Bioabsorbable Scaffolding: Technology and Clinical Update. PD Dr. Nicolas Diehm, MD, FESC Inselspital, University Hospital Bern, Switzerland

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1 Bioabsorbable Scaffolding: Technology and Clinical Update PD Dr. Nicolas Diehm, MD, FESC Inselspital, University Hospital Bern, Switzerland

2 Disclosures I am not Ron Waksman 1

3 Clinical experience with AMS covers peripheral and coronary indications - resumed with a DREAMS first in man study Bare AMS Drug eluting scaffold (DREAMS) Peripheral Coronary BEST-BTK (N=20) PROGRESS (N=63) INSIGHT (N=117) BIOSOLVE-I (N=46) 2 BEST-BTK: Bosiers et al. Vascular Disease Management 2005;2(4):86-91 PROGRESS: Erbel et al. Lancet 2007; 369: INSIGHT: Bosiers et al. Cardiovascular and Interventional Radiology 2008

4 Bioabsorbable Scaffolding: Coronary Studies First in Man Coronary Study of AMS-1: PROGRESS-1 Clinical Performance and Angiographic Results of the Coronary Stenting with Absorbable Metal Stents BIOSOLVE-1 BIOTRONIKS-Safety and Clinical Performance Of the First Drug-Eluting Generation Absorbable Metal Scaffold In Patients with de Novo Lesions in NatiVE Coronary Arteries 3

5 PROGRESS-1 was set-up as a multicenter, coronary FIM study Design Prospective, multi-center, consecutive, non-randomized FIM (First In Man coronary) study Purpose To evaluate the clinical feasibility of the Absorbable Metal Stent in the treatment of a single de novo lesion in a native coronary artery Primary Endpoints Major Adverse Cardiac Events (MACE) at 4 months (cardiac death, nonfatal MI and ischemia driven TLR) Enrollment 63 patients at 8 international clinical sites 4 Source: Erbel et al. Lancet 2007; 369:

6 PROGRESS-1 enrolled patients with short, single de-novo lesions Angiographic and Procedural Characteristics Lesion class (AHA/ACC) Type A 31 (49.2%) Type B1 27 (42.8%) Type B2 5 (7.9%) Type C 0 (0%) Reference vessel diameter Lesion length 2.76 mm Discrete (<10 mm) 23 (36.5%) Tubular (10 20 mm) 40 (63.5%) Moderate to severe calcification 8 (13%) Stents per patient, mean (SD) 1.13 (0.34) Stent length [mm], mean (SD) (1.75) Procedural success 63 (100%) 5 Source: Erbel et al. Lancet 2007; 369:

7 PROGRESS-1 patients showed typical risk factors Baseline Clinical Characteristics Male 44 (70%) Any diabetes 11 (18%) IDDM 3 (5%) History of Smoking 30 (48%) Hypertension 41 (65%) Hyperlipidemia 39 (62%) Stable angina 52 (83%) Unstable angina 6 (10%) Previous CABG 3 (5%) Previous MI 26 (41%) Previous PCI 15 (24%) History of CVA or TIA 1 (2%) History of PAD 4 (6%) 6 Source: Erbel et al. Lancet 2007; 369:

8 PROGRESS-1 confirmed safety in coronary arteries - but moderate TLR In Hospital 4 Months 12 Months N = 63 N = 63 N = 60 n % n % n % MACE (Cardiac death, nonfatal MI, ischemia driven TLR) Death Q-wave MI (new pathol. Q-waves w/ CK or CK-MB elevated) Non Q wave MI (CK 2x above normal with CK-MB elevated) Ischemic Driven TLR Source: Erbel et al. Lancet 2007; 369:

9 DREAMS Drug Eluting Absorbable Metal Scaffold 80x165!m AMS-1 prolong scaffolding time and inhibit cell proliferation Strut geometry Alloy refinement Drug polymer matrix added DREAMS 130x120!m + 1µm matrix!" Proven clinical safety and feasibility!" In 3 clinical studies!" But efficacy had to be improved!" Proprietary Mg-alloy!" Biodegradable polymer!" Paclitaxel!" 6F compatible 8

10 DREAMS provides scaffolding and paclitaxel release up to 3 months Mg alloy Mg degradation product Polymer acute 3 months 6 months 9 months Scaffolding Paclitaxel release Mg + 2H 2 O! Mg(OH) 2 + H 2 Ca(H 2 PO4) 2 Mg Mg!" Initial Mg degradation!" Stable drug carrier layer!" Controlled drug release!" Mg degradation completed!" Drug release completed!" Degradation of polymer ongoing!" Conversion of degradation product completed!" Drug carrier layer degradation completed!" Beginning of structural disintegration 9

