Abbott Vascular BVS Program - ABSORB - A Fully Bioresorbable Vascular

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Abbott Vascular BVS Program - ABSORB - A Fully Bioresorbable Vascular

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The Abbott Vascular BVS ProgramA Fully Bioresorbable Vascular Scaffold : 

The Abbott Vascular BVS ProgramA Fully Bioresorbable Vascular Scaffold

Slide 2: 

Restoration of natural physiologic vasomotor function in some patients Elimination of chronic sources of vessel irritation and sources for chronic inflammation Possibly avoid current challenges with leaving a metal implant behind Potentially reduce the need for prolonged DAPT No permanent implant to complicate future interventions and re-interventions, particularly in younger patients Non-invasive imaging with MSCT or MRA without ‘blooming artifact’ *Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA. Rationale: Vessel scaffolding is only needed transiently* Goal: Revascularize the vessel like a metallic DES, then resorb naturally into the body. Potential benefits: Bioresorbable Scaffold – Rationale and Goals

Abbott Vascular Everolimus-Eluting Bioresorbable Vascular Scaffold Components : 

Abbott Vascular Everolimus-Eluting Bioresorbable Vascular Scaffold Components Bioresorbable Coating Polylactide (PDLLA) coating Fully biodegradable Similar dose density and release rate to XIENCE V Everolimus Polylactide (PLLA) Naturally resorbed, fully metabolized Bioresorbable Scaffold ML VISION Delivery System Seven generations of MULTI-LINK success World-class deliverability All illustrations are artists’ renditions

Bioresorbable Polymer : 

Bioresorbable Polymer Everolimus/PDLLA Matrix Coating Thin coating layer Amorphous (non-crystalline) 1:1 ratio of Everolimus/PLA matrix Conformal Coating, 2-4 m thick Controlled drug release PLLA Scaffold Highly crystalline Provides device integrity Processed for increased radial strength Polymer backbone Drug/polymer matrix

Polylactide Degradation by Hydrolysis : 

Polylactide Degradation by Hydrolysis Primary mode of degradation is by hydrolysis of ester bonds Water preferentially penetrates amorphous regions of the polymer matrix Hydrolysis initially results in a loss of molecular weight, but not radial strength, as the strength comes from crystalline domains Once crystalline domains are hydrolyzed, there is mass loss 1Pietrzak WS, et al. J. Craniofaxial Surg, 1997; 2: 92-96. Middleton JC, Tipton AJ, Biomaterials, 21 (2000) 2335-2346.

Polylactide Degradation & Lactate Metabolism : 

Polylactide Degradation & Lactate Metabolism

Porcine Coronary Artery:Representative Photomicrographs (2x) : 

Porcine Coronary Artery:Representative Photomicrographs (2x) BVS Cohort A CYPHER Photos taken by and on file at Abbott Vascular. 2 years 1 month 6 months 1 year 3 years 1 month 6 months 1 year 2 years 3 years 4 years 4 years Tests performed by and data on file at Abbott Vascular.

Vascular Response to BVS at 2, 3 & 4 years:Arterial Integration and Accommodation : 

Mass loss data suggests 100% of material mass has been lost at 2 years The shape of struts is still apparent at 2 years, although the device is fully resorbed No inflammation around the pre-existing strut regions Vascular Response to BVS at 2, 3 & 4 years:Arterial Integration and Accommodation Tests performed by and data on file at Abbott Vascular. 3 years: struts fully replaced by tissue Photos taken by and on file at Abbott Vascular. Representative porcine coronary arteries, 2x objective

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular Restoration Therapy’? : 

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular Restoration Therapy’? 1 3 6 2 Yrs Mos Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758. Oberhauser JP, et al., EuroIntervention Suppl. 2009; 5: F15-F22.

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular Restoration Therapy’? : 

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular Restoration Therapy’?

