Enabling Precision Medicine:
The Role of Genetics in Clinical Drug Development
March 8, 2017
Keck Center of the National Academies
500 Fifth Street, NW Room 100
Washington, DC 20001
Statement of Task
The current drug development process faces challenges of efficiency and overall sustainability due in part to high research costs, lengthy development timelines, and late-stage drug failures. Novel clinical trial designs that target genetically identified participants represent a potentially disruptive paradigm shift that could reduce overall health care costs associated with drug development, improve patient outcomes, and further realize the goals of precision medicine. An ad hoc committee will plan and conduct a 1-day public workshop that will examine and discuss successes, challenges, and best practices for effectively using genetic information in the design and implementation of clinical trials to support the development of precision medicines, including exploring the potential advantages and disadvantages of such trials across a variety of disease areas. Topics covered could include strategies for including genetically focused populations in clinical trial
design, logistical challenges in conducting genetics-based clinical trials, and mechanisms for engaging with and educating potential trial participants. Discussions will be held among a broad array of stakeholders, which may include patients, academic researchers, health care providers, and representatives from the biopharmaceutical sector.
- To explore how clinical trials with genetically identified participants can enable more efficient and effective drug development and advance precision medicine.
- To highlight ongoing genetics-based clinical trials across a variety of diseases, examining best practices and lessons learned.
- To learn about the logistical challenges and successes associated with genetics-based clinical trial design.
- To examine possible mechanisms to engage participants and improve enrollment into clinical trials based on genetic characteristics.
The planning committee will develop the workshop agenda, will select and invite speakers and discussants, and may moderate the discussions. The proceedings of the workshop will be prepared by a designated rapporteur in accordance with institutional policy and procedures.
|8:30 a.m.||Opening Remarks|
STEVEN GALSON, Co-Chair of the Forum on Drug Discovery, Development, and Translation
Senior Vice President, Global Regulatory Affairs and Safety Amgen Inc.
GEOFFREY GINSBURG, Co-Chair of the Roundtable on Genomics and Precision Health
Director, Duke Center for Applied Genomics and Precision Medicine; Professor of Medicine, Pathology, and Biomedical Engineering
Duke University Medical Center
|8:35 a.m.||Charge to the Speakers and Participants|
LAURA NISENBAUM, Workshop Co-Chair
Advisor, Chorus Clinical Development
Eli Lilly and Company
SESSION I: OVERARCHING CONSIDERATIONS FOR IMPLEMENTING SUCCESSFUL GENETICS-BASED DRUG DEVELOPMENT
- Discuss the perspective of patients with regard to the use of genetic data in clinical drug development.
- Consider challenges and possible solutions associated with the development and use of biomarkers or genetic tests for molecularly targeted therapies.
- Explore issues that pertain to the regulatory pathway for genetic tests and biomarkers used in clinical drug development.
|Moderator:||LAURA NISENBAUM, Advisor, Chorus Clinical Development, Eli Lilly and Company|
|8:45 a.m.||Accelerating the Pace of Progress in Genetics-Based Drug Development: The Perspective of a Patient and Patient Advocate|
|President and Founder|
|9:00 a.m.||Clarifying Questions|
|9:10 a.m.||Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies: Recommendations from a National Academies Consensus Study|
|Chief Medical Officer|
|9:30 a.m.||Clarifying Questions|
|9:40 a.m.||Navigating the Regulatory Pathway for Genetic Tests and Biomarkers for Clinical Drug Development|
|Associate Director for Genomics and Targeted Therapy|
|Center for Drug Evaluation and Research|
|U.S. Food and Drug Administration|
|10:00 a.m.||Clarifying Questions|
SESSION II: CASE STUDIES IN PRECISION DRUG DEVELOPMENT
- Explore recent examples of precision drug development in order to identify lessons that can be applied across disease fields.
- Examine clinical development plans for precision medicines, including
- using our understanding of the underlying biology to inform trial design and product development;
- effects on research costs and timeline; and
- patient recruitment and stratification.
|Moderator:||RICHARD SCHILSKY, Chief Medical Officer, American Society of Clinical Oncology|
|10:25 a.m.||Lung Master Protocol (Lung-MAP): A Biomarker-Driven Protocol for Accelerating Therapeutic Development for Squamous Cell Lung Cancer|
Professor of Medical Oncology; Associate Director for Translational Research
Yale Cancer Center
|10:40 a.m.||STARTRK-2 Clinical Trial: A Basket Study of Entrectinib for the Treatment of Solid Tumors with Specific Gene Rearrangements|
|Chief Operating Officer|
|10:55 a.m.||Genetic Testing and Clinical Drug Development for Spinal Muscular Atrophy|
|Associate Medical Director|
|11:10 a.m.||Using Genetics in Clinical Trials for Mitochondrial Diseases|
Associate Professor of Pediatrics, University of Pennsylvania
Director, Mitochondrial Disease Clinical Center, Children’s Hospital of Philadelphia
|11:25 a.m.||Panel Discussion with Audience and Speakers|
|12:10 p.m.||Working Lunch|
SESSION III: INTEGRATING GENETICS INTO THE DRUG DEVELOPMENT PATHWAY FOR COMPLEX DISEASES
- Illuminate novel ways to apply genetics/genomics discoveries into clinical development plans for complex diseases as a way to increase efficiency and improve outcomes.
