Assessment of United States Food and Drug Administration Approval of Cell and Gene Therapies.

The development and use of cell and gene therapies (CGTs) are rapidly expanding and challenge traditional regulatory paradigms. With growing clinical use and high costs, rigorous evaluation of regulatory oversight by the US Food and Drug Administration (FDA) is increasingly important. We characterized premarketing evidence and postmarketing requirements and commitments for all 38 CGTs approved by the FDA through December 31, 2025. Most therapies used special designations and expedited pathways (86.8% had an orphan designation; 92.1% used an expedited pathway). The mean number of pivotal studies required for CGT approval was 1.6 (SD 1.7), with 73.7% approved based on a single study, and 44.7% relying solely on studies with surrogate endpoints. Reliance on postmarketing evidence generation was common, with 73.4% of products approved with at least one postmarketing requirement or commitment, totaling 52 studies. However, only 17.9% of CGTs had a postmarketing study that included a primary clinical efficacy endpoint, and most studies remain ongoing. These findings suggest that current regulatory approaches prioritize timely access but often rely on limited premarket data and postmarketing studies that infrequently assess clinical efficacy outcomes. Ensuring that requirements for preapproval trials and postmarketing studies are adequate and appropriately calibrated to the level of uncertainty and benefit-risk profile of individual CGTs may better support the goal of providing patients with timely, innovative, and transformative treatments that have the greatest potential to advance disease treatment.