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FDA Antifungal Workshop Transcript, Thursday, August 4, 2020

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FDA Antifungal Workshop Transcript, Thursday, August 4, 2020 Meeting August 4, 2020 Page 1 1 UNITED STATES 2 FOOD AND DRUG ADMINISTRATION 3 ________________________________ 4 PUBLIC WORKSHOP 5 DEVELOPMENT CONSIDERATIONS OF ANTIFUNGAL DRUGS TO 6 ADDRESS UNMET MEDICAL NEED 7 ________________________________ 8 9 DATE: Thursday, August 4, 2020 10 TIME: 9:13 a.m. 11 LOCATION: Remote Proceeding - MD 12 Virtual Silver Spring, MD 20903 13 REPORTED BY: Janel Folsom, Notary Public 14 15 16 17 18 19 20 21 22 Job No. CS3856635 www.CapitalReportingCompany.com 202-857-3376 Meeting August 4, 2020 Page 2 Page 4 1 A P P E A R A N C E S 1 P R O C E E D I N G S 2 2 DR. JOHN FARLEY: This is John Farley 3 DR. JOHN FARLEY 3 checking audio. 4 DR. SUMATI NAMBIAR 4 COURT REPORTER: Sounds good. We can 5 DR. RADU BOTGROS 5 hear you. 6 DR. ERIN ZEITUNI 6 DR. JOHN FARLEY: Good. Shall I go 7 DR. THOMAS WALSH 7 ahead and start? 8 DR. JASON MOORE 8 COURT REPORTER: Yes, you can start 9 DR. WILLIAM HOPE 9 now. 10 DR. LAURA KOVANDA 10 DR. JOHN FARLEY: Okay. I’m very sorry 11 DR. YULIYA YASINSKAYA 11 for the delay, everyone. This is our first virtual 12 DR. KIEREN MARR 12 workshop here in the Office of Infectious Disease. 13 DR. JOHN REX 13 We’ve put in lots of preparation and weren’t quite 14 MATTHEW SCHUELER 14 counting on doing this in the middle of a tropical 15 DR. PETER PAPPAS 15 storm, but we’re hoping that the workshop goes 16 DR. CHERYL DIXON 16 smoothly today. In the event that you do lose 17 DR. AARON DANE 17 Internet, please just log back in and join us. 18 DR. ASPASIA KATRAGKOU 18 I see that Tom Walsh is already losing 19 DR. LUIS OSTROSKY-ZEICHNER 19 connections but rejoining us right now. I want to 20 DR. TOM CHILLER 20 welcome everybody this morning and thank particularly 21 DR. HELEN BOUCHER 21 the speakers for the time that they’ve invested in 22 DR. BAOYING LIU 22 preparing for this event. Page 3 Page 5 1 DR. MICHAEL HODGES 1 We’re here today to focus on the 2 DR. DAVID ANGULO 2 development of new therapies to address unmet medical 3 DR. TAYLOR SANDISON 3 need for the treatment of infections due to invasive 4 DR. GEORGE THOMPSON 4 molds and Candida auris. Discussions today will 5 DR. DAVID DENNING 5 include the current state and clinical trial design 6 DR. JOHN PERFECT 6 considerations for developing new therapies for these 7 DR. THOMAS PATTERSON 7 infections. 8 DR. KAREN HIGGINS 8 Fungal diseases with unmet need occur 9 DR. JOHN BENNETT 9 in people who live in or travel to certain areas. An 10 DR. SHAWN LOCKHART 10 example of that is Valley Fever, which will be our 11 11 focus tomorrow. And they also commonly affect people 12 12 with weakened immune systems, and an example of that 13 13 is Candida auris, which we’ll be focusing on later 14 14 today. 15 15 Similar to antibacterial drugs, 16 16 antifungal resistance can severely limit treatment 17 17 options. The science of preclinical development is 18 18 hard and it’s very important to establish feasible 19 19 clinical trial designs that will lead to interpretable 20 20 data. 21 21 Like antibacterial drugs, there are 22 22 significant financial challenges. The key to making 2 (Pages 2 - 5) www.CapitalReportingCompany.com 202-857-3376 Meeting August 4, 2020 Page 6 Page 8 1 progress is coming together as a community. 1 disease, resistance to existing therapies or 2 Government staffs, academic researchers, healthcare 2 intolerance to currently available treatments. 3 providers, patients and drug developers to frankly 3 This is certainly very encouraging, but 4 discuss the challenges and ideas for making progress 4 at the same time we do recognize that there are 5 together, and that’s our main goal and our focus 5 scientific and practical challenges that need to be 6 today. 6 addressed. We hope that in today’s workshop we will 7 Just a bit of housekeeping. We ask 7 be able to identify some solutions to the issues at 8 that folks speak clearly and stick to the time so that 8 hand, and also identify some key areas that we’ll need 9 we can stay on time today and have time for some good 9 for the discussion. 10 discussion. For the audience, the speaker slides, 10 As John has mentioned, you know, we 11 transcripts and recordings will be available on the 11 also recognize that there are several economic 12 public webpage in the coming days. 12 challenges that face the field of anti-infectious drug 13 So, at this point, I’m going to turn 13 development at large, which includes both anti­ 14 the program over to Sumati Nambiar and Erin Zeituni. 