1. November 9, 2015
February 20, 2017
Using real world evidence – industry perspective Pma indication expansion
Melissa hasenbank, phd
Sr. Clinical Research Manager
Jenny andersen
Regulatory Affairs Director

2. Melissa Hasenbank is an employee of Medtronic, plc.
disclosures
Melissa Hasenbank is an employee of Medtronic, plc.
Jenny Andersen is an employee of Medtronic, plc.
CRT 2017 | February 20, 2017

3. Using Real-World Evidence: An industry example
Medtronic is providing a recent example for an indication expansion using real- world evidence (RWE) for a Class III drug-coated balloon (DCB)
Medtronic relied on recent FDA Guidance to support the proposed indication expansion
Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval (April 13, 2015)
Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices (July 27, 2016)
Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions (December 27, 2016)
The indication expansion utilized data from a Medtronic-sponsored single-arm study in patients treated with DCB and control data from a large national registry
The pre-submission process was utilized for discussions and alignment with FDA
Ability to leverage existing data in the original PMA (preclinical/clinical)
Use of real-world data
Development of a prospective analysis plan
CRT 2017 | February 20, 2017

4. In.pact™ admiral™ drug-coated balloon
Intended Use
To treat peripheral artery disease of the superficial femoral or popliteal arteries
Platform
Admiral™ Xtreme Percutaneous Transluminal Angioplasty (PTA) Balloon
4-7 mm diameters
20, 40, 60, 80, 120 and 150 mm lengths
Drug
Paclitaxel
Proven anti-proliferative drug
3.5 µg/mm2
Excipient
Urea
Facilitates drug transfer
Naturally occurring, non-toxic
CRT 2017 | February 20, 2017

5. Regulatory History and clinical Programs
Medtronic commercialized IN.PACT Admiral DCB in March 2009; the global regulatory status is provided below
European Union (CE Mark)
CE Mark received in March 2009
Global
Commercially available in over 90+ countries
United States (FDA)
PMA approval in December 2014
Medtronic has developed several clinical programs to evaluate the safety and efficacy of IN.PACT Admiral DCB in the treatment of peripheral artery disease
IN.PACT SFA Trial
Randomized pivotal trial comparing DCB vs. PTA outcomes
IN.PACT Global Study
Single-arm study evaluating DCB outcomes in a real-world patient population, including subjects with longer lesions and in-stent restenosis
IN.PACT SFA Japan Trial
Randomized trial comparing DCB vs. PTA outcomes in a Japanese patient population
IN.PACT SFA China Study
Single-arm study evaluating DCB outcomes in a Chinese patient population
CRT 2017 | February 20, 2017

6. In-stent restenosis in Peripheral artery disease
Unmet Clinical need
Presence of a foreign body (stent) stimulates proliferation of smooth muscle cells, resulting in neointimal hyperplasia and re-narrowing of the artery
Management of in-stent restenosis (ISR) often requires repeated and complex interventions, which can impact both quality of life and healthcare costs
ISR represented a significant unmet clinical need, as the current approved indication for IN.PACT Admiral DCB included native vessel treatment only and existing approved treatments had low effectiveness results
Stent with ISR
Magnified image showing ISR
CRT 2017 | February 20, 2017

7. Key Regulatory milestones
PMA Approval of in-stent restenosis indication
Original PMA Approval – December 2014
Interactive Discussions with FDA using Pre-submission Process
PMA-S submitted: Request for Indication Expansion – March 2016
FDA Approval of PMA-S – September 2016
CRT 2017 | February 20, 2017

8. items to consider Use of rWE in indication expansion PMA Supplements
Collaboration with FDA is key to successful real-world evidence strategy
Frequent interactions with FDA through pre-submission process
Ability to leverage existing data (preclinical/clinical) from the original PMA
Demonstration of a well designed and conducted clinical evaluation
Ability to demonstrate probable benefits outweigh risks
Careful consultation of the guidance documents
RWE could contribute to valid scientific evidence to support indication expansion
Limitations of data should be known and discussed with FDA prior to analysis
Analysis methods should be strategically planned to reduce bias concerns
IDE requirements and post-market study requirements may still exist
CRT 2017 | February 20, 2017

9. Recent successful Experience using RWE to support a PMA indication expansion
An unmet need was identified, as approved treatments for in-stent restenosis in peripheral artery disease patients had unsatisfactory effectiveness outcomes
Early clinical evidence suggested that a newly approved device had the potential for promising safety and effectiveness outcomes in this expanded indication
Level 1 clinical evidence did not exist for this device in this patient population
An approach leveraging FDA guidance documents on the use of real-world clinical evidence was proposed with a prospectively defined analysis
PMA approval of this expanded indication helped to address the unmet clinical need of in-stent restenosis in peripheral artery disease in the US
CRT 2017 | February 20, 2017

10. Questions?
THANK YOU!
CRT 2017 | February 20, 2017