FDA Set to Require Randomized Trials and Superiority Data for Full CAR T Approval

WASHINGTON, D.C. — December 9, 2025—

The U.S. Food and Drug Administration (FDA) is signaling a significant tightening of its regulatory standards for CAR T-cell therapies, a change that could make it considerably harder for companies to secure full approval for their products.

In a “Perspective” piece published Monday in the Journal of the American Medical Association (JAMA), Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research (CBER), and three co-authors outlined the agency’s evolving expectations for this cutting-edge class of gene therapies.

The core message is a move away from the single-arm trials that supported the initial approval of all seven currently marketed CAR T therapies. Prasad wrote that assessing new CAR T products through randomized controlled trials (RCTs) will be the FDA’s “preferred approach” for traditional approval moving forward.

Superiority Over Standard of Care Required

For a traditional approval, new CAR T therapies will now generally be expected to establish superiority over current standard treatments, including CAR T products already on the market. The agency will focus on direct clinical endpoints, such as patient survival or time to a specific event.

While durable treatment response findings from single-arm studies may still be utilized for accelerated approvals, sponsors will be required to confirm clinical benefit through a rigorous randomized and controlled trial for full, traditional approval. The authors stressed that while the FDA aims to “exercise regulatory flexibilities,” it must also “maintain the high evidentiary standards for approval.”

Industry Impact Felt Immediately

The stricter guidelines cast a shadow over the already-strained cell therapy space, which has recently seen several high-profile exits.

The most notable program immediately affected by the proposed changes is Gilead and Arcellx’s anti-BCMA therapy, anitocabtagene autoleucel (anito-cel). The partners are currently running the registrational Phase II iMMagine-1 study, which notably does not include a control arm.

Despite recently touting a 96% overall response rate for anito-cel at the American Society of Hematology annual conference—findings BMO Capital Markets called a “clear path to a potential 2026 approval/launch”—it remains unclear how the new FDA guidance will affect the drug’s regulatory timeline and prospects for full approval.

The guidelines follow recent corporate setbacks in the sector, including Regeneron’s decision in October to discontinue its early-stage CAR T candidate, bbT369 (acquired from 2seventybio), and the closure of CAR T specialist Cargo Therapeutics in March after its lead asset failed a Phase II study.