The U.S. Food and Drug Administration (FDA) is considering new regulatory requirements that could make it more challenging for companies developing CAR T-cell therapies to gain approval for their products.
In a Perspective article published in the Journal of the American Medical Association, Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, along with three co-authors from the agency, emphasized that while the FDA is willing to “exercise regulatory flexibilities, when necessary,” it must also “maintain the high evidentiary standards for approval.”
Prasad stated that randomized controlled trials will become the FDA’s “preferred approach” for evaluating CAR T products. According to reporting from FirstWord Pharma, this means regulators will focus on outcomes such as patient survival or time to disease progression.
Additionally, Prasad wrote that companies should compare their experimental CAR T therapies against existing standard treatments, including other approved CAR T products. He noted that single-arm trials without control groups—used in all seven currently approved CAR T therapies—will no longer be sufficient to support future approvals.
However, Prasad acknowledged that findings showing durable treatment responses from one-arm studies can still be used for accelerated approvals. For full approval, sponsors must establish clinical benefit through randomized and controlled trials.
These potential changes come at a time when the cell therapy sector has faced setbacks. Regeneron discontinued its early-stage bbT369 asset in October 2024 after acquiring it earlier in the year from 2seventybio; this decision was described as a “strategic business decision.” The drug was being studied in relapsed or refractory B-cell non-Hodgkin’s lymphoma. In March 2025, Cargo Therapeutics laid off most of its staff and halted development after its lead candidate failed a Phase II trial.
Gilead and Arcellx are among those who may be affected by these proposed guidelines. Their anti-BCMA therapy anitocabtagene autoleucel (anito-cel) is being evaluated in a registrational Phase II iMMagine-1 study without a control arm. At this year’s American Society of Hematology conference, Gilead and Arcellx reported an overall response rate of 96% for anito-cel and a complete/strict complete response rate of 74%. BMO Capital Markets commented on Sunday that these results could provide "a clear path to a potential 2026 approval/launch." It remains uncertain how any new FDA rules might impact anito-cel's regulatory process.
