Bioabsorbable Scaffolds: The Next Holy Grail?

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1 Bioabsorbable Scaffolds: The Next Holy Grail? New Cardiovascular Horizons New Orleans, LA June 06, 2013 Lewis B. Schwartz, M.D., F.A.C.S. Vascular Surgery and Endovascular Therapy University of Chicago

2 Rationale for the Development of Bioresorbable Vascular Scaffolds Limitations of metallic stents restenosis stent thrombosis chronic inflammation imaging artifacts jailed side branches inhibition of positive remodeling (shear stress adaptation) prevention of normal physiologic function such as vasomotion need for prolonged anti-platelet therapy permanent implant complicating repeat intervention Adapted from Waksman R. Update on bioabsorbable stents: From bench to bedside. J Interven Cardiol 2006;19:

3 Igaki-Tamai PLA Stent Stone GW. The Promise of ABSORB Bioabsorbable Vascular Scaffolds. Cardiovascular Revascularization Technologies; 2013 February 25; Washington. 3 Hideo Tamai

Bioresorbable Scaffolds 9-year follow-up

Ten-year follow-up of the IGAKI-TAMAI stent.

4 Bioresorbable Scaffolds 9-year follow-up PRE-PROCEDURE POST-DILATION 9-YEARS Onuma Y, Garg S, IOkamura T, Ligthart J, Jan van Geuns R, de Feyter PJ, et al. Ten-year follow-up of the IGAKI-TAMAI stent. A posthumous tribute to the scientific work of Dr. Hideo Tamai. Euroint. 2009;5 (suppl F):F109-F11.

5 Igaki-Tamai long-term results Nishio S, Kosuga K, Igaki K, Okada M, Kyo E, Tsuji T, et al. Long-term (>10 years) clinical outcomes of first-in-man biodegradable poly-l-lactic acid coronary stents: Igaki-Tamai Stents. Circ. 2012;

Bioresorbable Coronary Scaffolds Reported Clinical Studies Device Study Drug Lesions n

Igaki-Tamai PROGRESS AMS none coronary 63 48% restenosis @ 12-months AMS (Biotronik)

52 mm @ 12-months REVA RESORB 30 67% TLR @ 6-months none coronary RESTORE I 22 2 MACE

coronary 45 2.4% restenosis @ 6-months 56 3.

6 Bioresorbable Coronary Scaffolds Reported Clinical Studies Device Study Drug Lesions n Outcome Igaki-Tamai FIM none coronary 50 18% 12-months 28% 10-years Igaki-Tamai PROGRESS AMS none coronary 63 48% 12-months AMS (Biotronik) BIOSOLVE-I paclitaxel coronary 22 10% 6-months 24 in-scaffold LLL months REVA RESORB 30 67% 6-months none coronary RESTORE I 22 2 ABSORB Cohort A 30 12% 6-months ABSORB Cohort B everolimus coronary % 6-months % 12-months ABSORB (Abbott) ABSORB Extend % 6-months DESolve I novolimus coronary 15 0% DESolve (Elixir)

resorbed, fully metabolized Poly(D,L-lactide) (PDLLA) coating Naturally resorbed, fully metabolized

7 Abbott Vascular Everolimus Eluting Bioresorbable Vascular Scaffold Components Scaffold Coating Drug Delivery system Bioresorbable Bioresorbable Everolimus XIENCE V Poly(L-lactide) (PLLA) Naturally resorbed, fully metabolized Poly(D,L-lactide) (PDLLA) coating Naturally resorbed, fully metabolized Similar dose density and release rate to XIENCE V World-class deliverability Photos taken by and on file at Abbott Vascular.

8 Absorb v. Cypher Absorb 1 month 6 months 1 year 2 years 3 years 4 years Cypher Representative photomicrographs of porcine coronary arteries, 2x Photos taken by and on file at Abbott Vascular. Tests performed by and data on file at Abbott Vascular.

9 BVS Cohort A Degradation on the Bench and in Porcine Coronary Arteries Virmani R. Challenges for the development of biodegradable scaffolds: Insight from the preclinical trials. Cardiovascular Research Technologies; 2013 February 25; Washington.

