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Update on the Development of BVS: Challenges for the Development of Polymeric Biodegradable Scaffolds for Peripheral Vascular Intervention Richard Rapoza February 25, 2013 Richard J. Rapoza, PhD Full-time employee of Abbott Vascular Clinical Goals of Minimally Invasive SFA Treatment • Acute Outcomes – Re-establish flow with a uniform vessel appearance – Minimize acute vessel closure and recoil or geometrical disturbance • Long Term Outcomes – Sustain Patency (hyperplasia, constrictive remodeling) – Minimize long term thrombosis risk – Permit future re-treatment ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 3 Multiple Approaches • Angioplasty – POBA – Drug Coated Balloons • Atherectomy • Balloon Expandable Stents • Self-Expanding Stents (SES) – Bare Metal Stents – Drug Eluting Stents – Covered Stents • Bioresorbable Vascular Scaffolding (BVS) – Bare BVS – Drug Eluting BVS* * Drug Eluting BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 4 The SFA Applies Dynamic Forces SFA Challenges Shortening 18 mm Increased Curvature 0.04 cm Twist 46 degrees Flexion Points (>15 degrees) 2/10 Klein et al. Catheter Cardiovasc Interv 2009;74:799. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 5 Lesion Length Impacts Primary Patency Regardless of Treatment Modality Worse results in long SFA lesions … Good results in short lesions with SES, DCB, and DES… Adapted from Shroë H. Superficial Femoral Artery PTA or Stenting 5 year results. CIRSE 2011. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 6 High Chronic Outward Force Leads to Chronic Stent-Vessel Irritation Sizing Example Optimal Oversizing 8 mm stent compressed to: 7.3 – 6.2 mm Stent Medium Oversizing High Oversizing 6.2 – 5.0 mm 5.0 – 4.2 mm Stent Stent Note: Preclinical animal models. Zhao HQ et. al. Cardiovasc Intervent Radiol 2009;32: 720-726. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 7 Preliminary DES Studies Primary Patency Drug Eluting Stents vs. Bare Metal Stents VIENNA vs. STRIDES vs. SIROCCO Adapted from Lammer J. First In-man Clinical Trial of an self expandable Everolimus-coated Stent in the SFA. ISET 2010. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 8 Recent DES Data Freedom from TLR After 5 Years Stent Type Everflex™ 323 Zilver® PTX® 216 Astron® 111 Astron® Pulsar® 95 Lifestent® 51 S.M.A.R.T.® 13 Luminexx® 12 Complete® SE Ave. Lesion Length = 15494 mm n Total 6 827 Bosiers M. 5-year evaluation of SFA stenting (Belgian/German study). VEITH 2012. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 9 Post Drug Elution, Chronic Irritation Remains 6 mm stents deployed at 6 mm and compressed to 3 mm Model with Leg Motion and Blood Pressure Test(s) performed by and data on file at Abbott Vascular. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 10 Clinical Impact of SFA Treatment Modalities Best Preferred Solution Metallic Stents Drug Eluting BVS Acute Outcome Atherectomy DCB PTA Worst Best Long-Term Outcome BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 11 Drug Eluting BVS Bioresorbable Scaffold • Poly(L-lactide) (PLLA) • Naturally resorbed, fully metabolized • Designed for SFA and iliac arteries Bioresorbable Coating • Poly(D,L-lactide) (PDLLA) coating • Naturally resorbed, fully metabolized Everolimus • 100 μg/cm2 Delivery System • Balloonexpandable delivery system • 035” OTW platform BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. All illustrations are artists’ renditions. Illustrations created by Abbott. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 12 Drug Eluting BVS Phases of Functionality Revascularization Restoration Stabilize Disappear Mass Support Drug Elution • Lumen stabilization and scaffold disappearance are the key ingredients for a durable SFA therapy. • Combining endovascular legacy with deep coronary BVS experience creates a specialized platform to address long term SFA needs BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 13 Vascular Response to BVS at 2, 3, 4 Years Arterial Integration and Accommodation • Mass loss data suggests 100% BVSof material mass has been lost within 2 - 3 years 324 years years • The shape of struts is still apparent at 2 years, although the device is fully resorbed • No inflammation around the 1 year pre-existing strut regions 2 years 3 years 4 years • 3 years: struts fully replaced by tissue of10x pre-existing • 4 years: sites struts are indiscernible Alcian Blue Stain: Proteoglycan Representative photomicrographs of porcine coronary arteries, 2x Cypher BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. Photos taken by and on file at Abbott Vascular. Tests performed by and data on file at Abbott Vascular. Representative preclinical data from porcine coronary arteries, 2x objective. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 14 Chronic Deformation Effects on Neointima Leg flexion causes stent deformation and neointimal formation Test(s) performed by and data on file at Abbott Vascular. Healthy porcine iliofemoral artery at 12 months. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 15 BVS Technically Designed for Physiological Needs and Clinical Goals Clinical goals drive the scaffold design, as governed by the relationship between scaffold function and physiological need Clinical Goal • Re-establish laminar flow with a uniform angiographic appearance • Restore natural vessel function • Establish durable result while permitting potential for future re-treatment Physiological Need Scaffold Function • Minimize acute vessel closure and recoil or geometrical disturbance to the vessel • Support vessel until stabilized, then allow unconstrained vessel movement • Prevent long term vessel damage from persistent irritation and/or chronic outward force • Acutely provide radial support • Form a vessel:scaffold composite and develop predictable discontinuities • Naturally resorb, fully metabolize Serruys PW, Onuma Y, Ormiston JA, et al. Circulation. 