Development of New Tuberculosis Drug Regimens
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TB Workshop July 19, 2017 Page 1 1 FOOD AND DRUG ADMINISTRATION (FDA) 2 3 4 5 DEVELOPMENT OF NEW TUBERCULOSIS DRUG REGIMENS 6 SCIENTIFIC AND CLINICAL DESIGN CONSIDERATIONS 7 PUBLIC WORKSHOP 8 9 10 Wednesday, July 19, 2017 11 12 13 White Oak Campus 14 10903 New Hampshire Avenue 15 Silver Spring, Maryland 20903 16 17 18 19 20 Reported by: Michael Farkas 21 Capital Reporting Company 22 www.CapitalReportingCompany.com 202-857-3376 TB Workshop July 19, 2017 Page 2 Page 4 1 PARTICIPANTS 1 TABLE OF CONTENTS 2 Cathy Bansbach, PhD, Bill & Melinda Gates 2 AGENDA ITEM Page 3 Foundation, Seattle, WA 3 Introductory Remarks/Panel Introduction - Ed Cox 6 4 Dakshina Chilukuri, PhD, OCP, CDER, FDA 4 LANDSCAPE AND PRECLINICAL APPROACHES TO INFORM 5 Edward Cox, MD, OAP, CDER, FDA 5 CLINICAL CANDIDATES FOR TB COMBINATION REGIMENS 6 John Farley, MD, OAP, CDER, FDA 6 Co-chairs John Farley, Philip LoBue 7 Lawrence Geiter, PhD, Otsuka, Rockville, MD 7 Landscape and Important Challenges 8 Steve Gitterman, MD, PhD, OIR, CDRH, FDA 8 Philip LoBue 16 9 Debra Hanna, PhD, Critical Path Institute, Tucson, 9 Cathy Bansbach 31 10 AZ 10 Need for Accessibility of New TB Drug 43 11 Karen Higgins, Sc.D., OAP, CDER, FDA 11 Regimens: Patient and Community Perspective 12 David Hughes, MD, Novartis Pharma AG, Basel, 12 Erica Lessem 13 Switzerland 13 What's New in Preclinical Tools Used for 65 14 Dmitri Iarikov, MD, DAIP, OAP, FDA 14 Evaluation of New Components of TB Regimens 15 Erica Lessem, MPH, Treatment Action Group, New 15 Eric Nuermberger 16 York City, NY 16 Assessing TB Drug Pharmacokinetics in 96 17 Christian Lienhardt, MD, WHO, Geneva, Switzerland 17 Clinical Studies - Charles Peloquin 18 Philip LoBue, MD, CDC, Atlanta, GA 18 TB Biomarkers and Clinical Utility 115 19 Payam Nahid, MD, UCSF, San Francisco, CA 19 Payam Nahid 20 Sumathi Nambiar, MD, DAIP, OAP, FDA 20 New Approaches to TB Diagnostics 139 21 Eric Nuermberger, MD, Johns Hopkins University 21 Marco Schito 22 School of Medicine, Baltimore, MD 22 CPTR Role in Facilitating TB Drug 153 Page 3 Page 5 1 Sheral Patel, MD, DAIP, OAP, FDA 1 AGENDA ITEM PAGE 2 Charles Peloquin, PharmD, Emerging Pathogens 2 Development - Debra Hann 3 Institute, University of Florida, Gainsville, FL 3 Public Presentations 168 4 Patrick Phillips, PhD, UCSF, San Francisco, CA 4 Panel Discussion 173 5 Marco Schito, PhD, Critical Path Institute, 5 NEW CLINICAL APPROACHES FOR TB REGIMEN DEVELOPMENT 6 Tucson, AZ 6 Session Co-Chairs - Sumathi Nambiar, Mel Spigelman 7 Mel Spigelman, MD, Global Alliance for TB Drug 7 Regulatory Overview - Karen Higgins 189 8 Development, New York, NY 8 New Approaches to TB Drug Development: 9 Jeffrey Starke, MD, Baylor College of Medicine, 9 Developer and Industry Perspective 10 Houston, TX 10 Mel Spigelman 207 11 Joe Toerner, MD, DAIP, OAP, FDA 11 Charles Wells 224 12 Andrew Vernon, MD, CDC, Atlanta, GA 12 Tuberculosis Trials Consortium: CDC 13 Charles Wells, MD, Sanofi, Bridgewater, NJ 13 Experience - Andrew Vernon 244 14 Yuliya Yasinskaya, MD, DAIP, OAP, FDA 14 Trial Design Considerations in Pediatric 260 15 15 Populations - Jeffrey Starke 16 16 Lessons Learned from Completed TB Trials 280 17 17 and Implications for Future Trials 18 18 Christian Lienhardt 19 19 Panel Discussion 304 20 20 Closing Remarks 334 21 21 Adjourn 335 22 22 2 (Pages 2 - 5) www.CapitalReportingCompany.com 202-857-3376 TB Workshop July 19, 2017 Page 6 Page 8 1 P R O C E E D I N G S 1 And lots of credit goes to the TB community, including 2 DR. COX: I wanted to welcome everybody today 2 the drug developers, the philanthropists, scientists 3 to our TB drug development workshop. We will be 3 from all sectors, patient advocacy groups, folks in 4 talking a lot about a regimen development and having 4 government, both here in the US and abroad, and 5 some discussions around all that. I really do 5 nongovernmental organizations that remain dedicated to 6 appreciate everybody making the time to join us here 6 the work of developing new therapies for TB and caring 7 today. 