10 Post-procedure Pre-procedure A B C D E A B C D E

11 A B C D E A B C D E

12 The Lancet 2008;371: lesions Pre-procedure Lesion length (mm) 8.66 RVD (mm) 2.78 MLD (mm) 1.10 DS (%) 59% Post-procedure In-stent MLD (mm) 2.33 In-stent DS (%) 16% In-stent acute gain (mm) mos. follow-up In-stent MLD (mm) 1.88 In-stent DS (%) 27% In-stent late loss (mm) 0.44 ± 0.35 In-stent ABR (%) 11.5%

13 In-stent late loss (mm) Comparison of DES - Late Lumen Loss 4 mos 6 mos 8/9 mos 12 mos CYPHER TAXUS ENDEAVOR XIENCE V

14 ABSORB Cohort A Temporal Lumen Dimensional Changes, Per Treatment Post-PCI n = 25 6 Mos. n = 25 ABSORB Cohort A Scaffold Area MLA = 5.09mm % 3.92mm 2 Late Loss = 0.43 mm Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. The Lancet 2009;373:

ABSORB Cohorts A & B Lower MCUSA (maximum unsupported scaffold area) More even support of arterial wall More uniform strut distribution Lower late stent area loss Improved stent retention Unchanged

15 ABSORB Cohorts A & B Lower MCUSA (maximum unsupported scaffold area) More even support of arterial wall More uniform strut distribution Lower late stent area loss Improved stent retention Unchanged material and strut thickness Onuma Y, Piazza N, Ormison JA, Serruys PW. Everolimus-eluting bioarbsorbable stent - Abbott Vascular programme. Euroint 2009;5(suppl F):F98-F ;373: Gomez-Lara J, Brugaletta S, Diletti R, Garg S, Onuma Y, Gogas BD, et al. A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds. Eur Heart J 2010.

16 Radial Strength Oberhauser JP, Hosseiny S, Rapoza RJ. Design principles and performance of bioresorbable polymeric coronary scaffolds. EuroInt. 2009;5 (suppl F):F15-F22.

A comparative assessment by optical coherence tomography of the performance of the

17 ABSORB Cohorts A & B COHORT A COHORT B 6-mos. Postprocedure Postprocedure 6-mos. Gomez-Lara J, Brugaletta S, Diletti R, Garg S, Onuma Y, Gogas BD, et al. A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds. Eur Heart J 2010.

18 % Patients ABSORB Cohort B: 6-Month QCA Intent to Treat Cumulative Incidence Curve for Late Loss 100% 90% 80% 70% 0.10 ± 0.23 mm 0.85 ± 0.36 mm 60% 0.43 ± 0.37 mm 50% 40% 30% 20% 0.19 ± 0.18 mm BVS Cohort A (N = 26) BVS Cohort B (N = 42) Xience EES* (N = 23) Vision BMS* (N = 27) 10% 0% In-Stent Late-Loss (mm) *SPIRIT First Serruys PW, Onuma Y, Ormiston JA, de Bruyne B, Regar E, Dudek D, et al. Evaluation of the second generation of a bioresorbable everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: Six-month clinical and imaging outcomes. Circ. 2010;122(22): ABSORB is neither approved nor available for sale in the U.S.

19 ABSORB Cohort B two-year results Pre- Absorb Immediately Post Absorb 6 Months 2 Years Ormiston J, Serruys PW. ABSORB Cohort B Trial Two year clinical and angiographic results of the ABSORB everolimus eluting bioresorbable vascular scaffold (poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA.