11 BIOSOLVE-I enrolled 46 patients in 6 centers Study Design DESIGN: Prospective, multi-centre, first in man trial 46 patients in 6 clinical sites in Germany, Switzerland, the Netherlands and Belgium PRINCIPAL INVESTIGATOR: J. Koolen, Eindhoven, The Netherlands Cohort 1 Cohort 2 PRIMARY ENDPOINT: TLF* cohort 1 at 6 months cohort 2 at 12 months PARTICIPATION CENTERS: Belgium: S. Verheye, Antwerpen Germany: R. Erbel, Essen, M. Haude, Neuss, C. Hehrlein, Freiburg Switzerland: P. Erne, Luzern Clinical follow-up at 1 month Clinical, QCA, IVUS and OCT** follow-up at 6 month Clinical, QCA, IVUS & OCT** follow-up at 12 months Clinical follow-up at 24 & 36 months 10 *Composite of cardiac death, target vessel myocardial infarction and clinically driven TLR ** optional vasomotion testing *** clinical FUP for cohort 1 also at 12 months and for cohort 2 at 6 months

12 Bioabsorbable Scaffolding: Peripheral Studies BEST-BTK First Clinical Application of the Biotronik absorbable metal StenT Below The Knee INSIGHT-1 Bioabsorbable Metal Stent Investigation in Chronic Limb Ischemia Treatment 11

13 BEST-BTK was set-up as a series of single-center, FIM cases Design Set of 20 FIM (First In Man peripheral) cases, single-center, consecutive, non-randomized Purpose To evaluate the safety and feasibility of the Absorbable Metal Stent in the treatment of infrapopliteal arteries in patients with critical limb ischemia (CLI) Endpoints Primary patency, limb salvage rate Enrollment 20 patients in Belgium were included 12

14 BEST-BTK enrolled patients with critical limb ischemia and short stenoses Demographics Number of patients 20 CLI status Rutherford Class 4 9 (45%) Rutherford Class 5 11 (55%) Lesion Characteristics Lesion length 11 mm [2 20 mm] Average vessel diameter 2.7 mm [2.5 3 mm] Mean diameter stenosis 84% [75 95%] Calcified lesions 14 (70%) Thrombus 3 (15%) 13 Source: Bosiers, et al. Vascular Disease Management 2005;2(4):86-91

15 BEST-BTK results demonstrated promising clinical outcomes Primary patency 3M 89.5% 6M 84.2% 9M 78.9% 12M 73.3% Limb Salvage 3M 100% 6M 94.7% 9M 94.7% 12M 94.7% Primary patency Limb Salvage Number at Risk Time (Days) Number at Risk Time (Days) 14 Source: Bosiers, et al. Vascular Disease Management 2005;2(4):86-91

16 BEST-BTK established first evidence of safety and efficacy for AMS!" AMS implantation is safe!" AMS provides good vessel scaffolding!" AMS is absorbed as intended (CFDU, MR)!" AMS remains patent This first clinical experience indicated that AMS is a safe and effective therapy for infrapopliteal stenting 15

17 INSIGHT-1 was set-up as a randomized study against PTA below-the-knee Design Prospective, multi-center, randomized clinical trial Purpose Assess the efficacy and safety of AMS-1 for the treatment of infrapopliteal lesions in patients with CLI Primary Endpoints!" Patency of the AMS determined with intra-arterial Digital Subtraction Angiography (DSA) at 6 month follow-up!" Complications 1 month post-procedure (major amputations defined as amputations at or above the ankle or any cause of death) Enrolment 117 patients in 15 sites, finalized

18 INSIGHT-1 enrolled CLI patients with short lesions below the knee Demographics PTA Only AMS p value Number of patients Male 71.9% 51.7% 0.04 CLI status Rutherford Class % 26.7% Rutherford Class % 73.3% 0.87 Lesion Characteristics Lesion length (mm) 12.5± ± RVD (mm) 2.7± ± MLD (mm) 0.8± ± Percent Diameter Stenosis (%) 68.7± ± Calcification (%) 45.3% 48.6%

19 A typical INSIGHT-1 case shows good immediate results and slight lumen loss at 6 months Angiographic evolution in AMS case Pre Post 6M 18 Source: Bosiers, CIRSE 2008

20 INSIGHT-1 clinical outcomes showed no difference between PTA and AMS Primary patency 2M 91.2% 4M 89.6% 6M 80.2% Limb Salvage 2M 93.2% 4M 91.4% 6M 87.6% ITT: Patency PTA 58% vs AMS 31.8% (p=0.013). 19 Source: Bosiers, Cardiovascular and Interventional Radiology 2008, OnlineFirst

21 INSIGHT-1 failed to show superiority over PTA!" AMS was successfully used in cases with suboptimal PTA results (bail-out cases)!" The study confirmed the safety of the AMS technology (procedural and device success)!" The clinical outcome between the PTA and AMS groups is comparable (limb salvage, Rutherford status)!" AMS shows lower patency compared to PTA 20

22 Summary!" Absorbable metal scaffold is safe and feasible!" A prolongation in scaffolding time as well as an antiproliferative drug were added to DREAMS!" BIOSOLVE-I, the FIM study for DREAMS, included 46 patients in 6 centers!" Results of the first cohort of BIOSOLVE-I will be presented at EuroPCR