- Survey innovative ways to engage participants in precision clinical trials, including communication, outreach, and education-based initiatives, with additional attention paid to increasing the diversity of such trials.
- Discuss additional logistical challenges associated with the execution of a successful genetics-based clinical trial for a complex disease, including
- techniques for patient stratification, including considerations for employing genetic risk scores; and
- timelines for developing molecularly targeted therapies, including trial execution.
|Moderator||RUSS ALTMAN, Professor, Stanford University|
|1:00 p.m.||Patient Perspective on Genetics-Enabled Drug Development|
|THERESA V. STRONG|
|Director of Research Programs|
|Foundation for Prader-Willi Research|
|1:15 p.m.||Clarifying Questions|
|1:20 p.m.||Potential Advantages and Pitfalls to Using Genetics in Drug Development for Complex Diseases|
|Head of Genetics|
|1:35 p.m.||Clarifying Questions|
|1:40 p.m.||Challenges in Leveraging GWAS Findings During Drug Development: A Case Study|
Head of Clinical Pharmacogenomics and Operations
|Merck & Co., Inc.|
|1:55 p.m.||Clarifying Questions|
|2:00 p.m.||Updates and Strategies from the TAILOR-PCI Trial|
|Professor and Vice Chair of Research, Department of Medicine University of Toronto|
|2:15 p.m.||Clarifying Questions|
|2:20 p.m.||Panel Discussion with Audience and Speakers|
|G. SCOTT CHANDLER|
Vice President and Global Head of Licensing and Early Development Safety
|Banner Alzheimer’s Institute|
Massachusetts Institute of Technology Sloan School of Management
|L. KEOKI WILLIAMS|
Associate Director, Center for Health Policy and Health Services Research
|Henry Ford Health System|
SESSION IV: FINDING INNOVATIVE WAYS TO INTEGRATE GENETICS RESEARCH INTO THE DRUG DEVELOPMENT PROCESS
- Explore innovative, “outside-the-box” ideas for genetics-based clinical trials that could make the therapeutic development pathway more efficient.
|Moderator:||BRAY PATRICK-LAKE, Director of Stakeholder Engagement, Duke University, Clinical and Translational Science Institute|
|3:35 p.m.||Return on Investment from Patient Input on Development|
|Director, Clinical Innovation|
|Pfizer Worldwide Research and Development|
|3:55 p.m.||SaME Therapeutics: Grouping Rare Disease Patients by Shared Molecular Etiology to Accelerate Clinical Trials|
|P. J. BROOKS|
|Program Director, Division of Clinical Innovation|
|National Center for Advancing Translational Sciences|
|4:15 p.m.||New Targets, New Modalities, New Challenges—The Inconvenient Path of Human Genetics in Drug Discovery|
|Vice President and Head of Translational Medicine|
|Merck & Co., Inc.|
|4:35 p.m.||Panel Discussion with Audience and Speakers|
SESSION V: LOOKING FORWARD—RECAP AND CONCLUSIONS
|Moderator:||ESTEBAN BURCHARD, Professor, University of California, San Francisco|
|5:05 p.m.||Summary of Key Points—Session I|
|LAURA NISENBAUM, Workshop Co-Chair|
|Advisor, Chorus Clinical Development|
|Eli Lilly and Company|
|5:10 p.m.||Summary of Key Points—Session II|
|Director, Precision Medicine|
|5:15 p.m.||Summary of Key Points—Session III|
RUSS ALTMAN, Co-Chair of the Forum on Drug Discovery, Development, and Translation
Professor of Bioengineering, Genetics, Medicine, and (by courtesy) Computer Science
|5:20 p.m.||Summary of Key Points—Session IV|
|Director, Stakeholder Engagement|
Duke University, Clinical and Translational Science Institute
|5:25 p.m.||Final Remarks|
ESTEBAN BURCHARD, Workshop Co-Chair
Professor and Vice Chair, Department of Bioengineering and Therapeutic Sciences and Medicine
University of California, San Francisco