In response to the surge of cell and gene therapies in development, the U.S. Food and Drug Administration announced a plan to expand its staff dedicated to evaluating these therapies, issuing guidances, and increasing enforcement actions against companies that do not comply with the agency’s requests.

FDA Commissioner Scott Gottlieb and Director of the Center for Biologics Evaluation and Research Peter Marks said in a joint statement posted to the agency’s website that they anticipate receiving more than 200 new applications to begin clinical trials per year by 2020 for cell and gene therapies, adding to the more than 800 active applications currently on file with the agency.

“By 2025, we predict that the FDA will be approving 10 to 20 cell and gene therapy products a year based on an assessment of the current pipeline and the clinical success rates of these products,” they said.

While lamenting current constraints due to the government shutdown, the FDA hopes to add about 50 additional clinical reviewers to the group charged with overseeing the clinical investigation, development, and review of these therapeutic products.

They compared the acceleration of cell and gene therapy technology advancements to the development of antibody therapeutics 20 years ago.

“The activity reflects a turning point in the development of these technologies and their application to human health. It’s similar to the period marking an acceleration in the development of antibody drugs in the late 1990s, and the mainstreaming of monoclonal antibodies as the backbone of modern treatment regimens.”

They noted the importance of sound policy, promised to introduce additional new policy guidances in the coming year, and preview the policy agenda for these new technologies. The FDA will work with companies to help them use accelerated programs, including regenerative medicine advanced therapy designation and accelerated approval. Using these pathways allows gene therapies to get to market faster but they will also be subject to post-market follow-up studies to evaluate their durability and safety.

The agency is also planning a series of clinical guidance documents related to different areas of active product development. Clinical guidance documents to be advanced include ones for the development of gene therapy products for inherited blood disorders, recommendations on product development issues related to the development of gene therapy products for certain neurodegenerative diseases, and guidance to address how the accelerated approval pathway may be used when the target of the gene therapy product is an underlying monogenetic change that causes a serious disorder not addressed by available therapy.

The FDA leaders also plan guidance on the appropriateness of a traditional approach to drug development for gene therapies that create a genetic alteration aimed at treating the symptoms of a neurodegenerative disease, or potentially altering its course rather than curing the underlying condition.

They also discussed cell-based gene therapies using CAR-T cells and their safe manufacture, and plan to recommend parameters for how innovators can introduce advances in manufacturing that promote the more efficient development and application of CAR-T therapies without requiring costly new clinical investigations.

“One of our goals here is to allow for the development of clearer parameters for when minor manufacturing changes can be made that wouldn’t require additional bridging studies,” the FDA leaders said.

FDA also plans to issue guidance to propose an innovative trial design by which individual researchers can pool their clinical data after following a common manufacturing protocol, and thereby develop a more robust data set for purposes of applying for marketing approval.

“The idea here is to assist small sponsors, including academic investigators, who may not be of sufficient scale to conduct a clinical trial on their own, to band together with others similarly situated,” Gottlieb and Marks said.

Finally, the FDA also plans to ramp up enforcement actions against those that work outside regulatory compliance, especially those whose products pose significant safety concerns to patients. It will go after those who do not respond to FDA requests for dialogue.

In closing, the FDA leaders affirmed the promise of cell-based and gene therapy technologies for addressing some of the most intractable diseases. “But with their novelty, also comes new uncertainties and some unique, theoretical risks,” they said. “Our efforts are aimed at helping innovators proactively address these potential risks, while we outline a modern and efficient pathway for the continued development of these innovations.”


January 16, 2019
Photo: FDA Commissioner Scott Gottlieb