Radial Strength : 

Radial Strength Tests performed by and data on file at Abbott Vascular. *Agrawal, et al., Biomaterials 1992 XIENCE V 3.0 mm Radial strength comparable to metal stent at T=0 After Post-Dilatation to 3.5 mm

Slide 12: 

What is the Minimum Duration of Radial Support? Serruys PW, et al., Circulation 1988; 77: 361. n = 342 patients (n = 93 at 30-day F/U; n = 79 at 60-day F/U; n = 82 at 90-day F/U; n = 88 at 120-day F/U) The lumen appears to stabilize approximately three months after PTCA. p < 0.00001 p < 0.00001 Quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months

Radial Strength Over Time : 

Radial Strength Over Time Tests performed by and data on file at Abbott Vascular – in-vitro degradation testing (soaked at 37° C PBS). Duration of Luminal Support – Cohort B 3 Month Minimum Goal

Importance of Respecting Natural Vessel Curvature : 

Importance of Respecting Natural Vessel Curvature Long-term flow disturbances and chronic irritation can contribute to adverse events Gyöngyösi, M. et al. J Am Coll Cardiol. 2000;35:1580-1589. Wentzel, J. et al. J Biomech. 2000;33:1287-1295. 91° 88° Stiff Metal Stents BVS (Cohort B case) Pre BVS Post BVS Serruys, P. , TCT 2009 BVS appears to maintain natural vessel curvature at implantation; long-term, scaffold is fully resorbed

Potential for Mechanical Conditioning : 

Potential for Mechanical Conditioning Gradual disappearance of supportive scaffold Vessel recovers the ability to respond to physiologic stimuli Shear stress & pulsatility Tissue adaptation Structure and functionality Mechanical conditioning may lead to improved cellular organization and vascular function ‘Vascular Restoration Therapy’ Design Goals:

Mechanical Conditioning in Pre-Clinical Model (Porcine) : 

Mechanical Conditioning in Pre-Clinical Model (Porcine) Tests were performed by and data are on file at Abbott Vascular. At 36 months, SMCs are well organized and have undergone transformation to a functional, contractile phenotype Mechanical conditioning

Slide 17: 

Cohort A: 30 patients enrolled March – July 2006 First In Man Clinical Trial Cohort B: 101 patients enrolled March – November 2009

ABSORB Cohort A : 

ABSORB Cohort A N = 30; 6 sites* (Europe, New Zealand) Clinical follow-up schedule: 30 days, 6 months, 12 months, annually to 5 years Imaging schedule: QCA, IVUS, OCT, IVUS VH Baseline 6 18 24 Months Months Months MSCT (optional) *Patients were enrolled in only 4 of 6 sites Derived from Serruys, PW., AHA 2009.

ABSORB Cohort AClinical Study Overall Population : 

ABSORB Cohort AClinical Study Overall Population 30 patients 26 patients QCA n = 4 excluded in Per Treatment Population (3 received non-BVS stent, 1 device failure) n = 1 missed F/U visits* 30 patients clinical 6-month follow-up 19 patients QCA/IVUS 29 patients clinical 2 & 3-year follow-up n = 1 missed F/U visits* n = 1 non-cardiac death** n = 5 refused angiography Intent to treat Per treatment 2-year follow-up Serruys, PW., AHA 2009.

ABSORB Cohort A Clinical Results –Intent to treat : 

ABSORB Cohort A Clinical Results –Intent to treat No new MACE between 6 and 36 months Serruys, PW., AHA 2009. No thrombosis up to 3 years (only one patient on clopidogrel) *One patient withdrew consent and missed the 9, 12, 18 month and 2 and 3 year visits but the vital status of the patient and absence of cardiac event is known through the referring physician. **This patient also underwent a TLR, not qualified as ID-TLR (DS = 42%) followed by post-procedural troponin qualified as non-Q MI and died from his Hodgkin’s disease at 888 days post-procedure.

ABSORB Cohort A OCT Images – Baseline, 6 months and 2 years : 

ABSORB Cohort A OCT Images – Baseline, 6 months and 2 years Struts Side branch Neointimal bridge Serruys, PW., ESC 2008.

