent Abluminal biodegradable PLA/BA9 coating technology 2 models: bifurcation and left main * 4 references for the bifurcation model: 3.0 and 3.5 mm in diameter 11 and 14 mm in length Clinical programs AXXESS Plus and DIVERGE for de novo bifurcations lesions AXXENT for left main lesions Axxess bifurcation drug-eluting stent is CE approved * Left main stent in not CE approved

8 BioFreedom Selectively micro-structured surface holds drug in abluminal surface structures Hypothesis: Polymer-free drug release via porous-eluting stents may reduce late events caused by polymer stent coatings. Potential advantage Avoid long term late adverse effects that might be attributable to the polymer Proprietary Highly Lipophilic Limus drug Improved surface integrity since there is no polymer to be sheared or peeled away from the stent struts Possible shorter need of dual antiplatelet therapy

9 Biosensors DES program

10 LEADERS all-comers Trial Design Stable and ACS Patients Undergoing PCI Assessor-blind 1:1 Randomisation N=1700 Patients 10 European centers BioMatrix Flex (BES)* N=850 Cypher Select (SES) N=850 1:3 Randomisation Clinical F/U N=640 Angio F/U N=210 Clinical F/U N=640 Angio F/U N=210 1 o endpoint: MACE: Cardiac death, MI, clinically-indicated TVR (9 mo) 2 o endpoints: Death, CV death, MI, TLR, TVR Stent thrombosis according to ARC Angiographic study: In-stent % diameter stenosis (9 mo) Late loss, binary restenosis DAPT recommended for 12 months

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12 MACE P non-inferiority < P superiority = Number at risk SES BES MACE = cardiac death, MI, or clinically-indicated TVR * p-value for superiority Serruys et al., oral abstract presentation, TCT 2012

13 Definite ST Landmark 1 Year 6 5 BES SES 0 to 1 year RR 0.99 ( ) P=0.98* 1 to 5 year RR 0.26 ( ) P=0.003* 4 % % 2.0 % 2.5 % % Months P for interaction = * p-value for superiority Serruys et al., oral abstract presentation, TCT 2012

14 % % % % Definite ST in Complex Patients STEMI High SYNTAX SCORE (>16) BES SES 8.1% Δ 5.1% 3.0% 8.1% Δ 4.3% 3.8% 3-year HR 0.45 [0.16 to 1.31] P = 0.14* 8.1% Δ 4.3% 3.8% % 2.6% 2.6% 5.1% 3-year HR 0.50 [0.18 to 1.34] P = 0.16* 5.1% Δ2.0% Δ3.5% Δ3.5% 2.6% Months Months 6.0 Bifurcation 3-year HR 0.46 [0.16 to 1.35] P = 0.15* 6.0 Multi Vessel 3-year HR 0.28 [0.08 to 1.03] P = 0.04* % % 5.2% % Δ0.5% 2.0% 3.8% Δ1.8% 2.0% Δ2.3% 2.0% % Δ1.9% 1.5% Δ3.7% 1.5% Δ3.7% 1.5% Months *P values for superiority Windecker, S., oral presentation,tct Months

15 ASA Ticagrelor Ticagrelor ASA Clopidogrel GLOBAL LEADERS All-Comers PCI Population ACS and Elective/Stable Patients N = Biolimus-eluting stent (BES) BioMatrix Flex 1:1 Randomization, Open-Label Design Study Treatment Strategy Reference Treatment Strategy 1 month ASA + Ticagrelor 23-months monotherapy Ticagrelor 12 months DAPT ACS pts (ASA + Ticagrelor) Elective pts (ASA + Clopidogrel) 12-months monotherapy ASA Primary endpoint: Study Treatment strategy superior to reference treatment strategy on cumulative 2 year composite of all cause mortality and new Q-wave MI

