The United States Food and Drug Administration (FDA) issued multiple rejections for cell and gene therapy applications in early 2025. In January, the FDA sent a complete response letter to Atara Biotherapeutics and Pierre Fabre Pharmaceuticals, rejecting the T-cell immunotherapy tabelecleucel for Epstein-Barr virus-positive post-transplant lymphoproliferative disease. The agency subsequently rejected Regenxbio's gene therapy RGX-121 for mucopolysaccharidosis II in February and declined accelerated approval for uniQure's AMT-130 treatment for Huntington's disease in March.

The FDA also recommended a sham surgery-controlled study for uniQure's AMT-130 as part of its review process. In April, Replimune's drug candidate for treating advanced melanoma was rejected by the agency. Atara Biotherapeutics, Pierre Fabre Pharmaceuticals, Regenxbio, uniQure, and Replimune have all received opportunities to resubmit their drug applications.

Stephen Majors, vice president of global communications at the Alliance for Regenerative Medicine, commented on the regulatory environment. "I view these reversals as a turning of the page from a less predictable chapter in which agency leaders seemed to surprise sponsors with new ideas on what constitutes sufficient evidence," Majors said. He added that the current path appears "much more seemingly predictable and consistent in terms of regulation." Majors also stated, "The shift away from requiring a bunch of randomized controlled trials for rare disease drugs, given the fast-moving nature of these illnesses, is a positive signal."

Robert Steinbrook, director of the Health Research Group at Public Citizen, offered a different perspective. He indicated that the situation suggests "chaos and confusion than a clear pattern, one way or the other, about the FDA standards for reviewing drugs and biologics." Steinbrook also addressed company announcements, saying, "Companies have a vested interest in telling investors that the FDA views drug candidates favorably, but until the FDA actually reaches a decision, that's just company spin."

Robert Califf, a former FDA commissioner and adjunct professor at Duke University School of Medicine, stated, "FDA leadership under the Trump administration, since day one, has been politically overriding staff, which almost never happened before." Califf noted an instance where "Tracy Beth Høeg left no written record of her counter-perspective, despite reported disagreements with staff over the drug's approval." He added that current conditions "do seem to be more settled down, but tha..." and that "the agency's stability going forward hin..." The proportion of FDA complete response letters for cell and gene therapy approvals increased from 18% of decisions between 2020 and 2024 to 38% between 2025 and 2026.

Why It Matters

The FDA's recent rejections of multiple cell and gene therapy applications in early 2025 impact several pharmaceutical and biotechnology companies and their drug development timelines. The requirement of a sham surgery-controlled study for one treatment suggests a rigorous evidentiary standard being applied to novel therapies. The discussion among experts reflects differing views on the agency's current regulatory consistency, with some indicating improved predictability and others pointing to potential instability that could influence future drug approvals.