Slide 22: 

Baseline M2 1.0 mm/s 6 Month Follow Up M3 1.0 mm/s 2 Year Follow Up C7 20 mm/s Serruys, PW., CCT 2010. ABSORB Cohort A Side Branch Preservation by Angio, OFDI and OCT

ABSORB Cohort ATemporal Lumen Dimensional Changes, Per Treatment : 

ABSORB Cohort ATemporal Lumen Dimensional Changes, Per Treatment ABSORB Cohort A Scaffold Area  11.8%  17.2% Post-PCI 6 Mos. 24 Mos. n = 25 MLA = 5.09mm2 3.92mm2 4.34mm2 Late lumen loss at 6 months mainly due to reduction in scaffold area Very late lumen enlargement noted from 6 months to 2 years n = 25 n = 19 Serruys, PW, et al. Lancet 2009; 373: 897-910.

ABSORB Cohort A Vasomotor Function Testing at 2 Years : 

ABSORB Cohort A Vasomotor Function Testing at 2 Years Serruys, PW, et al. Lancet 2009; 373: 897-910. The reappearance of vasomotion in the proximal, distal, as well as treated segments in response to methergin or acetylcholine suggests that vessel vasoreactivity has been restored and that a physiological response to vasoactive stimulus might occur anew.

BVS Device Optimization Objectives : 

BVS Device Optimization Objectives Cohort A Cohort B Photos taken by and on file at Abbott Vascular. More uniform strut distribution More even support of arterial wall Lower late scaffold area loss Maintain radial strength for at least 3 months Storage at room temperature Improved device retention Unchanged: Material, coating and backbone Strut thickness Drug release profile Total degradation Time

ABSORB Cohort B Clinical Study Design : 

ABSORB Cohort B Clinical Study Design Sponsor: Abbott Vascular Primary Investigators: PW Serruys MD, PhD J Ormiston MD DSMB: J Tijssen PhD, M Wiemer MD, P Urban MD CEC: C Hanet MD, R Tölg MD, V Umans MD Angiographic and IVUS Corelab: Cardialysis (Rotterdam, NL) Prospective, open label, FIM 3.0 x 18mm devices to treat lesion ≤ 14mm in length 12 sites Europe, Australia, New Zealand 101 patients enrolled between 19 March and 6 November 2009 Group 1: 45 patients with imaging FUP at 180 days and 2 years Group 2: 56 patients with imaging FUP at 1 year and 2 years

ABSORB Cohort B : 

ABSORB Cohort B N = 101; 12 sites (Europe, Australia, New Zealand) Clinical follow-up schedule: 30 days, 6 months, 12 months, annually to 5 years Imaging schedule: QCA, IVUS, OCT, IVUS VH Group 1 (n = 45) Group 2 (n = 56) Baseline 6 12 24 Months Months Months 18 Months MSCT (optional)

ABSORB Cohort B Clinical Sites : 

ABSORB Cohort B Clinical Sites Netherlands (3): P. Serruys J. Koolen P. Smits Poland (1): D. Dudek France (1): B. Chevalier Belgium (1): B. de Bruyne Denmark (1): L. Thuesen Switzerland (1): S. Windecker New Zealand (2): J. Ormiston D. McClean Australia (2): I. Meredith R. Whitbourn 12 Clinical Investigative Sites (Europe, New Zealand, Australia)

ABSORB Cohort BClinical/QCA/IVUS Patient Inclusion (Group 1) : 

ABSORB Cohort BClinical/QCA/IVUS Patient Inclusion (Group 1) Serruys, PW., PCR 2010. 45 patients 42 patients 6 months Clinical 6 months QCA 40 patients n = 1, IVUS could not reach the lesion n = 1, no continuous pullback 6 months IVUS 45 patients n = 3, ANGIO/IVUS not done

ABSORB Cohort BBaseline Demographics (Group 1) : 

ABSORB Cohort BBaseline Demographics (Group 1) DeBruyne, B., PCR 2010.

