Development of a TMVR Device Challenge to Innovators

Transcription

1 Development of a TMVR Device Challenge to Innovators Eberhard Grube MD, FACC, FSCAI, FAPSIC University Bonn, Heart Center, Bonn, Germany Stanford Universuty, School of Medicine, Palo Alto, CA

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Grant/Research Support Consulting Fees / Honoraria Minor Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit (Advisory Board, Proctor) Company Nil Boston Scientific, Medtronic, Valtec Biosensors, Symetis M-Valve, Mitralign, Valtec, Twelve, Claret, Shockwave Nil Nil Nil Medtronic, Boston Scientific,

3 Outline Why are we here? Innovator s Challenges in Cardiology Challenges in Mitral Valve Disease Differentiate DMR and FMR Repair vs. Replacement Brief Parade of Technologies Additional and Final Thoughts

4 Why Are We Here?

5 Premature?

6 Edwards Lifesciences Corporation Completes Acquisition Of CardiAQ PR Newswire IRVINE, Calif., Aug. 26, 2015 Edwards Lifesciences (EW) Acquires CardiAQ Valve Technologies in $400 IRVINE, Calif., Aug. 26, 2015 /PRNewswire/ -- Edwards Lifesciences Corporation Million (NYSE: EW), Deal the global leader in the science of heart valves and hemodynamic monitoring, today announced that it has closed its acquisition of CardiAQ Valve Technologies, Inc., a privately held company and developer of a transcatheter mitral valve replacement system. Edwards announced last month that it had signed an agreement to acquire CardiAQ. Medtronic (MDT) to Acquire TMVR Device Developer Twelve in $458M Deal Abbott said it has agreed to acquire the equity in Minnesota-based Tendyne Holdings Inc that it does not already own for $225 million plus future payments tied to regulatory milestones. Abbott already had a 10 percent stake in the company worth about $25 million. Abbott (ABT) to Acquire Tendyne Device in $225M plus Milestones Deal

7 There is a Market Opportunity!

8 Mitral Regurgitation Unmet Clinical Need!

9 Prevalence of Valve Disease Prevalence of Mitral Valve Disease 2-3x larger than Aortic

10 Survival with Mitral Valve Disease Patients with mitral valve disease are often undiagnosed and live 8-10 years with the condition on average. Source: Nkomo, Lancet 2006

11 Opportunity for Transcatheter Mitral Therapies Euro Heart Survey on valvular heart disease revealed that 49% of patients with severe mitral regurgitation are denied surgery Impaired LVEF Older age Comorbidities Source: Eur Heart J. 2007;28:

12 Unmet Clinical Needs for Treating MR Durability of procedure prevention of MR recurrence Awareness and earlier diagnosis to prevent LV dysfunction Patient/general cardiologist acceptance of intervention (vs. watchful waiting) Less invasive, reproducible and safe procedure (no SAM, LVOT etc) Ability to treat wide range of anatomies/etiologies including Rheumatic disease Ease of procedure Repair vs. Replacement? Transcatheter. vs. Surgical?

13 The Challenges!

14 There s something about the Mitral Valve It s not round, nor D shaped but asymmetric It s not flat but saddle-shaped Its annulus is not rigid but dynamic It s not passive but contracts reducing valve area during systole It s a high pressure closure not high pressure opening valve It s got 24+ chords It s easy to block aortic outflow It s easier to get thrombus on Its annulus will eventually change size as the heart fails It s a much larger annulus It s not one disease

15 The Technical Challenge High variability and instability of the anatomy No defined structure for anchoring (like calcified annulus in TAVI) Dilatation of the annulus creates big range of sizes Complex apparatus with multi intra-dependencies: LVOT, SAM, Tethering, Continuous dilatation, complex flow and motion patterns through the cardiac cycle. Delivery challenges: Trans-apical - thin and dilated ventricles Retrograde size, navigation, LV interaction Trans septal size, navigation Two pathologies: DMR and FMR

16 Types of Mitral Regurgitation Different Etiology and Treatments Mitral Regurgitation (MR) Definition Pathology Primary Historical Treatment Degenerative (DMR) Valve abnormalities (leaflet, chord) Weakening Connective Tissue Rheumatic disease Congenital Surgery (Repair/Replacement ) Functional (FMR) Incomplete coaptation caused by heart dilation Ischemic heart disease AMI Non-ischemic cardiomyopathy Medical Therapy

17 But these are only the Technical Challenges the Real Challenges: The treatment solution DMR - Established surgical gold standard which is difficult to imitate FMR - Surgical gold standard is not established Repair? Replacement? Concomitant ventricular procedures?

