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Developing Alpha-1 Antitrypsin Therapeutics

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Developing Alpha-1 Antitrypsin Therapeutics UNITED STATES FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE ALPHA‑1 FOUNDATION ALPHA‑1 ANTITRYPSIN THERAPEUTICS DEVELOPMENT WORKSHOP Bethesda, Maryland Monday, September 16, 2019 PARTICIPANTS: Welcome and Introductory Remarks: PETER MARKS, MD, Ph.D. Director, Center for Biologics Evaluation and Research Food and Drug Administration ALPHA-1 FOUNDATION Representative: MIRIAM O'DAY Chief Executive Officer Alpha‑1 Foundation Alpha‑1 Antitrypsin Deficiency and Augmentation Therapy: ROBERT SANDHAUS, MD, Ph.D. Professor of Medicine National Jewish Health The Alpha‑1 Foundation Scientific Infrastructure: CHARLIE STRANGE, MD Professor of Pulmonary and Critical Care Medicine Medical University of South Carolina MIRIAM O'DAY Chief Executive Officer Alpha‑1 Foundation Update and Summary of Alpha‑1 Therapeutics: ROSE PIERCE, MD Medical Officer, Division of Clinical Evaluation & Pharmacology/Toxicology Office of Tissues and Advanced Therapies Center for Biologics Evaluation and Research Food and Drug Administration PARTICIPANTS (CONT'D): New Approaches to Clinical Trials: JOHN SCOTT, Ph.D. Director, Division of Biostatistics Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research Food and Drug Administration The Patient Journey: PEGGY IVERSON Alpha‑1 Patient Novel Targets for Alpha‑1 Antitrypsin: ADAM WANNER, MD Professor of Medicine University of Miami School of Medicine Novel Therapeutic Approaches That Raise Levels of Alpha‑1 Antitrypsin: TERENCE R. FLOTTE, MD Professor of Medical Education The University of Massachusetts Medical School STEFAN MARCINIAK, Ph.D. Professor of Respiratory Science Cambridge Institute for Medical Research MARK BRANTLY, MD Professor of Medicine, Molecular University of Florida College of Medicine KLAUS WAGNER, MD, Ph.D. Chief Medical Officer Inhibrx CHARLOTTE McKEE, MD Vice President, CF Clinical Development Vertex Pharmaceuticals Incorporated PARTICIPANTS (CONT'D): Implications for Other Plasma‑Based Therapies: SENATOR RICK SANTORUM Patient Advocate Partner in Plasma Technologies Therapeutic Approaches to Liver Disease in AATD: JAMES HAMILTON, MD, MBA Vice President, Clinical Development Arrowhead Pharmaceuticals Clinical Endpoints and Biomarkers in COPD Trials: JEANINE D'ARMIENTO, MD. Ph.D. Professor of Medicine Columbia University CT Densitometry: KENNETH CHAPMAN, MD MSc Director, Asthma & Airway Center University Health Network And Professor of Medicine University of Toronto Panel Discussion: Current Needs in Alpha‑1 Antitrypsin Drug Development: PETER MARKS, MD, Ph.D., Moderator Director, Center for Biologics Evaluation and Research Food and Drug Administration Summary and Conclusion/Next Steps: PETER MARKS, MD, Ph.D. Director, Center for Biologics Evaluation and Research Food and Drug Administration * * * * * P R O C E E D I N G S (8:33 a.m.) DR. MARKS: Good morning, everyone. Thank you everyone who is here at NIH at the auditorium and thank you everyone who is joining us on the web today. I am Peter Marks, Director of the Center for Biologics and Evaluation and Research at FDA and I want to welcome you to the Alpha‑1 antitrypsin therapeutics development workshop. This is a workshop that is being co‑sponsored by the Center for Biologics and Evaluation Research at FDA, The National Heart Fund and Blood Institute at NIH and the Alpha‑1 Foundation. We are going to try to keep introductions relatively short. Something I once learned is that running the trains on time at a meeting like this counts a lot so we are going to try to do that. You'll see me making wild motions at speakers if they start to run over time. You'll see me with my hook if they really run overtime so if you ever see me get up and start approaching the stage as a speaker, it means you are really over time and that will be your cue to sum up. So just to do a few housekeeping remarks before I say a couple of opening remarks, for anyone who needs them, there are restrooms just outside the doors in the back on both sides. Lunch today, there will be box lunches out in the back just outside the doors. You can take them up to the first floor where there is some seating. We ask that you do not have any open containers in this auditorium, regardless of what's inside those containers. Thanks for honoring that. And with that said, I just want to thank everyone for taking the time today. We have a really nice turnout from industry, from academics and patients as well so we are