1. The Biotronik Magnesium Alloy Bioabsorbable Stent Program: Lessons Learned and Future Directions
Ron Waksman, MD
Professor of Medicine (Cardiology) Georgetown University,
Associate Director of Cardiology
Washington Hospital Center Washington DC

2. Ron Waksman, MD DISCLOSURES Consulting Fees Grants/Contracted Research
Abbott Vascular, Biotronik, Medtronic CardioVascular, Inc, Boston Scientific Corporation
Grants/Contracted Research
Abbott Vascular, Biotronik, Boston Scientific Corporation, The Medicines Company, GlaxoSmithKline, Schering-Plough, sanofi-aventis U.S. LLC

3. Magnesium shows positive effects on the vascular system, even in high doses
An essential element for the human body involved in the synthesis of more than 300 enzymes
Quantity in human body: ~ 20 g
Daily need (adult): ~ 350 mg
Weight of Magnesium stent: ~ 3 mg
High concentration of Magnesium (e.g. 2 g infusion) has shown …
to cause vasodilation [Seelig et al. 1983]
to promote the development of collateral vessels in ischemia [Maier et al. 2004]
to directly inhibit acute stent thrombosis [Rukshin et al & 2002]
to act antiarrhythmic [Arnold et al. 2000]
to have neuroprotective effects [Kohno et al. 2007]
San Pellegrino:
Mg: 53.5 mg/l

4. AMS allows non-invasive imaging of the stented vessel
Headline
IVUS/OCT stent visibility
MRI
16 MSCT
Erbel et al, Herz 32 · 2007 · Nr. 34
Left pictures: Coronary magnesium stent implantation into segment 1 of the right coronary artery and visualization by intravascular ultrasound. The stent was not visible by magnetic resonance imaging, but the invisible stent allowed free imaging of the coronary lumen of the artery despite coronary stenting.
Right picture: 16‑slice computed tomography of a magnesium stent in segment 6 of the left coronary artery. The magnesium stent is not visible allowing a free imaging of the artery lumen
MRI/MSCT
No stent artefact
Optimal vessel lumen imaging
Source: Erbel et al, Herz 32 · 2007 · Nr. 4
* …
Source: …
* …
Source: …

5. First in Man Coronary Study of AMS-1: PROGRESS-I
Clinical Performance and Angiographic Results of the Coronary Stenting with Absorbable Metal Stents

6. Results PROGRESS 1 - IVUS
Post implantation
4 months follow-up
Negative
remodeling/
recoil
Thickening
of extra-stent
tissue
In-stent
neointima
Contribution to lumen loss
42%
13.5%
41%
Waksman et al. JACC Intervention 2009

7. TLR occurrence in PROGRESS 1
100 80 60
4-month ANGIO
Ischemic TLR Occurrence 40 20 30 60 90
120
150
180
210
240
270
300
330
Days Post Intervention

8. NLD 014-002 Post Implantation 4 Months 28 Months
Waksman et al. JACC Intervention 2009

9. AUS 004-001 Post Implantation 4 Months 16 Months
Waksman et al. JACC Intervention 2009

10. IVUS Analysis
Waksman et al. JACC Intervention 2009

11. Vessel Reactivity
Intracoronary ISDN induced vasodilatation in Permanent Metal Stent (PMS) control patients and Absorbable Metal Stent (AMS) patients within stent and in proximal reference segments at 4 months post implant.
Courtesy of Dr Miles Dalby
Royal Brompton & Harefield

12. 15 months after AMS implantation in human
Very thin neointima
Perfect ingrowth of AMS
Completed healing of the stented vessel
IVUS
OCT
Dr. Carlo di Mario, London

13. AMS-1 studies demonstrated safety and gave valuable input for improvements
Safe in human coronary and peripheral arteries (150 patients)
No death, no MI, no stent thrombosis, no distal embolization
Device success rate of 99.4%
Absorbed as intended in several months
Fully CT/MRI compatible
Clinical performance comparable to PTA in BTK lesions
High TLR in coronary indication, compared with DES and modern BMS (despite PROGRESS AMS-1 having met the safety and efficacy primary endpoint)
The AMS technology is feasible (high procedural success and technical success, absorption of the device allows natural vasomotion)
The AMS provided safety (no death, no MI, no stent thrombosis, no distal embolization, no excessive inflammation)
PROGRESS AMS-1 met the safety and efficacy primary endpoints (MACE <30%)
High TLR, so further improvement of the AMS-1 technology is needed to improve efficacy
BIOTRONIK opted to further improve the AMS-1 technology to improve efficacy

14. neointima hyperplasia
The next generations of AMS address the two main levers for improvement
AMS-1 is being improved by ...
AMS-2
... prolonged mechanical
stability
AMS-3
... reduction of
neointima hyperplasia
Improved stent design
Surface passivation
“DREAMS” = Drug elution
Modified Alloy

15. AMS-2 technology: A leap forward
Strut Cross-Sections
AMS-1
AMS-2
165µm
120µm
Changes made
Alloy with slower degradation
Lower strut thickness
Surface modifications
Modern 6-crown design
Effects (in animal)
Prolonged scaffolding and stent integrity
Less neointima proliferation
Increased radial strength

16. AMS-2.1 provides competitive mechanical performance
Tailor-made specialty Magnesium alloy with slow degradation
Available sizes
Diameters of 3.0/3.25/3.5mm
Lengths of 12/16/20mm
Proven SDS based on „ProKinetic“ bare metal stent system
Favorable mechanical properties (values for 3.0mm stent version)
Elastic recoil: 5%
Collapse pressure: 1.2 bar
Crossing profile: 1.3mm
6F compatible

17. BIOTRONIK DREAMS AMS 3 Eluting Stent System
Drug:
Fast degradable carrier with a proven, anti-proliferative drug
First animal trials show sustained anti-proliferative effect up to 1 month
Drug elution kinetic is currently optimized
Stent:
Bioabsorbable Magnesium Alloy
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Carrier:
Bioresorbable Matrix Modifications for control drug release

18. DREAMS: Drug Eluting Absorbable Metal Stent
POLYMER
Δ Drug Elution Rate
Drug Degradation
DRUG
STENT
Drug Degradation

19. DREAMS: Drug Eluting Absorbable Metal Stent
DE Formulation identified that demonstrates controlled release of conventional anti-proliferative drug from AMS
% Cummulative Release
Controlled Drug
Elution
DE Coating on Mg demonstrating
Mechanical Integrity & Stability
(Post-Sterile)
In Vitro Drug Elution
from Mg AMS Stent

20. DREAMS: Drug Eluting Absorbable Metal Stent
Significant Improvement in MLD with DREAMS at 14d and 28d vs. Bare AMS in Porcine Model
TIME

21. DREAMS: Drug Eluting Absorbable Metal Stent
Demonstration of Drug Activity in Porcine Coronary Model at 28 days with DREAMS
Bare AMS
DREAMS
Significant Reduction in Neointima Thickness
Between DREAMS and Bare AMS
TIME

22. Summary
The BIOTRONIK's Mg Absorbable Metal Stent technology is based on a specialty Magnesium alloy that offers superior stent mechanics and biocompatibility
The first generation of Absorbable Metal Stents (AMS-1) showed promising results regarding mechanical properties as well as feasibility and safety in several human applications (150 cases)
The second generation (AMS-2) shows improved scaffolding and efficacy in animal based on a more slowly degrading Magnesium alloy and an optimized stent design
The preclinical studies of AMS-3 have demonstrated positive results allowing the clinical program to resume in 2010 22