7 for patients with TB. 8 And, first, let me just start off with some 8 And, at least in my view, as I reflect on the 9 logistics, just so we can plan ahead a little bit. You 9 area, I think one of the things that has made things so 10 may have noticed as you walked in, there is a window 10 successful in this area is really the attention to 11 just beyond these large rooms and it is where lunch is 11 sound scientific principles and the dedication to work 12 served. And so, if you can order ahead of time, so if 12 in this field. We all recognize that this is an area 13 we can get your orders in, say, by about 10:30 in the 13 where there are unmet needs and that we can exercise 14 morning, that can help a little bit with the lunchtime 14 flexibility and balance benefits and risks. But I 15 crunch, because then they're all prepared for serving 15 think what allows us to do that is that underlying this 16 the individuals. So, it's always important to make 16 foundation of flexibility is the sound science that is 17 sure that everybody gets fed during lunchtime, so just 17 going on in the field, and that's great. 18 check with that window, if you can. Hopefully, we'll 18 If we can think back to TB therapies, the last 19 be able to do that during the break. The folks over 19 new TB drug approval here in the US was bedaquiline for 20 there should be expecting people to come out. 20 MDR-TB that was approved in late 2012. But for those 21 Now, moving on to the topic for today. I 21 that follow the field, there has also been a lot of 22 mean, as folks know here, probably better than I, the 22 other important activity that has been going on out Page 7 Page 9 1 TB issue with global burden of disease really is 1 there reported in journal articles and press releases, 2 phenomenal, a tremendous cause of morbidity and 2 and such. And so, we thought it would be a good 3 mortality with 10.4 million new cases of TB reported 3 opportunity to get the field together to discuss some 4 worldwide by the WHO. With 2.2 million cases in 4 of the important progress that has been made in the 5 patients living with HIV, and estimates of 480,000 5 field and share that more broadly. That's one of the 6 cases of MDR-TB in 2015. So, the burden of disease is 6 reasons, too, why we'll talk some about regimen 7 tremendous. 7 development. 8 We also know, too, folks working this area 8 And we're grateful, too, for the field's 9 know how particularly challenging it is to develop new 9 general willingness to describe ongoing development 10 therapies for TB, and the treatments are long, require 10 programs and have the chance to hear from the groups 11 multiple drug therapy. And it's really not an area 11 that are involved in this work. We'll hear some 12 that is economically attractive for drug development. 12 preliminary results from clinical trials to date, and I 13 While we know the burden of disease is large, the areas 13 think we'll all benefit by hearing and learning from 14 of the world where the burden of disease is largest are 14 their experiences. 15 not ones that have resources. And typically, it's low 15 And then if you'll look at the agenda, too, 16 and middle-income countries where there is limited 16 today, you'll see that we're going to span a range of 17 resources to be able to afford treatment and access to 17 topics over a really fairly packed agenda. We'll start 18 care can oftentimes be challenging. 18 out with hearing some about the current TB landscape 19 But, really, despite these challenges, as I 19 patient needs, and then move on to preclinical and 20 look around the room and think about the 20 clinical development with a focus on TB regimen 21 accomplishments of this group, the folks that have been 21 development. And then to guide our discussion over the 22 involved in TB work, I mean, it really is remarkable. 22 course of the day, following the talks in the morning 3 (Pages 6 - 9) www.CapitalReportingCompany.com 202-857-3376 TB Workshop July 19, 2017 Page 10 Page 12 1 and the talks in the afternoon, we have a series of 1 I'm the deputy director for safety in the Division of 2 questions that we'll try and cover during panel 2 Anti-Infective Products at CDER, FDA. 3 discussions, both in the morning and the afternoon. I 3 DR. NAHID: Good morning. My name is Payam 4 look forward to hearing those discussions, and I hope 4 Nahid. I'm at the University of California-San 5 everybody has a chance to engage in the panel 5 Francisco. I am a TB clinical trialist working with 6 discussions. 6 the CDC TB trials consortium. 7 Today is a workshop, which is different than 7 DR.