16 9 Month Restenosis in DIVERGE Any In-segment bifurcation restenosis: 6.4% (9/140 at 9 months) 1,2 Parent Vessel RS 3 pts 2 pts Both Side Branch RS 4 pts Location Analysis: Proximal edge: 2.8% 2 SB stent: 4.8% 1,2 (105 SB stents) Very low restenosis rate in bifurcation lesions. AXXESS: 0.7% 1,2 1. Verheye S. et al, J Am Coll Cardiol, Verheye S. et al, oral presentation, TCT 2009 Distal PV Cypher: 2.1% 2

17 % % Long Term Clinical FU available MACE* AXXESS PLUS 5 Years DIVERGE 4 Years Months *(Cardiac death, MI, bypass, ci-tlr) Grube, TCT Months *(all death, MI, id-tlr) Ormiston, EuroPCR 2012

18 COBRA Study Randomized (1:1), multi-center physician initiated trial Axxess (prox. MB) + BioMatrix n=20 Clinical follow-up Angiographic / OCT follow-up True bifurcation with involvement of a significant side branch requiring a stent 2 sites in Belgium (Leuven and Genk) P.I: C. Dubois Dr. C.Dubois and Prof. J.Dens are previous investigator of the DIVERGE trial Xience PRIME using culotte technique n=20 9 mo 12 mo 2 yr 3 yr 4 yr 5 yr 1 Endpoint: stent strut coverage assessed with OCT at 9 months. 2 Endpoints: stent strut apposition and neointimal hyperplasia assessed with OCT at 9 months, angiographic restenosis, Major Adverse Cardiac Events (MACE) and components, stent thrombosis, etc

19 BioFreedom FIM Design First Cohort BioFreedom FIM 182 patients Second Cohort 4 Month Angio FU 75 patients Angio FU 92% Angio FU 92% 12 Month Angio FU 107 patients BioFreedom standard dose (BFD SD) N=25 BioFreedom low dose (BFD LD) N=26 TAXUS Liberté N=24 BioFreedom standard dose (BFD SD) N=35 BioFreedom low dose (BFD LD) N=36 TAXUS Liberté N=36 Enrollment Period Sept 2008 Jan 2009 Enrollment Period Jan 2009 Jun 2009

20 (mm) In-Stent LLL at 12 Months FU 2 nd Cohort PRIMARY ENDPOINT 0.4 P = 0.001* (p=0.11**) P = 0.21* (p=0.55**) 0.35 [0.22, 0.57] [0.09, 0.39] 0.22 [0.17, 0.66] BFD SD BFD LD TAXUS N = 31 N = 35 N = 31 *Non-inferiority tests based on the mean. **Superiority tests. All values are presented as median [IQR]. Grube E., oral presentation, TCT 2010

21 36-Month Outcomes All patients 1 st and 2 nd Cohorts (96.1%) EVENT BFD SD N = 60 BFD LD N = 62 TAXUS N = 60 MACE (All Death, MI, Emergent Bypass or TLR) 7(11.9%) 11(18.1%) 6(10.0%) All Death 3(5.1%) 2(3.3%) 1(1.7%) MI 1(1.7%) 2(3.4%) 1(1.7%) Q Wave MI 0(0.0%) 0(0.0%) 0(0.0%) Non-Q Wave MI 1(1.7%) 2(3.4%) 1(1.7%) Emergent Bypass 0(0.0%) 0(0.0%) 0(0.0%) TLR 3(5.2%) 8(13.2%) 4(6.7%) Definite/probable stent thrombosis (ARC) 0(0.0%) 0(0.0%) 0(0.0%) All P values are non-significant. Tests were performed for BFD SD vs. TAXUS and BFD LD vs. TAXUS. Grube TCT 2012

22 LEADERS FREE Trial Design Prospective, multi-center, multi-national, double blinded randomized trial High Bleeding Risk PCI population (ACS + Elective stable patients) 2500 patients in 60 centers worldwide BioFreedom DCS 1:1 randomization Gazelle BMS Clinical Follow-Up 1 mo 2 mo 4 mo 1 yr 2 yr Primary safety endpoint: Primary efficacy endpoint: Composite of cardiac death, MI, definite/probable stent thrombosis at 1 year (Non-inferiority) Clinically driven TLR at 1 year (Superiority) DAPT mandated for 1 month only, followed by long term SAPT

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