1 1 FOOD AND DRUG ADMINISTRATION 2 CENTER FOR DRUG EVALUATION AND RESEARCH 3 4 5 6 ANTIMICROBIAL DRUGS ADVISORY COMMITTEE MEETING 7 (AMDAC) 8 9 10 Thursday, April 25, 2019 11 8:30 a.m. to 4:36 p.m. 12 13 14 15 16 17 Tommy Douglas Conference Center 18 1000 New Hampshire Avenue 19 Silver Spring, Maryland 20 21 22 A Matter of Record (301) 890-4188 2 1 Meeting Roster 2 DESIGNATED FEDERAL OFFICER (Non-Voting) 3 Lauren Tesh Hotaki, PharmD, BCPS 4 Division of Advisory Committee and Consultant 5 Management 6 Office of Executive Programs, CDER, FDA 7 8 ANTIMICROBIAL DRUGS ADVISORY COMMITTEE MEMBERS 9 (Voting) 10 Lindsey R. Baden, MD 11 (Chairperson) 12 Director of Clinical Research 13 Division of Infectious Diseases 14 Brigham and Women’s Hospital 15 Director, Infectious Disease Service 16 Dana-Farber Cancer Institute 17 Associate Professor, Harvard Medical School 18 Boston, Massachusetts 19 20 21 22 A Matter of Record (301) 890-4188 3 1 CAPT Timothy H. Burgess, MD, MPH, FACP 2 Director 3 Infectious Disease Clinical Research Program 4 Preventative Medicine & Biostatistics 5 Uniformed Services University of the Health 6 Sciences 7 Bethesda, Maryland 8 9 Nina M. Clark, MD 10 Professor 11 Stritch School of Medicine 12 Clinical Division Director, Infectious Diseases 13 Director, Transplant Infectious Disease Program 14 Loyola Medical Center 15 Maywood, Illinois 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 4 1 Dean A. Follmann, PhD 2 Assistant Director of Biostatistics 3 Chief Biostatistics Research Branch 4 National Institute of Allergy and 5 Infectious Diseases 6 National Institutes of Health 7 Bethesda, Maryland 8 9 Michael Green, MD, MPH 10 Professor of Pediatrics, Surgery and Clinical & 11 Translational Science 12 University of Pittsburgh School of Medicine 13 Division of Infectious Diseases 14 Director, Antimicrobial Stewardship & Infection 15 Prevention 16 Co-Director, Transplant Infectious Diseases 17 Children’s Hospital of Pittsburgh 18 Pittsburgh, Pennsylvania 19 20 21 22 A Matter of Record (301) 890-4188 5 1 Barbara M. Gripshover, MD 2 Associate Professor of Medicine 3 University Hospitals Cleveland Medical Center 4 Case Western Reserve University 5 Division of Infectious Diseases and HIV Medicine 6 Cleveland, Ohio 7 8 Ighovwerha Ofotokun, MD, MSc 9 Professor of Medicine 10 Division of Infectious Diseases 11 Department of Medicine 12 Emory University School of Medicine 13 Atlanta, Georgia 14 15 George K. Siberry, MD, MPH 16 Medical Officer 17 Adult Clinical Branch, Office of HIV/AIDS 18 S/GAC Senior Technical Advisor for Pediatrics 19 U.S. Agency for International Development 20 Arlington, Virginia 21 22 A Matter of Record (301) 890-4188 6 1 Sankar Swaminathan, MD 2 Professor and Chief, Division of Infectious 3 Diseases 4 Department of Internal Medicine 5 University of Utah School of Medicine 6 Salt Lake City, Utah 7 8 Peter Joseph Weina, PhD, MD 9 Colonel, Medical Corps, US Army 10 Branch Chief, Research Regulatory Oversight Office 11 Office of the Under Secretary of Defense 12 (Personnel and Readiness) 13 Defense Health Headquarters 14 Falls Church, Virginia 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 7 1 ANTIMICROBIAL DRUGS ADVISORY COMMITTEE MEMBERS 2 (Non-Voting) 3 Nicholas A. Kartsonis, MD 4 (Industry Representative) 5 Sr. Vice President 6 Infectious Diseases & Vaccines, Clinical Research 7 Merck Research Laboratories 8 North Wales, Pennsylvania 9 10 TEMPORARY MEMBERS (Voting) 11 Judith Baker, DrPH, MHSA 12 (Consumer Representative) 13 Public Health Director 14 Western States Regional Hemophilia Network 15 Pacific Sickle Cell Regional Collaborative 16 Center for Inherited Blood Disorders 17 Adjunct Assistant Professor 18 UCLA-Division of Pediatric Hematology/Oncology 19 Los Angeles, California 20 21 22 A Matter of Record (301) 890-4188 8 1 Catherine M. Brown, DVM, MSc, MPH 2 State Epidemiologist and State Public Health 3 Veterinarian 4 Bureau of Infectious Disease and Laboratory 5 Sciences 6 Massachusetts Department of Public Health 7 National Association of State Public Health 8 Veterinarian’s Compendium of Animal Rabies 9 Control and Prevention, Co-chair 10 Boston, Massachusetts 11 12 James A. Ellison, PhD 13 (speaker and temporary member) 14 Microbiologist 15 Poxvirus and Rabies Branch 16 Division of High-Consequence Pathogens and 17 Pathology 18 National Center for Emerging and Zoonotic 19 Infectious Diseases 20 Centers for Disease Control and Prevention 21 Atlanta, Georgia 22 A Matter of Record (301) 890-4188 9 1 Alexia Harrist, MD, PhD 2 State Health Officer and State Epidemiologist 3 Chief, Public Health Sciences Section 4 Public Health Division 5 Wyoming Department