Transcript slides

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 = 15494 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