A Novel Sustained Limus Release Eluting Balloon: 2-Year Data from the SELUTION SFA Trial Thomas Zeller, MD Universitaets-Herzzentrum Freiburg Bad Krozingen, Germany
DISCLOSURE STATEMENT OF FINANCIAL INTEREST Thomas Zeller, MD For the 12 months preceding this presentation, I disclose the following types of financial relationships: • Honoraria received from: Abbott Vascular, B. Braun, Biotronik, Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Philips-Spectranetics, TriReme, Veryan, Shockwave • Consulted for: Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics, Veryan, Intact Vascular, MedAlliance, Vesper Medical • Common stock: QT Medical Thomas Zeller
Drug Coated Balloon Clinical Need ▶ Novel angioplasty balloon coated with an anti-restenotic drug ▶ Overcoming unmet clinical need : ▶ Homogenous delivery of anti-restenotic drug reduces amount of restenosis ▶ Due to absence of any stent no stent fracture or vessel injury ▶ Allows original anatomy to remain intact Positive remodeling ▶ “Leaving nothing behind” allowing fast ‘normalization’ of vascular function ▶ True normalization of vasomotor function, ▶ Restoration of physiological responses to stress ▶ NO long-term consequences related to inflammation, accelerated atherosclerosis and thrombosis ▶ No need for long term DAPT Thomas Zeller
Ptx On Balloons: Easier, Not Better ATTRIBUTE LIMUS PACLITAXEL Mode of action Cytostatic Cytotoxic Margin of safety 10,000 fold 100 fold Anti-restenosis Optimal Good Tissue absorption More difficult Easier And elution Level of competition Low Very high Positive Controversial Physician perception Thomas Zeller Source: Oral presentation TCT 2016, P. Stella.
Sirolimus Coated Balloon Challenges PACLITAXEL SIROLIMUS Absorbs quickly and tends to Absorbs slowly and spreads ► ► localize in sub-intimal space and throughout entire artery where it partitions significantly in adventitia dilutes down to sub-therapeutic levels Sirolimus Adventitia Paclitaxel Media Intima Dextran Plaque Drug Balloon Tissue Binding Capacity (TBC) of labeled Dextran, Paclitaxel and Sirolimus in 0.040-mm-thick bovine internal carotid tissue segments. Thomas Zeller Source: PNAS 2004:101(25); 9463 – 67
Sirolimus-Eluting Balloon with Sustained Release Proprietary Micro-reservoir Technology ● Micro-reservoirs combining sirolimus & biodegradable polymer ● Sirolimus - a proven safe & effective cytostatic drug ● Offering a wider therapeutic range Micro-reservoirs: Miniature Drug-Delivery Systems ● Optimal size micro-reservoirs achieve elution kinetics similar to best in class DES ● Controlled and sustained release of sirolimus ● Providing therapeutic effect for over 60 days Cell Adherent Technology (CAT™) Proprietary amphiphatic lipid technology binds micro-reservoirs to balloon surface ● Contains and protects micro-reservoirs during insertion and inflation ● Facilitates higher drug transfer efficiency allowing for low drug dose on balloon surface ● Maximises drug bioavailability Thomas Zeller *Device not approved and available for sale in the US
SELUTION SLR ™ SIROLIMUS DEB 6 Arterial Tissue Drug Concentration Drug Dose per Balloon Size Sirolimus (RAP) versus Paclitaxel (PAX) 300 12 Tissue Drug Concentration [ug/g] Med Alliance SELUTION - 1.0 μ g/mm2 262 9.9 Med Alliance SELUTION - RAP 10 250 Bard LUTONIX - 2.0 μg/mm2 Bard LUTONIX - PAX Drug Dose [mg] Medtronic IN.PACT - 3.5 μg/mm2 8 200 Medtronic IN.PACT - PAX 5.7 150 6 Therapeutic Effect ≥ 1 µg/g 100 4 2.8 59 1.8 44 50 2 1.0 35 21 19 0.5 11 3 1 0 0 0.3 0 0 1 hour 7 days 28 days 60 days 4.0x40 6.0x150 En Face Scanning Electron Microscope at 24 hours SEM Courtesy of Renu Virmani Source: Med Alliance – Pharmacokinetics Study (2014-004) – Thomas Zeller Medtronic – Presentation R.J. Melder (LINC 2012) – Bard – Catheterization and Cardiovascular Interventions 83:132 – 140 (2014)
SELUTION SLR ™ vs. Competition Drug Transfer 100% % of Total Device Drug Load 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Med Alliance Bard Medtronic SELUTION LUTONIX IN.PACT Lost during procedure 36% 83% 83% Retained on balloon 25% 12% 14% Transferred to vessel (1 hr) 39% 5% 3% Source: Med Alliance – Bench Test Data on File Thomas Zeller Bard-LUTONIX & Medtronic-IN.PACT – Presentation Granada at CRT 2014.
