U.S. — The U.S. Food and Drug Administration (FDA) rejected four cell and gene therapy treatments for rare diseases in early 2025. The agency has allowed the sponsoring companies to resubmit their applications in recent weeks.

In January, the FDA sent a complete response letter to Atara Biotherapeutics and Pierre Fabre Pharmaceuticals, rejecting the T-cell immunotherapy tabelecleucel (Ebvallo) for Epstein-Barr virus-positive post-transplant lymphoproliferative disease. In February, the FDA rejected Regenxbio's gene therapy RGX-121 for mucopolysaccharidosis II, also known as Hunter syndrome. In March, the agency declined accelerated approval for uniQure's AMT-130 treatment for Huntington's disease and recommended a sham surgery-controlled study. In April, the FDA rejected Replimune's drug candidate for treating advanced melanoma.

Stephen Majors, vice president of global communications at the Alliance for Regenerative Medicine, described the developments 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. "The fact that we're on a much more seemingly predictable and consistent path in terms of regulation is a big step forward," Majors said. He added that 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. "To me, this speaks more of chaos and confusion than a clear pattern, one way or the other, about the FDA standards for reviewing drugs and biologics," Steinbrook said. He stated that 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." Steinbrook also said, "The FDA cannot be a good regulatory authority without sufficient staff with scientific expertise."

Steven Grossman, a public policy and FDA regulatory consultant for HPS Group, said, "The FDA has always had a fixation on due process." He added, "They may turn you down in the end, but they want to make sure that everybody, including you, knows that they gave you every opportunity to be heard and to put your best foot forward." Grossman noted, "What's needed now is a process that gives them a fair review."

Why It Matters

The proportion of FDA complete response letters for cell and gene therapy approvals increased from 18% of decisions in 2020-2024 to 38% in 2025-2026.