For traditional approval, CAR T therapies will need to establish superiority over current standard treatments, including already-approved CAR T products.
The FDA is eyeing regulatory changes that could make it harder for companies developing CAR T therapies to secure approvals for their products.
In a Perspective piece published Monday in the the Journal of the American Medical Association, Vinay Prasad, director of the agency’s Center for Biologics Evaluation and Research, along with three co-authors at the FDA, noted that while the FDA is adjusting its processes to “exercise regulatory flexibilities, when necessary,” it also needs to “maintain the high evidentiary standards for approval.”
In the future, Prasad wrote, assessing CAR T products though randomized controlled trials will be the FDA’s “preferred approach,” according to reporting from FirstWord Pharma, noting that the agency will be looking at the candidate’s effects on patient survival or on the time to the development of a particular event.
In addition, companies should also test their experimental CAR T therapies against existing standard treatments, including other CAR T products on the market, Prasad wrote in the JAMA piece. Single-arm trials with no controls will no longer be enough to support a CAR T approval. All seven CAR T therapies on the market were approved based on such studies.
Still, Prasad noted that durable treatment response findings from these one-arm studies can be used for accelerated approvals, but sponsors will still need to establish clinical benefit in a randomized and controlled trial for full approval.
These new CAR T guidelines add to the already-burdened cell therapy space, which in recent months has seen several high-profile exits and discontinuations. In CAR T, specifically, Regeneron in October canned the early-stage bbT369, which it obtained in January 2024 from 2seventybio, in what a spokesperson said was a “strategic business decision.” The asset was being tested in relapsed or refractory B-cell non-Hodgkin’s lymphoma. In March, CAR T specialist Cargo Therapeutics fired 90% of its staff and stopped all development work after its lead asset failed a Phase II study in January.
Two players that Prasad’s new CAR T guidelines could affect are Gilead and Arcellx, which are working together on the anti-BCMA therapy anitocabtagene autoleucel (anito-cel). The partners are running the registrational Phase II iMMagine-1 study, which does not include a control arm.
At this year’s annual conference of the American Society of Hematology, Gilead and Arcellx touted a 96% overall response rate for anito-cel, including a 74% complete response/stringent complete response rate. BMO Capital Markets on Sunday said these findings open a “clear path to a potential 2026 approval/launch.” It remains unclear how the FDA’s new CAR T rules will affect anito-cel’s regulatory timeline and prospects.