SELUTION SLR™ COATING DURABILITY ► Coating Durability during handling and deployment NO FLAKING Thomas Zeller
SELUTION SFA FIM TRIAL ClinicalTrials.gov ID: NCT02941224 To assess the safety and efficacy of the SELUTION SLR DEB in treatment of de-novo occluded/stenotic or re-occluded/restenotic lesions of SFA OBJECTIVES and/or PA, assessed at multiple time points clinical, angiographic and/or ultrasound assessment ▶ Prospective, controlled, multi-center, open, single-arm clinical DESIGN investigation ▶ 50 patients PRIMARY ▶ Angiographic Late Lumen Loss (LLL) by QVA – 6M ENDPOINTS ▶ Major adverse Events (Death, Thrombosis, Amputation, CD-TLR) 6M ▶ Primary Patency – Freedom from CD-TLR and absence of Restenosis by DUS - 6, 12 and 24M ▶ Angiographic Binary Restenosis (ABR) by QVA – 6M SECONDARY ▶ Composite of Freedom from Amputation and Freedom from CD- ENDPOINTS TVR – 12 and 24M ▶ Change of ABI, WIQ and Qol - 6, 12 and 24M Thomas Zeller
SELUTION SFA Trial Design KEY INCLUSION CRITERIA KEY EXCLUSION CRITERIA • SFA & Popliteal Artery (PA) • Known hypersensitivity or contra-indication to aspirin, heparin or other anticoagulant / • Male or non-pregnant female anti-platelet therapies ≥ 18 years of age • Prior vascular surgery of target lesion • De-novo or restenotic lesion(s) with composite length ≤ 15 cm • Known inadequate distal outflow / significant inflow disease • Target vessel reference diameter ≥ 3.0 mm and ≤ 7.0 mm • Remaining acute or sub-acute thrombus in target vessel • Multiple target lesions can be treated with • Use of adjunctive treatment therapies (i.e. maximum of 2 overlapping DCBs laser, atherectomy, cryoplasty, • Rutherford class 2-3-4 scoring/cutting balloon, etc.) Thomas Zeller
SELUTION SFA Trial Management TRIAL CENTERS Herzzentrum Bad Krozingen T. Zeller (PI) Franziskus Krankenhaus, Berlin K. Brechtel Vivantes Klinikum Neukoelln, Berlin T. Albrecht Hubertus Krankenhaus, Berlin D. Meyer CRO CORELAB SPONSOR Independent CEC committee P. Gaines, M. Lichtenberg, G. Tepe Thomas Zeller
SELUTION SFA Trial Patient Flow Chart Enrollment: Oct 26th 2016 – May 23rd 2017 Not Eligible N=35 Non-Clinical Withdrew Consent Prior to SCREENING Inclusion / Exclusion Criteria Procedure N=1 Screened N=88 Withdrawn by Site N=2 SELUTION TM DCB PROCEDURE N=50 Bailout Stenting N=4 Withdrew N=2 Completed N=43 (86%) DUS Completed N=43 Missed Visit N=5 6 M FOLLOW-UP Angio FU Completed N=34 (68%) Completed N=47* (94%) Missed Visit N=1 12 M FOLLOW-UP DUS completed N=37 (74%) * 10 Patient telephone contact only: TLR & Vital status Withdrew N=2 Completed N=42* (84%) 24 M FOLLOW-UP Lost to FU N= 4 DUS completed N=38 (76%) Thomas Zeller *4 Patient telephone contact only: TLR & Vital status
SELUTION SFA Trial Baseline Characteristics CLINICAL LESION N=50 N=50 CHARACTERISTICS CHARACTERISTICS Age, Y ± SD 69.6 ± 10.4 De Novo 96% (48) Lesion Length, mm ± SD 64.30 ± 42.8 Male, % (n) 58% (29) RVD, mm ± SD 5.1 ± 0.8 Previous Intervention, % (n) 30% (13) % Diameter Stenosis, % ± SD 90 ± 8.0 Myocardial Infarction, % (n) 6% (3) Occlusion 30% (15) Renal Insufficiency, % (n) 22% (11) Calcification Hypertension, % (n) 80% (40) None 12% (6) Hyperlipidemia, % (n) 90% (45) Mild 44% (22) Diabetes (Type 2), % (n) 28% (14) Moderate 10% (5) Smoking History, % (n) 58% (29) Moderately severe 26% (13) Anticoagulation Therapy 22% (11) Severe 8% (4) Angina Pectoris 14% (7) Target Lesion Location, % (n) SFA prox 12% (6) SFA mid 34% (17) SFA dist 54% (27) POP 1 24% (12) POP 2/POP 3/TPT 16% (8) Thomas Zeller
SELUTION SFA Primary Endpoint LLL at 6M (N=34) LLL 3,5 3 2,5 2 1,5 1 0,5 0.19 mm* 0 0 5 10 15 20 25 30 35 -0,5 -1 -1,5 • Calcified Target Lesion (CoreLab assessed by 360 score) Thomas Zeller *Late Lumen Loss presented as median value
SELUTION SFA Minimal Lumen Diameter Pre FU Post 0.80 ± 0.73 3.24 ± 1.02 3.62 ± 0.71 100 Cumulative density function 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 MLD (mm) Pre Post Follow-up Thomas Zeller
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