ABSORB Cohort BBaseline Lesion Characteristics/Acute Success : 

ABSORB Cohort BBaseline Lesion Characteristics/Acute Success Clinical Device Success = Successful delivery & deployment of the BVS at intended target lesion & successful withdrawal of the BVS delivery system w/ attainment of final residual stenosis of less than 50% of the target lesion by QCA (by visual estimation if QCA unavailable). Standard pre-dilation catheters & post-dilatation catheters (if applicable) may be used. Bailout patients will be included as device success only if the above criteria for clinical device are met. Clinical Procedure Success = Same as definition above and/or using any adjunctive device without occurrence of ischemia driven major adverse cardiac event (MACE) during the hospital stay w/ a maximum of first seven days post index procedure. DeBruyne, B., PCR 2010. Group 1

ABSORB Cohort B Clinical Results - Intent to treat (Group 1) : 

ABSORB Cohort B Clinical Results - Intent to treat (Group 1) No thrombosis by ARC or Protocol Non-Hierarchical Cardiac Death (%) Myocardial Infarction n (%) Q-wave MI Non Q-wave MI Ischemia Driven TLR n (%) PCI CABG Hierarchical MACE n (%) Hierarchical TLF n (%) 30 Days 6 Months N = 45 N = 45 0 0 0 0 1 (2.2) 1 (2.2) 1 (2.2) 0 1 (2.2) 0 0 0 1 (2.2) 2 (4.4) 1 (2.2) 2 (4.4) MACE: cardiac death, MI, ischemia-driven TLR TLF: cardiac death, MI, ischemmia-driven TLR, ischemia-driven TVR Ormiston, J., TCT 2010. 1 (2.2) 1 (2.2) 9 Months N = 45 0 0 1 (2.2) 1 (2.2) 1 (2.2) 0 2 (4.4) 2 (4.4) 1 (2.2)

ABSORB Cohort BAngiographic Results (Group 1) : 

ABSORB Cohort BAngiographic Results (Group 1) *N = 44 Lesions **N = 42 Lesions DeBruyne, B., PCR 2010.

ABSORB Cohort B 6-Month QCA – Intent to Treat (Group 1) : 

ABSORB Cohort B 6-Month QCA – Intent to Treat (Group 1) DeBruyne, B., PCR 2010.

Slide 35: 

Serruys, PW., PCR 2010. ABSORB Cohort BIVUS Results (Group 1)

ABSORB Cohort BIVUS Results – Paired Analysis (Group 1) : 

ABSORB Cohort BIVUS Results – Paired Analysis (Group 1) Serruys, PW., PCR 2010.

ABSORB Cohort BOCT Results – Paired Analysis (Group 1) : 

ABSORB Cohort BOCT Results – Paired Analysis (Group 1) Serruys, PW., PCR 2010.

ABSORB Cohort BRepresentative OCT Images (Group 1) : 

ABSORB Cohort BRepresentative OCT Images (Group 1) Serruys, PW., CCT 2010.

ABSORB Extend : 

ABSORB Extend N = up to 1,000 patients at up to 100 sites (Europe, Australia, New Zealand, Latin America, Asia) Device sizes: 2.5 x 18 mm 2.5 x 28 mm 3.0 x 18 mm 3.0 x 28 mm Lesion length treatable:  28 mm Clinical follow up: ID-MACE, ID-TVF, ID-TLR, ID-TVR, ‘stent’ thrombosis 30 days, 6 months, and annually 1-3 years Angiography, IVUS and OCT follow up: Subgroup of patients at selected investigational sites who receive planned overlapping BVS scaffolds to treat long lesions (overlap of two 18 mm long devices also permitted)

Summary : 

Summary Results from ABSORB Cohort A continue to be encouraging, with only one MACE and no thrombosis through 3 years of follow up ABSORB Cohort B has demonstrated a low incidence of adverse events, no thrombosis, and metallic DES-like angiographic late loss at 6 months follow up ABSORB EXTEND is aimed at building a body of scientific data to support this revolutionary technology If fully bioresorbable technology permits restoration of natural vascular integrity and function, it may provide unique physiologic benefits to patients In the future, ‘Vascular Restoration Therapy’ could provide greater durability of results following PCI, a concept that must be tested in future trials