1. The Development of Bioabsorbable Drug-Eluting Stents for Peripheral Vascular Interventions
Ron Waksman, MD, FACC, FSCAI
Professor of Medicine, Georgetown University,
Associate Chief of Cardiology,
Washington Hospital Center, Washington DC

2. Ron Waksman, MD Consulting Fee Abbott Laboratories Biotronik, Inc.
Boston Scientific Corporation
Medtronic, Inc.
Merck and Company, Inc.

3. Honoraria
Abbott Laboratories
Boston Scientific Corporation
Medtronic, Inc. Consulting Fee
Merck and Company, Inc.

4. Why absorbable scaffolds?
Why permanent stents?
Vessel scaffolding is necessary only for a certain, limited time, than the permanent implant has no known advantage
Restoration of natural physiologic vasomotor function
Enable vascular remodeling and tissue adaptation
Elimination of chronic sources of vessel irritation and sources for chronic inflammation
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’

5. Profound neointimal hyperplasia after SFA stenting

6. Amaranth Medical PLLA biodegradable Scaffold
Capabilities:
mm diameters
10-200mm lengths
Stent designs suitable for multiple vascular applications
Coronary
Peripheral
Neuro
First product - superficial femoral artery (SFA) stent 5

7. A First for Bioresorbable Stents -Radial Strength of Leading SFA Nitinol Stents
Amaranth stents show radial strength similar to Nitinol stents

8. Promising Results in Pre-Clinical Studies
Amaranth
Nitinol Control
Amaranth 6x60mm SFA Stent in Porcine Right Ilio-Femoral Region
Amaranth 6x60mm Stent

9. Motivation for Bioabsorbable Stent

10. THE NEW NIGHTMARE
In SFA
Stent fractures
and
In-stent restenoses

11. Bioabsorbable Stents/Bioresorbable Scaffolds
IDEAL

12. Ikagi Tamai Stent CE Mark 2006 For SFA Use

13. Preinterventional Igaki-Stent Result
7/36

15. Patency of the Igaki-Tamai-Stent in the SFA 100 patients SFA study

17. AMS is an absorbable metallic scaffold constructed from a magnesium alloy. AMS is laser cut into a slotted pattern from a tube of a bioabsorbable magnesium alloy, and is deployed via balloon-expansion . It was designed to mimic the mechanical characteristics of stainless steel stents including high collapse pressure (0.8 bar), low acute recoil (<8%), and minimal shortening after inflation (<5%). The stent struts disappear over about 4-months although their position can be continually identified being replaced by calcium apatite complex and phosphorous.
Bosiers M, Deloose K, Peeters P. AMS INSIGHT. CIRSE 2008.

18. In-vivo results animal trials
Quick endotheliasation and gradual absorption
Stent immediately after implant
Ingrowth stent in vessel wall
Gradual absorption Mg-alloy by vessel wall
procedure → /- 10 days → +/- 30 days → +/- 60 days

19. 94.7% Limb Salvage After One Year
Limb Salvage Rate
3M 100.0%
6M 94.7%
9M 94.7%
12M 94.7%
Time
(Days)
Bosiers M, Dendermonde, Belgium; Peeters P, Bonheiden, Belgium

20. High Patency Rate Below The Knee
Primary Clinical Patency
3M 89.5%
6M 84.2%
9M 78.9%
12M 72.4%
Time
(Days)
Bosiers M, Dendermonde, Belgium; Peeters P, Bonheiden, Belgium

21. AMS INSIGHT – 6-M patency results
The AMS device was a tested in the tibial arteries in the AMS INSIGHT trial, the only randomized comparative trial of bioabsorbable scaffolding conducted to date. One hundred seventeen patients with 149 lesions causing critical limb ischemia (CLI) were randomized to receive “stand-alone” percutaneous transluminal angioplasty (PTA) or an AMS. Unfortunately, after 6-months, the patency rate for lesions treated with AMS was significantly lower than the rate of those treated with PTA alone (32% v. 58%; p=0.013). It has been suggested that the unfavorable results were likely attributable to “early recoil in addition to neointima formation” in the AMS group. This device did not contain drug and perhaps since it was designed to dissolve in 4 months the radial strength needed to be maintained for a longer period of time.
Bosiers M, Peeters P, D’Archambeau O, Hendriks J, Pilger E, Duber C, Zeller T, Gussmann A, Lohle PNM, Minar E, Scheinert D, Hausegger K, Schulte K-L, Verbist J, Deloose K, Lammer J. AMS INSIGHT - Absorbable metals stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc. Intervent. Radiol

22. DREAMS, the DRug Eluting Absorbable Metal Scaffold Is Fully Degradable
Drug carrier
Fast degrading polymer
Backbone
Customized Mg-alloy
Good biocompatibility
Drug
Antiproliferative paclitaxel
Sizes used in FIM
3.25/3.5 x 16
6F compatibility
Delivery system
Modified PRO-Kinetic

23. DREAMS Provides Scaffolding and Paclitaxel Release up to 3 Months
Acute
3 months
6 months
9 months
Mg alloy
Paclitaxel release
Scaffolding
Mg degradation product
Polymer Mg Mg
Mg degradation (conversion)
Stable drug carrier layer
Diffusion controlled drug release
Mg degradation completed
Drug release completed
Degradation of polymer
Drug carrier layer degradation completed
Beginning disintegration of Mg degradation product
Source: preclinical studies, data on file.

24. Early Prototypes for “big AMS”
8mm BE AMS
8mm SE AMS

25. ABSORB Scaffold Coating Drug Delivery system 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

26. Absorb™ v. Cypher®
Porcine Coronary Study: Representative Photomicrographs (2x)
Absorb™
1 month
6 months
1 year
2 years
3 years
4 years
Cypher
1 month
6 months
1 year
2 years
3 years
4 years

27. A’ B’ C’ D’ E’ A’ B’ C’ D’ E’

28. First case of a drug eluting resorbable scaffold implantation in the peripheral vasculature: ABSORB BTK
Absorb
Everolimus eluting
Resorbable Scaffold
Peroneal
Artery
Stenosis

29. Peripheral Bioresorbable Vascular Scaffold (BVS) Acute implantation in a porcine iliac artery
Oversized
Nitinol SES

30. Peripheral Bioresorbable Vascular Scaffold (BVS) 6 mos
Peripheral Bioresorbable Vascular Scaffold (BVS) 6 mos. after implantation in a porcine iliac artery
Oversized
Nitinol SES
BVS

31. ESPRIT I: First Clinical Trial to Study Drug Eluting Bioresorbable Therapy for Treatment of Peripheral Artery Disease
Esprit is a drug eluting bioresorbable vascular scaffold that uses PLLA the same polymer and drug as the Absorb BVS
The ESPRIT I trial is a single-arm, multi-center trial designed to evaluate the safety and performance of the Esprit therapy in approximately 30 patients with claudication resulting from PAD of the SFA or iliac arteries.
Up to 10 clinical trial sites in Europe will participate in the trial. Patients will undergo clinical hemodynamic functional and quality-of-life follow-up at one, six and 12 months and at two and three years following the procedure.
December 2011

32. Bioabsorbable Scaffold for PAD
Treating blockages in the SFA is a clinical challenge, as there are unique biomechanical forces exerted on the SFA during normal leg movement, which can lead to restenosis or re-narrowing of the vessel
The drug eluting bioabsorbable scaffold technology is now expanding for the treatment of SFA and BTK lesions.
A bioresorbable drug eluting device, designed to act as a temporary scaffold to support the vessel and then fully dissolve, may change the way we treat peripheral artery disease.