20 Angiographic late lumen loss two-year results In-stent or scaffold LLL (mm) Taxus (Park) Taxus (ISAR- TEST 2) Cypher (Park) Cypher (ISAR- TEST 2) Cypher (ISAR- TEST 4) Cypher (ISAR- TEST-3) Xience (ISAR TEST 4) Absorb (Cohort B) Byrne RA, Iijima R, Mehilli J, Pinieck S, Bruskina O, Schömig A, et al. Durability of antirestenotic efficacy in drug-eluting stents with and without permanent polymer. J Am Coll Cardiol: Cardiovasc Interv. 2009;2: Byrne RA, Kufner S, Tiroch K, Massberg S, Laugwitz K-L, Birkmeier A, et al. Randomised trial of three rapamycin-eluting stents with different coating strategies for the reduction of coronary restenosis (ISAR-TEST-3): 2-year follow-up results. Heart. 2009;95: Park KW, Kim C-H, Lee H-Y, Kang H-J, Koo B-K, Oh B-H, et al. Does late catch-up exist in drug-eluting stents: Insights from a serial quantitative coronary angiography analysis of sirolimus versus paclitaxel-eluting stents. Am Heart J. 2010;159: Ormiston J, Serruys PW. ABSORB Cohort B Trial Two year clinical and angiographic results of the ABSORB everolimus eluting bioresorbable vascular scaffold (poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA. Byrne RA, Kastrati A, Tiroch K, Massberg S, Wieczorek A, Laugwitz K-L, et al. Two-year outcomes after everolimus- or sirolimus-eluting stents in patients with coronary artery disease in the ISAR-TEST 4 Trial. Transcatheter Cardiovascular Therapeutics; 2010; San Francisco, California.

21 Absorb v. XIENCE V at 2-years MACE (C-Death, MI, ID-TLR) 22% 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% ABSORB BVS(B1+B2) XV (3.0 x 18mm subgroup, SPI+SPII+SPIII RCT) Time Post Index Procedure (Months) 758-day HR 0.97 [0.42,2.21] p= % 7.9% Days Absorb XIENCE V Rapoza R. Absorb BVS Program: Long-term experimental data angiography, IVUS, OCT, histology and micro CT. Local Drug Delivery and Cardiovascular Course on Revascularisation; 2012 February 4; Geneva, Switzerland. ABSORB and XIENCE V are trademarks of the Abbott Group of Companies

22 QCA post procedure Post procedure Preprocedure MLD 2.45mm FUP before vasomotion 5 Min. After Methergine After Nitro Mean LD -0.60mm (-22%) Minimal LD 1.58 mm Mean LD 2.12 mm Mean LD +0.55mm (+26%) Minimal LD 2.32 mm Mean LD 2.67 mm MLD 2.46 mm Mean LD 2.72mm Late Loss: -0.01mm

23 in Vessel Diameter (mm) (pre-drug infusion to post-drug infusion) Vasoconstriction Vasodilation Recovery of Vasoreactivity after Absorb Implantation 1 6 Months 1 12 Months 2 24 Months 3 ABSORB Cohort B1 ABSORB Cohort B2 ABSORB Cohort A 0.5 (n=15) (n=6) (n=19) (n=13) (n=9) (n=7) Acetylcholine -1 Methergine Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington. 1. Adapted from Serruys, PW. ACC Adapted from Serruys, PW. ACC Adapted from Serruys, PW, et al. Lancet 2009; 373:

24 Okamura T, Serruys PW, Regar E. The fate of bioresorbable struts located at a side branch ostium: serial three-dimensional optical coherence tomography assessment. Euroint. 2010; doi: /eurheartj/ehq175; online publish-ahead-of-print 31 May ABSORB Cohort A: 24-Month Results

25 ABSORB Cohort B - Late Lumen Enlargement by IVUS Post-PCI 6 Months 2 Years N = 33 N = 33 N = 33 ABSORB Cohort B Serial Analysis Scaffold Area Lumen Area 6.53 mm 2 1.7% 6.36 mm mm 2 Lumen Area 7.2% Late Loss = 0.19 mm Ormiston J, Serruys PW. ABSORB Cohort B Trial Two year clinical and angiographic results of the ABSORB everolimus eluting bioresorbable vascular scaffold (poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA.