18 Technology Challenges in Interventional Cardiology Innovation Disease Innovator s Challenge(s) Balloons BMS CAD Recoil Restenosis Thrombosis Solutions Stent DES Imaging Fluoro, IVUS, OCT, FFR-CT DES Scaffolds TAVR Aortic Stenosis Profile/Delivery Paravalvular Leak Positioning Size Reduction Material/Device changes Multiple Access Fluoro, TEE Mitral Mitral Regurgitation Remote location Anchoring Amorphous shape Degenerative and Functional Toolbox will be required, both repair and replacement Fluoro, 2D/3D TEE, CT or MRI

19 Replacement or Repair? Replacement Repair Pros Simpler Versatility Reproducibility Predictable MR reduction Cons Interferes natural hemodynamics Durability? PV leak Safety? Preserves natural hemodynamics Durability Residual MR Allows future intrventions More complex Works in selected patients Learning curve MR reduction less predictable Requires multiple tools?

20 The Dilemma in the eyes of the innovator Replacement? Difficult to achieve but The user will like it more but/and Clinical results are unknown but The device is more prone to safety Repair? Difficult to imitate existing solutions but Safer Device but More complex procedure but Keeping options open May be the solution is not about procedural simplicity but about the etiology of the MV disease and the patients individual disposition (risk etc)?

21 Is there a successful treatment to imitate? Acker: Repair has more recurrent MR but better remodeling De Bonis: Mitral repair should be preferred Common wisdom leans towards repair in earlier stages but no proven mortality benefit and no conclusive data! Acker et al, NEJM 2012 De Bonis et al, Ann Thorac Surg 2012

22 Brief Device Parade

23 Clinical Experience with TMV Repair MitraClip Valtech Mitralign # of Patients > ( implants to date) Type of MR 60% FMR 100% FMR 98% FMR EF < 40% 66% 72% 68% 30-day Survival % MR < 2+ 98% 30-day MACCE 9% * Non-hemorrhagic 1 yr 93.2% 7% * Non-hemorrhagic 30-day 93.2% 15.9% 30-day * EVEREST II High Risk Registry

24 TCMV therapies: Overview Approach Commercial In Clinical In Development Abandoned Valve Replacement Highlife SAS MitraCath Edge to Edge Direct Annuloplasty Indirect Annuloplasty MVRx PS3 Chordal Repair Ventricular Modification Enhanced Coaptation

25 TCMV Replacement in Humans Edwards FORTIS CardiAQ (Edwards) Neovasc Tiara Tendyne (Abbott) Twelve (Medtronic) M-Valve FIM

26 Some Final Thoughts!

27 The Complementary Role Of Transcatheter Techniques Replacement Anuloplasty Mitraclip Stand-alone Annuloplasty: Early treatment FMR Stand-alone Mitraclip: FMR with asymmetric tethering (IMR) Stand-alone Mitraclip: DMR Combined Annuloplasty and MitraClip: DMR and Advanced FMR MV Replacement: advanced DMR and advanced FMR

28 Factors influencing Design of Transcatheter Mitral Therapies Mitral Valve Pathology Absence of Calcium Variable Calcification (MAC) Sub-valvular apparatus Large Effective Orifice Area Large Annular Range Anatomy & Pathology Dynamic Environment Ventricular & Annular Motion High Transvalvular Gradients High Dislodgement Forces Poor Ventricular Function Thin Ventricular Walls Steering Delivery System Profile Access & Positioning

29 Thank you very much for Your Attention!

30 Good Luck