very happy to have this workshop. I think from the FDA perspective, one of the really interesting things and I think it will be a really great discussion to have today is that Alpha‑1 antitrypsin deficiency represents kind of a model disease where the end points are quite challenging to get at in studies and yet it's really a model for any number of diseases where we have to find ways to do clinical development efficiently to come and help patients so we are really looking forward to discussions today. We have a wide range of different topics and a transcript is being made of today's discussions, so you'll be able to refer to it after the meeting and I just want to thank you again for coming today. I am going to introduce Dr. James Kiley from NHLBI to say a couple of opening remarks and then Miriam O'Day from the Alpha‑1 Foundation will say some opening remarks and we will try to keep things moving very much on time or ahead of schedule. We know we have a package and we'll get through it. Thanks very much. (Applause) DR. KILEY: Okay, well I don't want to get on Peter's bad side just to get started and get him up and activated here right at the beginning but let me just extend a warm welcome to all of you from the NIH. You are on the main campus of NIH, if you haven't figured that out and we are very, very pleased to have an opportunity to co‑host this event, this meeting, with Alpha‑1 and with the FDA. It's a really important meeting. I think one of the first challenges, whenever you come up with a topic area for a meeting is to bring all the relevant stakeholders together and so we've made a really great first stride towards doing that, great attendance here. I see a lot of familiar faces but a lot of people that we don't know and that's really even better because now we can bring together a critical mass of people to address this topic and this is a critically important area. Looking for advances in how do we bring new therapy forward. I want to say for Alpha‑1 but also for lung diseases as a whole. National Heartland and Blood Institute, Division of Blood Diseases has had a long history of supporting research in this area. Not just COPD but certainly around Alpha‑1 antitrypsin deficiency. We would like to be able to continue that so we look forward to hearing the dialog, the exchange and all the information that may come from this and what I sort of urge you to do is to not lose sight of the fact that if there is research, if there are questions, if there are hypotheses that still require some additional data, more answers, it's important that we hear those because that's our lane, that's our swim lane, the research end of this. So we are certainly very, very pleased to partners with FDA, to talk with all of you, to see you here, to hear the recommendations from this and hopefully there will be some follow up that will occur, whether it's at the FDA regulatory phase or whether it's really at the phase of identifying the research and bringing those forward so that we can have a role to continue to support it. We'd like to begin to sort of think about cures. We'd like to be able to think about where we can really invest and advance the science so we can begin to start talking about cures and not so much palliative approaches. So, again, thank you all for coming. We are very, very pleased to see you all here. I now it's a very busy time for all of you. You've taken time out of your schedule to come here and participate in this, so we thank you very much. Please feel free to be open with your comments. I know you're in a formal setting here; you're in NIH but this is a time that all of you should be speaking up and telling us what you are thinking about in terms of this space. So again, warm welcomes, thank you. Hopefully you'll have a really productive day. We'll be here most of the day and we look forward to hearing the recommendations so thanks again. (Applause) MS. O'DAY: Good morning. I am absolutely thrilled to be here and to be in full partnership with FDA and NHLBI and I want to thank Dr. Marks specifically for the invitation to have this workshop and to Dr. Kiley in NHLBI for supporting us. You know, today is a day that could have great impact on patients with Alpha-1 antitrypsin deficiency. This is a rare, orphan disease. There are about 10,000 individuals who are identified and it's thrilling that we are here with our industry partners, with researchers, with physicians, with the government and also with patients to be able to have a thorough discussion about next generation and new therapies.
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