Magmaris Stent (Biotronik) A Pichard, Ron Waksman. Medstar Washington Hospital Center Washington, DC

Transcription

1 Magmaris Stent (Biotronik) A Pichard, Ron Waksman. Medstar Washington Hospital Center Washington, DC

2 Conflict of Interest None for this presentation

3 Downside of Metallic Stents 1. Restenosis No longer a problem if optimal PCI accomplished. More frequent in Diabetes and Diffuse disease Still a problem in small vessels

4 Downside of Metallic Stents 2. Thrombosis Often a devastating clinical event Mostly prevented by optimal PCI technique and adequate DAPT. More prevalent in patients with acute coronary syndrome, complex lesions and long stents

5 Downside of Metallic Stents 3. Neo Atherosclerosis Develops in BMS and DES Plaque rupture/thrombosis can lead to STEMI. Appears not be related to hyperlipidemia (inflammatory?). At this time, an unpredictable event (specially now that routine NI testing is no longer approved).

6 Downside of Metallic Stents 4. Stent Fracture Occurs in up to 17% of patients (CT data) Can develop aneurysm, restenosis, acute thrombosis

7 Downside of Metallic Stents 5. Eliminates physiologic vasomotion of the coronary artery. Issue for athletes (hyper thrombogenicity of exercise). Associated with neoatherosclerosis

8 Advantage of Spot Stenting The less metal in the coronary artery, the less chance of: restenosis, thrombosis, stent fracture, neoatherosclerosis, inhibition of physiologic vasomotion. Stent should be used for the short segment of 90% stenosis and leaving the 50% borders unstented. Medical therapy is better for intermediate lesions than stenting them.

9 The Magmaris backbone is flexible and robust 8 Corrugated rings Open cell design for acute flexibility 2 links, 90 shifted Uniform flexibility in all 3D directions 6 crown design. Radial support Strut dimension 150x150µm Radial support

10 Magmaris description Mg Backbone resorbable Double eye radiopaque marker (Tantalum) permanent Coating resorbable Mg Backbone resorbable 9

11 Magnesium alloy scaffold Mg Alloy Mixture of 2 metals or other elements. Grain size reduction & homogenization Alloy Structure can modify: Mechanical properties Resorption behavior Biocompatibility Design Design define the final scaffold performance. 10 Document identifier

12 First Step: Magnesium Hydroxide 0m 1m 3-9m 12m Magnesium Magnesium hydroxide Magnesium phosphate Amorphous Calcium phosphate Mg + 2 H2O Mg(OH)2(s) + H2(g) Magnesium + Water Magnesium hydroxide Physiological environment with high water content 11

13 Second and Third Step: Magnesium Phosphate and Amorphous Calcium Phosphate (ACP) 0m 1m 3-9m 12m Magnesium Magnesium hydroxide Magnesium phosphate Amorphous Calcium phosphate Mg(OH) 2 (s) + HPO 4 2- (aq) + Ca 2+ (aq) + H 2 O (l) Ca x (PO 4 ) y n H 2 O (s) + H 3 O + (aq) + Mg 2+ (aq) Magnesium hydroxide Magnesium + Phosphate ions phosphate Physiological environment with high water content 12 + Calcium ions Amorphous Calcium Phosphate + Magnesium ions

14 Magnesium inhibits platelets and prevents thrombosis Mg concentration Platelet activation Prevention of thrombosis 1 Castiglioni et al. (2015). BioNanoMat; 16(1): 23 29; 2 Kolte et al. (2014) Cardiology in review;22(4):

