1 UNITED STATES OF AMERICA DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION + + + CENTER FOR DEVICES AND RADIOLOGICAL HEALTH MEDICAL DEVICES ADVISORY COMMITTEE + + + CIRCULATORY SYSTEM DEVICES PANEL + + + April 6, 2021 9:00 a.m. Via Microsoft Teams Videoconference PANEL MEMBERS: RICHARD A. LANGE, M.D., M.B.A. Panel Chair GEORGE W. VETROVEC, M.D., MACC, MSCAI Voting Member JAMES C. BLANKENSHIP, M.D. Voting Member JASON T. CONNOR, Ph.D. Voting Member RALPH G. BRINDIS, M.D., M.P.H., MACC, FSCAI Voting Member KEITH B. ALLEN, M.D. Voting Member MURRAY KWON, M.D. Temporary Voting Member PRAMOD BONDE, M.D. Temporary Voting Member COLLEEN M. GALLAGHER, Ph.D. Temporary Voting Member ALFRED H. STAMMERS, MSA, CPBMT, CCP Temporary Voting Member DAVID YUH, M.D. Temporary Voting Member ROBERT W. YEH, M.D., M.Sc., M.B.A. Temporary Voting Member CRAIG SELZMAN, M.D. Temporary Voting Member MARC R. KATZ, M.D. Temporary Voting Member JOAQUIN E. CIGARROA, M.D. Temporary Voting Member JOHN HIRSHFELD, M.D. Temporary Voting Member ALLEN BURKE, M.D. Temporary Voting Member MARK NUSZKOWSKI, M.D. Temporary Voting Member Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 2 CHRISTOPHER O’ CONNOR, M.D., MACC Temporary Voting Member JEFFREY BORER, M.D. Temporary Voting Member MARC MOON, M.D. Temporary Voting Member DEBRA DUNN Patient Representative GARY JARVIS Industry Representative ADEN ASEFA, M.P.H. Designated Federal Officer Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 3 FDA REPRESENTATIVES: BRAM ZUCKERMAN, M.D. Director, Office of Health Technology 2 (OHT 2: Cardiovascular Devices) Office of Product Evaluation and Quality SHIRLEY SIMSON Press Contact FDA PRESENTERS: CATHERINE P. WENTZ, M.S. Chemical/Biomedical Engineer Lead Reviewer, Circulatory Support Devices Team Division of Health Technology 2 B (Circulatory Support, Structural and Vascular Devices) Office of Health Technology 2 (OHT 2: Cardiovascular Devices) Office of Product Evaluation and Quality XUAN YE, Ph.D. Mathematical Statistician Division of Clinical Evidence and Analysis 2 (Biostatistics) Office of Clinical Evidence and Analysis JOHN S. SAPIRSTEIN, M.D. Office of Health Technology 2 (OHT 2: Cardiovascular Devices) Office of Product Evaluation and Quality ANDREW FARB, M.D. Office of Health Technology 2 (OHT 2: Cardiovascular Devices) Office of Product Evaluation and Quality FERNANDO AGUEL, MSE Assistant Division Director, Circulatory Support Devices Team Division of Health Technology 2 B (Circulatory Support, Structural and Vascular Devices) Office of Health Technology 2 (OHT 2: Cardiovascular Devices) Office of Product Evaluation and Quality Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 4 SPONSOR PRESENTERS: WALEED HASSANEIN, M.D. President/CEO TransMedics MARYJANE FARR, M.D. Associate Professor of Medicine, Division of Cardiology Medical Director, Adult Heart Transplant Program Columbia University Irving Medical Center/New York Presbyterian Hospital JACOB SCHRODER, M.D. Assistant Professor of Surgery Surgical Director, Heart Transplantation Program Duke University School of Medicine CHRIS MULLIN, M.S. Director, Product Development Strategy NAMSA ASHISH SHAH, M.D. Professor of Cardiac Surgery Alfred Blalock Endowed Director and Chairman Department of Cardiac Surgery Vanderbilt University Medical Center SPONSOR ADVISORS: ANTHONY J. DEMETRIS, M.D. Starzl Professor of Liver and Transplant Pathology University of Pittsburgh MIRIAM PROVOST, Ph.D. Vice President, Global Regulatory Affairs TransMedics CARMELO A. MILANO, M.D. Chief, Adult Heart Surgery/Professor of Surgery Duke University Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 5 OPEN PUBLIC HEARING SPEAKERS: NINA ZELDES, Ph.D. Project Manager/Senior Fellow National Center for Health Research DAVID KLASSEN, M.D. Chief Medical Officer United Network of Organ Sharing SEAN PINNEY, M.D. Co-Director, Heart and Vascular Institute Director, Advanced Heart Failure, Transplant and Mechanical Circulatory Support University of Chicago Medical Center GREGORY COUPER, M.D. Surgical Director, Advanced Heart Failure Program Associate Professor Tufts University School of Medicine JASON SMITH, M.D. Associate Professor of Cardiothoracic Surgery University of Wisconsin Medical Center EXPAND Trial Investigator MANI DANESHMAND, M.D. Director, Emory Heart & Lung Transplantation and Mechanical Circulatory Support Emory University School of Medicine EXPAND Trial Investigator PATRICK SULLIVAN Heart Transplant Recipient Co-Founder, Heart Brothers Foundation RON MALLORY Heart Transplant Recipient with OCS Heart in EXPAND Trial MARK CHIBULSKI Heart Transplant Recipient with OCS Heart in DCD Trial JORDAN KESHLER Heart Transplant Recipient with OCS Heart in DCD Trial GLENN ROCKWOOD Heart Transplant Recipient with OCS Heart in DCD