- Aiming to keep pace with the acceleration of cell and gene therapy research, the Food and Drug Administration plans to expand its clinical review staff, release a series of wide-ranging guidance documents and crack down on bad actors, two agency leaders said in a statement released Tuesday.
- FDA Commissioner Scott Gottlieb and Peter Marks, director of the Center for Biologics Evaluation and Research, said in a joint statement they anticipate more than 200 Investigational New Drug applications per year by 2020 for cell and gene therapeutic candidates, adding to a current total of more than 800 such filings. That will help lead to, they predict, 10 to 20 approvals each year for these treatments by 2025.
- The FDA's action plan "reflects a turning point in the development of these technologies and their application to human health," Gottlieb and Marks said, comparing to the 1990s, when monoclonal antibodies grew to become a key component of modern medicine.
So far, the FDA has approved only a handful of cell and gene therapies, including Spark Therapeutics' Luxturna (voretigene neparvovec), Gilead Sciences' Yescarta (axicabtagene ciloleucel) and Novartis' Kymriah (tisagenlecleucel). According to this statement, the agency's leaders see many more coming in the next few years.
The FDA will attempt to keep up with the cell and gene therapy field in three main ways: growing staff, issuing guidance and stepping up enforcement actions.
On the first, the agency's cell and gene therapy review group will add 50 clinical reviewers over time. These new hires, who will oversee clinical investigation, development and review, will expand that team by about 50%, Gottlieb tweeted.
Gottlieb and Marks also said industry should expect guidance from the agency on several related topics throughout this year.
One will focus on how companies should use accelerated approval to speed development of the complex treatments. Through this framework, gene therapies can get to market faster while the agency has more authority to require post-market studies.
"Since many of the risks associated with gene therapy products relate to questions about the product's durability and potential for rare instances of off-target effects, it may not be feasible to conduct pre-market trials that address all these theoretical risks in any reasonably sized study," the FDA leaders wrote.
Gottlieb and Marks said there would be guidance on which therapies should aim to use accelerated approval and which should stick to a more traditional approach. Generally, they said the speedier pathway is best suited for curative therapies targeting a monogenetic disease without available treatment options.
Another set of guidances will focus on several attractive therapeutic targets for gene therapies, including inherited blood disorders like hemophilia and certain neurodegenerative diseases. More documents about implementing manufacturing advances for CAR-T therapies will be put out as well, particularly with regard to how companies can make smaller tweaks without requiring costly clinical investigations.
Finally, on enforcement measures, the FDA is concerned about companies working outside of regulatory compliance, some of which have ignored agency requests to discuss how to comply. Gottlieb and Marks warned more disciplinary actions in 2019 for those that remain rogue.
While the FDA leaders touted the future of these therapies as promising in tackling some of the most difficult diseases, they also hedged their enthusiasm with caution.
"But with their novelty, also comes new uncertainties and some unique, theoretical risks," they wrote. "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."
Correction: This article has been updated to reflect the correct name of Gilead's cell therapy, Yescarta.