From Research to Clinic: Addressing Ethical and Policy Challenges Facing the Gene Therapy Ecosystem

PROJECT SUMMARY The U.S. Food and Drug Administration has approved gene therapies for several rare inherited diseases and blood cancers, and hundreds of clinical trials are in progress testing the safety and effectiveness of gene therapies for rare and ultra-rare disorders, various cancers, and complex neurological diseases. For patients

with rare and serious or debilitating disorders for whom existing treatment options are limited or do not work, the approved gene therapies and the promise of others are encouraging signs that new treatment options are emerging. Yet the translational gene therapy ecosystem faces several interrelated challenges: 1) obtaining

sufficient evidence of safety/effectiveness from clinical trials to justify FDA approval; 2) establishing cost and payer coverage policies so patients have access to affordable treatments; and 3) generating sufficient safety and effectiveness evidence of approved gene therapies when used in the clinical setting. The proposed project

will investigate how gene therapy challenges and associated ethical and policy issues that exist within the translational gene therapy ecosystem are characterized and being addressed. We will 1) analyze documents from federal and state policymakers (the FDA, the Centers for Medicare and Medicaid Services, relevant state

Medicaid agencies, the U.S. Congress) and organizations that play a role in agenda setting and influencing public policy regarding the translational gene therapy ecosystem; 2) conduct a survey with physicians from four therapeutic domains (hematology, infectious disease, neurology, oncology); 3) conduct in-depth interviews with

experts from five domains (translational gene therapy research and development; the FDA drug-approval/post- marketing process; health policy/payer coverage; patient advocacy; bioethics/ELSI of genetics and genomics); and 4) develop a) issue/policy briefs, b) recommendations for addressing gene therapy challenges and

associated ethical and policy issues, and c) recommendations for future normative and empirical analysis of gene therapy challenges and associated ethical and policy issues. Innovative features of the proposed project include being framed by the premise that gene therapy challenges are interrelated and co-exist within a

complex translational science ecosystem; examining how physicians, various experts, and policymakers are grappling with gene therapy challenges; and applying a normative framework that draws on ideas and concepts from bioethics and political science. The proposed project will synthesize the findings from the

document/policy analysis, survey, in-depth interviews, and normative analysis of gene therapy challenges and associated ethical and policy issues to develop recommendations and issue/policy briefs that will 1) help stakeholders in the translational gene therapy ecosystem in their deliberations and decision-making about

addressing gene therapy challenges and associated ethical and policy issues, and 2) identify ethical and policy issues within the translational gene therapy ecosystem that warrant additional normative and empirical investigation by various stakeholders.