26 ABSORB EXTEND Non-Randomized, Single-Arm, Continued Access Trial Clinical Follow-Up ~1,000 subjects Up to 100 global sites (non-us) Follow-up (months) MSCT follow up (n=100) OCT, IVUS follow up (n=50) Study Objective Continued Access trial. FPI: Jan 11, 2010 Endpoints Treatment Device Sizes Typical PCI clinical endpoints Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions >22 and 28 mm Scaffold diameters: 2.5, 3.0, 3.5 mm Scaffold lengths: 12*, 18, 28 mm Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012 Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

ABSORB EXTEND Non-Randomized, Single-Arm, Continued Access Trial Intent to Treat (ITT) Analysis Interim Snapshot Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250

27 ABSORB EXTEND Non-Randomized, Single-Arm, Continued Access Trial Intent to Treat (ITT) Analysis Interim Snapshot Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012 Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

29 The ABSORB Clinical Trials ABSORB Cohort A n = 30; FIM ABSORB Cohort B n = 101; FIM ABSORB Extend n = up to 1,000 ABSORB II n = ~330 ABSORB PHYSIOLOGY n = ~35 ABSORB FIRST n = 10,000 ABSORB III n = ~1,502 ABSORB Japan n = ~265 ABSORB China n = ~200 5 Y 1 Y 2 Y 3 Y 4 Y 5 Y Enrollment & Follow-Up Enrollment & Follow-Up Enrollment & Follow-Up 1 Y 1 Y Enrollment & Follow-Up Enrollment & Follow-Up 2 Y 3 Y 1 Y 2 Y Enrollment & Follow-Up Enrollment & Follow-Up 2 Y 3 Y 1 Y 1 Y 1 Y 2 Y 1 Y 2 Y 3 Y 2 Y 2 Y Total Absorb Pts Studied n=~599 n~965 n~5,709 n~13,463 n~13,463 n~13,463 Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

30 BVS Implantation Technique Use online QCA Avoid under sizing, as postdilation is limited to 0.5 mm Proper lesion preparation = sufficient large balloon (min 2.5 mm) Use more supportive wires Direct stenting possible in ACS Van Geuns R-J. BVS Expand: First results of wide clinical applications. Cardiovascular Research Technologies; 2013 February 25; Washington.

Bioresorbable Scaffolds - Ongoing Clinical Studies Device Company Study Drug Lesions n Status DREAMS AMS Biotronik BIOSOLVE I paclitaxel coronary 56 in-scaffold LLL 0.

31 Bioresorbable Scaffolds - Ongoing Clinical Studies Device Company Study Drug Lesions n Status DREAMS AMS Biotronik BIOSOLVE I paclitaxel coronary 56 in-scaffold LLL months ReZOLVE Reva Medical, Inc. RESTORE I none coronary 22 2 months RESTORE II sirolimus 125 enrolling ABSORB EXTEND 1000 enrolling Abbott everolimus coronary ABSORB ABSORB III 2000 enrolling Elixir Medical DESolve I novolimus coronary 16 in-scaffold LLL 0.19 months DESolve DESolve Nx 126 enrolled

$polymer reactions Avoidance/resolution of positive remodeling and stent malapposition Avoidance/resolution of late strut fractures Less neoatherosclerosis Un-jailing of side-branches Plaque$

32 The Resorbable Holy Grail Restoration of normal vasomotion, with NO production Restoration of normal shear stress and cyclic strain Restoration of normal vessel curvature Reduced risk of very late polymer reactions Avoidance/resolution of positive remodeling and stent malapposition Avoidance/resolution of late strut fractures Less neoatherosclerosis Un-jailing of side-branches Plaque regression MRI/CT imaging follow-up The return of normal vessel architecture Stone GW. The Promise of ABSORB Bioabsorbable Vascular Scaffolds. Cardiovascular Revascularization Technologies; 2013 February 25; Washington.

Best Strategy is Still Out There: Bioresorbable Vascular Scaffold (BVS) and New Technology?

Best Strategy is Still Out There: Bioresorbable Vascular Scaffold (BVS) and New Technology? ARCH St. Louis Craig M. Walker, MD, FACC, FACP Clinical Professor of Medicine Tulane University School of Medicine