14 bacterials and antifungals. Unfortunately, it’s not a 15 Sumati is from our group at FDA and heads the Division 15 topic that we can address or cover in today’s 16 of Anti-Infectives, and Erin is from NIH and very 16 workshop. 17 involved with support for antifungal drug development. 17 It’s really important to keep in mind 18 So, we’ll ask them to start Session 1 at this point. 18 that general principles for antifungal drug 19 Thanks very much. 19 development are similar in many aspects to those for 20 DR. SUMATI NAMBIAR: Yeah, thank you, 20 antibacterial drug development. And over the last 21 John. I hope everybody can hear me okay. Good 21 decade and maybe decade and a half, we’ve made 22 morning and I would like to add my welcome and thank 22 significant progress with antibacterial drug Page 7 Page 9 1 you all for joining us for today’s workshop. We look 1 development and have clearly defined in scientifically 2 forward to a productive meeting and hope that today’s 2 sound approaches that are feasible for many clinical 3 discussions will set the stage for future 3 conditions that clinicians see. 4 conversations as we continue to work together as a 4 This was not an easy task. It was 5 community to advance the field of antifungal drug 5 achieved by engagement with stakeholders. Some of you 6 development. 6 on the call participated in those discussions. We 7 As John said, Dr. Zeituni from NIAID 7 also engaged in public-private partnerships and 8 and I will co-moderate the first session on the 8 exercised some regulated flexibility, all supported by 9 background of clinical and preclinical concentrations. 9 good scientific evidence. 10 I’ll start with the first talk -- I’ll cover regulated 10 There are many important lessons that 11 considerations from an FDA perspective. And then I’ll 11 we’ve learned from completed programs. Unfortunately, 12 also present on behalf of colleagues from PMDA, our 12 many of them also from field programs, which is not 13 Japanese regulators, who unfortunately couldn’t join 13 what we like to see but I think very important to keep 14 us for the workshop. So, with that, if I can have my 14 in mind that they teach us many important lessons. We 15 slides up? Thank you. 15 recognize the importance of those selections, the body 16 Over the last few years we’ve seen some 16 site of infection, and the role animal models of 17 increased interest in antifungal drug development. In 17 infection play, particularly in streamlined 18 addition to the standard indications as in Candidiasis 18 development programs that are designed to attract 19 and invasive aspergillosis, there’s also interest in 19 unmet medical need. 20 developing antifungal drugs for the less common molds, 20 Presently, there’s more work to be 21 and also for an unmet need population, which is 21 done. There is ongoing work in defining or using 22 variously defined either by the presence of refractory 22 novel endpoints. There’s also discussion around 3 (Pages 6 - 9) www.CapitalReportingCompany.com 202-857-3376 Meeting August 4, 2020 Page 10 Page 12 1 designing trials for difficult to study indications 1 that during the course of our discussion today, when 2 and also how to develop drugs for special populations, 2 we discuss alternate endpoints, I think we should keep 3 including children. All of these certainly have 3 in mind that endpoints that are selected for clinical 4 relevance to antifungal drug development as well. 4 trial should be well-defined and reliable. 5 And just to make sure that we’re all on 5 The clinical endpoint should be one 6 the same page, at the very high level, you know, we 6 that measures an effect on how a patient feels, 7 have two regulatory pathways. The traditional 7 functions or survives. If it’s a surrogate marker -­ 8 approval pathway is generally based on an endpoint 8 surrogate endpoint, it’s usually a marker such as a 9 that measures how a patient feels, functions or 9 laboratory measurement or a radiographic change that’s 10 survives. An accelerated approval is based on a 10 likely to predict clinical benefit but is not in 11 surrogate endpoint that is reasonably likely to 11 itself a measure of clinical benefit. 12 predict clinical benefit or on a clinical endpoint 12 So, today we’ll also have a lot of 13 that can be measured earlier than irreversible 13 discussion about the role of diagnostics and how they 14 morbidity or mortality.
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