Trial Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 6 INDEX PAGE CALL TO ORDER - Richard A. Lange, M.D., M.B.A. 9 PANEL INTRODUCTIONS 9 CONFLICT OF INTEREST STATEMENT - Aden Asefa, M.P.H. 14 GENERAL ANNOUNCEMENTS - Aden Asefa, M.P.H. 16 SPONSOR PRESENTATION Introduction - Waleed Hassanein, M.D. 17 Clinical Need to Expand Donor Heart Utilization - Maryjane Farr, M.D. 22 Heart EXPAND and EXPAND CAP Trials - Jacob Schroder, M.D. 26 PROCEED II Trial Summary - Waleed Hassanein, M.D. 36 Statistical Considerations for Long-Term Survival - Chris Mullin, M.S. 39 TransMedics Positions on FDA Questions and Training and Post-Approval Programs - Waleed Hassanein, M.D. 41 Clinical Perspective and Benefit-Risk Assessment - Ashish Shah, M.D. 50 SPONSOR Q&A 53 FDA PRESENTATION Device Description; Clinical/Regulatory History; Summary of Nonclinical information; Proposed PAS; Panel Discussion Questions - Catherine P. Wentz, M.S. 74 Clinical Data Sources and Predicted Survival - Xuan Ye, Ph.D. 81 Clinical Review - John S. Sapirstein, M.D. 85 Clinicopathologic Analysis - Andrew Farb, M.D. 106 Post-Approval Study - Catherine P. Wentz, M.S. 111 Clinical Summary - Fernando Aguel, MSE 112 FDA Q&A 113 Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 7 INDEX PAGE OPEN PUBLIC HEARING Nina Zeldes, Ph.D. 124 David Klassen, M.D. 126 Sean Pinney, M.D. 127 Gregory Couper, M.D. 129 Jason Smith, M.D. 131 Mani Daneshmand, M.D. 132 Patrick Sullivan 134 Ron Mallory 135 Mark Chibulski 136 Jordan Keshler 137 Glenn Rockwood 139 SPONSOR RESPONSE TO PANEL QUESTIONS 141 FDA QUESTIONS/PANEL DELIBERATIONS Question 1 181 Question 2 189 Question 3 194 Question 4a 197 Question 4b 203 Question 4c 207 Question 5 211 Question 6a 214 Question 6b 219 Question 7 222 Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 8 INDEX PAGE FDA QUESTIONS/PANEL DELIBERATIONS (cont.) Question 8 225 SUMMATIONS FDA - Fernando Aguel, MSE 231 Sponsor - Carmelo A. Milano, M.D. 232 FINAL COMMENTS Debra Dunn, Patient Representative 235 PANEL VOTE 235 CLOSING REMARKS - Bram Zuckerman, M.D. 253 ADJOURNMENT 253 Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 9 1 M E E T I N G 2 (9:03 a.m.) 3 DR. LANGE: Good morning. I would like to call this meeting of the Circulatory 4 Devices Panel to order. 5 I am Richard Lange, the chairperson of this Panel. I'm president of Texas Tech 6 University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster 7 School of Medicine. I'm a general cardiologist now, but spent most of my formative years 8 as an interventional cardiologist. 9 I note for the record that the voting members present constitute a quorum as 10 required by 21 C.F.R. Part 14. I would also like to add that the Panel members participating 11 in today's meeting have received training in FDA device law and regulations. 12 For today's agenda, the Panel will discuss, make recommendations, and vote on 13 information regarding the premarket approval application, that is the PMA, for the 14 TransMedics Organ Care System (OCS) Heart by TransMedics, Inc. 15 Before we begin, I would like to ask our distinguished Committee members and FDA 16 attending virtually to introduce themselves. Committee members, please turn on your 17 video monitors if you've not done so already and unmute your phone before you speak. I 18 will call your name. At that time please state your area of expertise, your position, and your 19 affiliation. I'll start with Dr. Vetrovec. 20 DR. VETROVEC: Hi, I'm Dr. George Vetrovec, Professor Emeritus, Virginia 21 Commonwealth University, an interventional cardiologist by career. 22 DR. LANGE: Great. Thank you, George. 23 Dr. Blankenship. 24 DR. BLANKENSHIP: Good morning, I'm an interventional cardiologist and currently 25 Professor of Medicine and interim director of cardiology at the University of New Mexico. Free State Reporting, Inc. 1378 Cape Saint Claire Road Annapolis, MD 21409 (410) 974-0947 10 1 DR. LANGE: Good morning, Jim. 2 Dr. Connor. 3 DR. O'CONNOR: Good morning, I'm Chris O'Connor. I'm an affiliate physician by 4 training and currently, I'm the president of the Inova Heart and Vascular Institute, which is 5 an independent academic health system in Northern Virginia. 6 DR. LANGE: Good morning, Chris. 7 And now Dr. Jason Connor. 8 DR. CONNOR: I'm Jason Connor, a statistician at ConfluenceStat, Assistant Professor 9 of Medical Education at the University of Central Florida College of Medicine. 10 DR. LANGE: Thanks for joining us, Jason. 11 Dr. Brindis. 12 DR. BRINDIS: Hi, I'm Ralph Brindis. I'm a Clinical Professor of Medicine at UCSF, a 13 career in general cardiology and interventional cardiology, and also have a role with the 14 National Cardiovascular Data Registry of the American College of Cardiology. 15 DR. LANGE: Thank you, Ralph, for joining us. 16 Dr. Allen.