Back in December, the U.S. Food and Drug Administration (FDA) granted its first approval for a gene therapy product, Spark Therapeutics’ Luxturna. According to the Alliance for Regenerative Medicine, as many as 50 more such treatments — addressing a diverse range of health problems from genetic, autoimmune, and heart diseases, to cancer and HIV/AIDS — could reach the marketplace in the next few years.
In June, FDA Commissioner Scott Gottlieb announced a comprehensive framework for the development, review and approval of gene therapies, which aims to advance the field while ensuring that new products meet the FDA’s “gold standard for safety and effectiveness.”
In July, as part of this framework, the FDA issued six detailed draft “Guidance” documents that help direct developers through preclinical and clinical studies and manufacturing efforts. Three documents deal with specific types of gene therapy products: treatments for hemophilia, rare diseases for both adults and children, and retinal disorders like Spark’s treatment for an inherited form of blindness. In addition to general considerations for clinical trial design, they provide product-specific recommendations. For example, the guidelines for hemophilia products — deficiencies of the clotting Factors VIII (Hemophilia A) and IX (Hemophilia B) — provide specific recommendations concerning the use of surrogate endpoints for pursuing accelerated approvals. The guidelines for rare diseases recommend working with the FDA to design development programs for indications with a very small patient population, where proving therapeutic efficacy may be complicated.
The remaining three documents relate to manufacturing issues and, compared to the 2008 guidelines, reflect both advances in the area as well as uncertainties and risks pertaining to the long-term duration of potential therapeutic benefits.
The FDA acknowledges that there is much yet to learn about gene therapies, such as how they work, how they can be produced consistently and administered safely, as well as their long-term efficacy and safety. The agency also acknowledges the need to accept some uncertainty over gene therapy products, stressing the importance of post-market clinical trials to help answer questions over durability and safety of response over time.