15 Magnesium Reduces Vascular Calcification Mg suppresses the transformation of vascular smooth muscle cells into calcifying (osteogenic) cells 1-3 Mg intake correlate with reduced calcification of the coronary arteries 4* 1 Castiglioni et al. (2015). BioNanoMat; 16(1): 23 29; 2 Kircelli et al. (2011). Nephrology Dialysis Transplantation; 0: 1 8; 3 de Oca et al. (2014). PloS one ;9(2):e89525.; 4 Hruby et al., (2014): JACC Cardiovasc Imaging; 7(1): Similar conclusions from another study: Posadas-Sánchez et al. (2016) Nutrition Journal; 15:22 *Increase of Mg levels is associated with reduced calcification in the tunica media **The systemically available magnesium from Mg intake per day tested in this study was 15 mg, while the magnesium released locally by the BIOTRONIK Mg Scaffold during one year is around 10 mg. 15 CONFIDENTIAL Internal Use Only

16 - with Magmaris Limus drug - antiproliferative drug The Limus drug is a natural antibiotic and potent immunosuppressive agent. PLLA - resorbable polymer Providing a controlled drug release up to 90 days and is metabolized by the body into carbon dioxide (CO2) and water (H2O) 17

17 Mg vs polymeric backbone Polymeric Scaffold Mg Scaffold Polymeric Scaffold Strut thickness Mg Scaffold 3.0/ / µm 150 µm Strut width 180 µm 150 µm sharp round Cross section Rectangular Sharp edges Square Rounded edges µct comparison Polymeric scaffold Mg Scaffold 18 Document identifier

18 Magmaris allows single step inflation Magmaris Single step inflation of the balloon Absorb Stepwise inflation of the balloon Inflate the dilatation balloon slowly to expand the scaffold to the diameter in accordance with the compliance chart on the label. Maintain inflation pressure for at least seconds for full expansion of the scaffold. 2 Deploy the scaffold slowly, by pressu-rizing delivery system in 2atm increase-ments, every 5 seconds, until scaffold is completely expanded. Maintain pressure for 30 seconds ABSORB IFU Magmaris IFU 2016

19 Magmaris: deliverability 2 0 Lesion crossing Trackability Pushability * vs leading polymeric scaffold Source: IIB, BIOTRONIK data on file

20 Magmaris: mechanical acute robustness * vs the leading polymeric scaffold 2 1 Radial resistance no significant diameter change under increasing physiological load Source: IIB, BIOTRONIK data on file Less recoil conventional polymeric scaffold diameter decrease >20% within 1st hour *

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22 Magmaris resorption on OCT Post-Implantation 6 month 12 month Immediately after implantation, struts are well apposed to the vessel wall. While the Magnesium resorption process continues, endothelialization progresses. At 12 months after implantation, the Magnesium resorption is almost completed. 23 Document identifier

23 Vasomotion at 12-month follow-up (n=16) 2.61 ± 0.51 MLD Proximal (mm ± SD) 2.45 ± 2.68 ± ± 0.34 MLD Scaffold (mm ± SD) 2.42 ± 2.62 ± ± 0.36 MLD Distal (mm ± SD) 2.00 ± ± % (13/16) demonstrate 3% vasomotion after Ach or Nitro Ach = Acetylcholine Nitro = Nitroglycerine 24 Document identifier

24 Magmaris clinical program from FIM to RCT BIOSOLVE I 46 EU + Switzerland FIM TLF at 6 and 12 months Completed BIOSOLVE II 123 Worldwide FIM In-segment LLL at 6 months 12 months FU available BIOSOLVE III 61 EU + Switzerland Pivotal trial In hospital Procedural success Enrolling BIOSOLVE IV 1065 Worldwide PMS Registry TLF at 12 months To start Dec 2016 BIOSOLVE V TBD Worldwide RCT TBD To start 25

25 Results Kinetics Design Evolution of the Biotronik Magnesium Scaffold Device generation AMS 4-month DREAMS 1G 6-month DREAMS 2G 6-month Strut thickness/width 165/80 μm 120/130 μm 120/120 μm (Ø 2.5) 150/150 μm (Ø 3.0 & 3.5 ) Markers none none Ta-composite Coating - drug none PLGA/PTX PLLA/SIR Drug elution kinetics n.a. like Taxus like Orsiro Absorption (mos.) (Mg) 12 (Mg) In-segment LLL (mm) 0.83± ± ±0.37 In-scaffold LLL (mm) 1.08± ± ±0.36 TLF* (%) % Def/Prob Thrombosis *Composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG Document identifier

