1. Opportunities to Study Valve Iterations and Modifications in the US
Rhonda J. Robb
Medtronic

2. Rhonda Robb, MBA
Employee: Medtronic

3. The Challenge: TAVR is Novel ….

4. The Opportunity
Developing, and innovating a platform that is well characterized technically and advances clinical outcomes

5. Transcatheter Valve Requirements
US FDA Requirement
ISO Requirement

6. Computational Modeling
CoreValve Testing
Computational Modeling
Bench Testing
Material Properties
Hydrodynamic assessment
Structural Performance
Delivery System Requirements
Simulated Use
Usability/Human Factors
Pre-Clinical In-Vivo Assessments
Clinical Assessments
Bench Testing
Animal Studies

7. > 5,000 Patients in CoreValve® US Pivotal
Medtronic CoreValve US Pivotal Trial
Up to 687
790
Extreme Risk Screened
High Risk Screened
N=737
N=995 No
Yes
Up to 200
487
395a
395
CoreValve
Transfemoral
CoreValve Non-Ilieofemoral
CoreValve
SAVR
Pivotal
N=470
N=150
N=390
N=357
Alternative Access
Continued Access
CoreValve
ER CAS
CoreValve
HR CAS
N=1623
N=1034
Primary Endpoint: All-cause mortality or major 12 months (compare to perf goal)
Primary Endpoint: All-cause 12 months

8. CoreValve Clinical Results
Extreme Risk Study support the safety and efficacy of this therapy who are deemed unsuitable for surgical aortic valve replacement
Survival at 1 year was superior in patients that underwent transcatheter replacement with CoreValve at high risk for surgery
2 year results at ACC LBCT

9. Significant Global TAVR Evidence Base
More than 70,000 Patients Enrolled Globally in Pivotal Trials, National and Industry Registries
Int’l

10. Delivery Systems Portfolio
Next Generation Valve Systems Building on Proven Foundation w/>75,000 implants
Self-Expanding
Nitinol
Porcine
Pericardium
Delivery Systems Portfolio

11. Evolut R Building on Proven Foundation
Reduced Outflow Height
Fit in angulated anatomy
Supra-annular Valve
Porcine Pericardial Tissue
Conformable Seal
Optimized oversizing /radial force, extended skirt
Recapturable Delivery System
Ergonomic handle, 1:1 response, self-centering, with 14Fr Inline Sheath

12. Evolut R IDE Now Enrolling in the US
PURPOSE
Assess safety and efficacy of CoreValve Evolut R system in patients with severe symptomatic aortic stenosis who are considered high through extreme risk for SAVR
DESIGN
Single arm, non-randomized, multi-center up to 25 sites with follow-up through five year
DEVICES
Evolut R TAV (sizes 23, 26 & 29mm), EnVeo R delivery catheter system with InLine sheath
SCOPE
Minimum of 150 implanted subjects, up to 250 implanted subjects
ENDPOINTS
Safety: 30-day all-cause mortality, disabling stroke
Efficacy: Device success rate (VARC II), percentage subjects ≤ mild early echo
Feb 2015: FDA approval received for the addition of Evolut R Into the SURTAVI Trial

13. Dramatic Difference on Time to Approval
CoreValve Extreme
Risk FDA Approval
Jan 2014
CoreValve CE
Apr 2007
CoreValve High
Risk FDA Approval
July 2014
2007
2014
2015
2016
~ 7 Years
CoreValve
Evolut R CE
Jan 2015
Est FDA Approval
< 1 Year
2015
2016
Evolut R

14. Future Considerations
Early feasibility path offers a very innovative mechanism for study of new concepts (e.g. pulmonic, mitral)
Need to assess future pathways for studying future patient populations given increased challenges to randomize (e.g., lower risk, bicuspid, pure AI)

15. Summary
CoreValve self-expanding platform has established a solid foundation of safety and effectiveness data
System design modifications can be evaluated:
Using refined bench test and pre-clinical models to be more predictive of human outcomes
Through clinical studies with lower patient numbers, shorter term data (e.g. Evolut R) and novel clinical trial constructs
By incorporating into ongoing longer term studies (e.g. addition of Evolut R to Surtavi)

16. Thank You