2010;122(22):2301-2312. Ormiston JA, Serruys PW, Onuma Y, et al. Circ. Cardiovasc. Interv. 2012;5(5):620-632. BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 16 Crush Recovery Comparison Balloon Expandable Stent vs. Balloon Expandable BVS BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. This video demonstrates the physical properties and capabilities of PLLA-based bioresorbable scaffolds. Tests performed by and data on file at Abbott Vascular. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 17 Designed Loss of Continuity Basic design concept: rings joined by links Link Ring • Design decouples radial support and axial flexibility – Rings provide resistance to radial loads – Links provide flexibility to navigate tortuous paths and conformability to match vessel curvature • It is acceptable for links become discontinuous prior to rings, because they are not necessary for support BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. Photos taken by and on file at Abbott Vascular. Tests performed by and data on file at Abbott Vascular. All illustrations are artists’ renditions. Illustrations created by Abbott. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 18 ESPRIT I Trial Design A single de novo lesion in the superficial femoral (SFA) or iliac arteries in patients with symptomatic claudication (Rutherford Becker Category 1-3) • Prospective, Single Arm, Multi-Center OUS trial evaluating the Esprit BVS (N=35) • One target lesion treated with a single 6.0 x 58 mm Esprit BVS • Vessel diameter from ≥ 5.5 – ≤ 6.5 mm, segment length ≤ 50 mm Baseline 1 mo 6 mo 12 mo 2 yr 3 yr Clinical, Duplex (all subjects) Angiography (all subjects) IVUS Substudy (N ~ 10) MSCT/ MR Substudies (N ~ 5 each) PK Sub Study (N ~ 10, out to 1 mo.) Trial Objective: Evaluate safety and performance of the Esprit BVS in subjects with symptomatic atherosclerotic disease of the SFA or iliac arteries Endpoints: Procedural, clinical, functional, hemodynamic, angiographic, IVUS, non-invasive imaging in-hospital and at F/U time points indicated www.clinicaltrials.gov BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 19 ESPRIT I Lesion Characteristics ESPRIT (N=35) External Iliac (%) SFA (%) 11.4 84.0: Proximal 14.3 Mid 31.4 Distal 54.3 Target lesion length (mm) Total occlusions (%) Occlusion length (mm) 35.49 ± 15.74 28.0 30.6 ± 15.7 Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course 2013. BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 20 ESPRIT I Angiographic Results (Core Lab) Pre-Procedure (N=35) Post-Procedure (N=35) Lesion length (mm) 35.49 --- In-segment RVD (mm) 4.85 4.91 In-segment MLD (mm) 1.01 4.25 Diameter Stenosis (%) 80.04 ± 15.14 13.07 ± 7.52 80.99, (42.1, 100.0) 10.98, (2.63, 29.86) Median, (min, max) Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course 2013. BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 21 ESPRIT I Key Study Endpoints ESPRIT (N=34) 1-Month Deaths 0.0% Any amputation of treated limb 0.0% Bypass surgery of treated limb 0.0% Scaffold thrombosis 0.0% Target lesion revascularization (TLR) 0.0% Target vessel revascularization (TVR) 0.0% Target extremity revascularization (TER) 0.0% Binary restenosis 0.0% •One subject withdrew consent for further follow-up. Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course 2013. BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 22 ESPRIT I Rutherford Becker Class and Ankle Brachial Index ESPRIT baseline (N=35) ESPRIT 1-month (N=34*) 0% 84.8 % Rutherford 1 (mild claudication) 8.6 % 12.1 % Rutherford 2 (moderate claudication) 34.3 % 3.0 % Rutherford 3 (severe claudication) 57.1 % 0 0.75 ± 0.14 0.74, (0.45, 1.00) 1.00 ± 0.11 1.0 (0.45, 1.00) Rutherford 0 (no claudication) ABI Median, (min, max) Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course 2013. BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 23 Conclusions • Self expanding metallic stents can impart chronic injury through oversizing / chronic outward force and local strut/cell movement • Drug elution is effective only while present in tissue. Once elution ceases, and drug is metabolized, chronic injury will continue unmasked. • Fully resorbable scaffolds have the potential to pave effectively after intervention to: – Sustain lumen dimensions while vessel wall heals – Disappear mechanically and not cause chronic injury – Fully resorb to restore mechanical integrity to the vessel wall BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 24 Abbott Vascular 3200 Lakeside Dr., Santa Clara, CA. 95054 USA, Tel: 1.800.227.9902 Tests performed by and data on file at Abbott Vascular. All illustrations included are artist’s renditions. Not drawn to scale. All photos taken by and on file at Abbott Vascular. BVS for the peripheral anatomies is an investigational device outside the United States. ESPRIT I is an Abbott sponsored clinical trial outside the United States. Astron and Astron Pulsar are trademarks of Biotronik SE & Co. KG. Lifestent and Luminexx are trademarks of C. R. Bard. Zilver and Zilver PTX are trademarks of Cook Medical. Everflex is a trademark of Covidien. S.M.A.R.T. is a trademark of the Cordis Corporation, a Johnson & Johnson company. Complete SE is a trademark of Medtronic, Inc. www.AbbottVascular.com ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 02/13 ©2013 Abbott. All rights reserved. AP2938192-US Rev. A 25