26 FIM 6-month 12-month N=120 % N=118 % TLF Cardiac Death Target Vessel MI TLR CABG Scaffold def/prob Thrombosis Composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG old smoker, CV RF: hypertension and hyperlipidemia, stable angina CCS Class II, treated with a DREAMS 2G 3.0x20mm in the distal RCA. Patient experienced an unwitnessed death 134 days post procedure. Since a cardiac cause could not be ruled out, patient was adjudicated as cardiac death by the Clinical Event Committee 27 Document identifier

27 Advances in Scaffold Design 1,00 In-Segment Late Lumen Loss [mm] 0, ± % 0,50 0, ± % 0.27± ,00 PROGRESS BIOSOLVE-I BIOSOLVE-II 4-month 6-month 6-month Document identifier

28 Clinical Results until 12-month follow-up 6-month 12-month N=120 % N=118 % TLF Cardiac Death Target Vessel MI Clinically driven TLR CABG Scaffold Thrombosis definite or probable Composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG old smoker, CV RF: hypertension and hyperlipidemia, stable angina CCS Class II, treated with a DREAMS 2G 3.0x20mm in the distal RCA. Patient experienced an unwitnessed death 134 days post procedure. Since a cardiac cause could not be ruled out, patient was adjudicated as cardiac death by the Clinical Event Committee Document identifier

29 In Vivo Serial Assessment of Vessel Geometry Restoration Pre-procedure Post-procedure 6-month 12-month 34 degrees 14 degrees 25 degrees 31 degrees Angulation was defined as the angle in degrees that the tip of an intracoronary guideline would need to reach the distal part of a coronary bend 1 Curvature was defined as the infinitesimal rate of change in the tangent vector at each point of the lumen centerline 1 34 Document identifier 1 Stone P.H. and Feldman C.L., JACC 2010; 3(11):

30 Percentage (%) Serial IVUS Virtual Histology. (11 patients) Fibrous Dense Calcium Necrotic Core Fibrous Fatty 34,88 31,29 29,27 4,57 46,52 43,68 28,64 25,96 20,91 17,25 10,27 6,77 Post-procedure 6 months 12 months

31 OCT Light Intensity analysis 37 Document identifier

32 MAGMARIS Study Portfolio Study Name PI Country Koolen NL Haude DE Haude DE Design # subjects Status / Comment FIM Registry 46/50 subjects 3y FUP FIM Registry 123/121 subjects 1y FUP FIM Registry 54/61 subjects 1 EP Proc. Success 2 EP 1y LLL 3y FUP 3y FUP Completed 1 LLL 6m Published in Lancet, year FUP publ. in June issue of EuroIntv: /EIJY16M06_0 Lancet publication TCT 2015, EuroPCR 2016 European Heart: doi: /eurheartj/ ehw196 Enrollment Postmarket Verheye BE (EU) Registry Lee HG (APAC) 1065 subjects 1 EP TLF 12m 1 EP TLF 12m Endpoint analysis every 200 subjects possible TBD V RCT TBD subjects 1 EP TBD12m Planning phase TBD VI India Registry TBD 100 subjects 1 EP TLF 1m 6m FUP Regulatory trial for Indian market access FUP=Follow-up 41 LLL=Late lumen loss 1 subject in last subject in Enrolment period 1 endpoint Study completed Publication submitte Document identifier clinical study roadmap , SPM Q3 2015,

33 Conclusions Clinical outcome showed low TLF (3.4%) and TLR (1.7%), comparable to other absorbable scaffolds and permanent drug-eluting stents. There was no definite-or-probable scaffold thrombosis until 12-month FUP. Vasomotion is preserved Virtual Histology IVUS showed a decrease in dense calcium content over time, a surrogate endpoint for scaffold degradation. 42 Document identifier