of Health 6 Cheyenne, Wyoming 7 8 Susan M. Moore, PhD, MS, HCLD(ABB), MT(ASCP)SBB 9 Clinical Assistant Professor/Rabies Laboratory 10 Director 11 Kansas State Veterinary Diagnostic Laboratory 12 College of Veterinary Medicine 13 Kansas State University 14 Manhattan, Kansas 15 16 Laura D. Porter, MD 17 (Patient Representative) 18 Cheverly, Maryland 19 20 21 22 A Matter of Record (301) 890-4188 10 1 FDA PARTICIPANTS (Non-Voting) 2 John Farley, MD, MPH 3 Deputy Director 4 Office of Antimicrobial Products (OAP) 5 Office of New Drugs (OND) 6 CDER, FDA 7 8 Debra Birnkrant, MD 9 Director 10 Division of Antiviral Products (DAVP) 11 OAP, OND, CDER, FDA 12 13 Jeffrey Murray, MD, MPH 14 Deputy Director 15 DAVP, OAP, OND, CDER, FDA 16 17 Stephanie Troy, MD 18 Medical Officer 19 DAVP, OAP, OND, CDER, FDA 20 21 22 A Matter of Record (301) 890-4188 11 1 Tanvir Bell, MD, FACP, FIDSA 2 Medical Officer 3 DAVP, OAP, OND, CDER, FDA 4 5 Damon Deming, PhD 6 Clinical Virology Reviewer 7 DAVP, OAP, OND, CDER, FDA 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 12 1 C O N T E N T S 2 AGENDA ITEM PAGE 3 Call to Order and Introduction of Committee 4 Lindsey Baden, MD 14 5 Conflict of Interest Statement 6 Lauren Tesh Hotaki, PharmD, BCPS 19 7 FDA Opening Remarks 8 Jeffrey Murray, MD 22 9 FDA Presentations 10 Background on Rabies and Why 11 Monoclonal Antibodies (mAbs) are Being 12 Developed for Rabies PEP 13 Tanvir Bell, MD, FACP, FIDSA 26 14 Neutralizing Activity of Anti-Rabies 15 Virus Antibodies in Cell Culture 16 Damon Deming, PhD 42 17 Speaker Presentation 18 Use of Animal Models in Rabies 19 Product Development 20 James Ellison, PhD 55 21 22 A Matter of Record (301) 890-4188 13 1 C O N T E N T S (continued) 2 AGENDA ITEM PAGE 3 FDA Presentations (continued) 4 Clinical Trials to Evaluate Rabies mAb 5 Cocktails as a Component of 6 Post-Exposure Prophylaxis and a 7 Proposed Development Pathway 8 Stephanie Troy, MD 64 9 Clarifying Questions 90 10 Questions to the Committee and Discussion 221 11 Adjournment 340 12 13 14 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 14 1 P R O C E E D I N G S 2 (8:30 a.m.) 3 Call to Order 4 Introduction of Committee 5 DR. BADEN: Good morning. I'd like to call 6 this meeting to order. I would first like to 7 remind everyone to please silence your cell phones, 8 smartphones, and any other devices if you've not 9 already done so. I would also like to identify the 10 FDA press contact, Allison Hunt. If you are 11 present, please stand. Allison will be joining us 12 later. 13 My name is Dr. Lindsey Baden. I'm the 14 chairperson of the Antimicrobial Drugs Advisory 15 Committee, and I will be chairing this meeting. I 16 will now call this meeting to order. We'll start 17 by going around the table and introduce ourselves. 18 We'll start with the FDA to the far left. 19 DR. FARLEY: Good morning. John Farley, 20 deputy director of the Office of Antimicrobial 21 Products, CDER, FDA. 22 DR. BIRNKRANT: Good morning. Debbie A Matter of Record (301) 890-4188 15 1 Birnkrant, director of Division of Antiviral 2 Products, FDA. 3 DR. MURRAY: Jeff Murray, deputy, Division 4 of Antiviral Products, FDA. 5 DR. TROY: Stephanie Troy, clinical 6 reviewer, Division of Antiviral Products, FDA. 7 DR. BELL: Tanvir Bell, medical officer, 8 Division of Antiviral Products, FDA. 9 DR. DEMING: Damon Deming, virology 10 reviewer, Division of Antiviral Products, FDA. 11 DR. SWAMINATHAN: Sankar Swaminathan, 12 University of Utah. 13 DR. SIBERRY: Good morning. George Siberry, 14 medical officer, USAID. 15 DR. GRIPSHOVER: Barb Gripshover, infectious 16 disease, Case Western Reserve University. 17 DR. GREEN: Michael Green, pediatric 18 infectious disease, Children's Hospital Pittsburgh 19 and the University of Pittsburgh School of 20 Medicine. 21 DR. WEINA: Good morning. Peter Weina, 22 infectious disease physician with the Office of the A Matter of Record (301) 890-4188 16 1 Undersecretary of Defense. 2 DR. HOTAKI: Lauren Hotaki, designated 3 federal officer. 4 DR. BADEN: Lindsey Baden, infectious 5 diseases, Brigham and Women's Hospital, Dana-Farber 6 Cancer Institute, and Harvard Medical School in 7 Boston. 8 DR. CLARK: Nina Clark, infectious diseases, 9 Loyola University Medical Center, Maywood, 10 Illinois. 11 DR. FOLLMANN: Dean Follmann, biostatistics, 12 National Institute of Allergy and Infectious 13 Diseases. 14 DR. OFOTOKUN: Igho Ofotokun, Emory 15 University in Atlanta, adult infectious diseases. 16 CAPT BURGESS: Tim Burgess, adult infectious 17 diseases, Uniformed Services University and DoD's 18 infectious disease clinical research program. 19 DR. PORTER: Laura Porter, patient 20 representative.