The Food and Drug Administration (FDA) rejected multiple gene and cell therapy treatments, including tabelecleucel (Ebvallo) for Epstein-Barr virus-positive post-transplant lymphoproliferative disease. The agency also rejected Regenxbio's gene therapy RGX-121 for mucopolysaccharidosis II, also known as Hunter syndrome.

Additionally, the FDA closed the accelerated approval pathway for uniQure's AMT-130, a treatment for Huntington's disease, and recommended a sham surgery-controlled study for it. Replimune's drug candidate for advanced melanoma was also rejected by the agency.

Atara Biotherapeutics and its partner Pierre Fabre Pharmaceuticals received a complete response letter from the FDA regarding tabelecleucel. Atara Biotherapeutics, Pierre Fabre Pharmaceuticals, Regenxbio, uniQure, and Replimune have all been given the opportunity to resubmit their applications.

Stephen Majors, vice president of global communications at the Alliance for Regenerative Medicine, commented on these developments. "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, "The fact that we're on a much more seemingly predictable and consistent path in terms of regulation is a big step forward."

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 also noted that 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 consistently demonstrated a "fixation on due process." According to Grossman, "What's needed now is a process that gives them a fair review."

The proportion of FDA complete response letters for cell and gene therapy approvals was 18% between 2020 and 2024. This proportion increased to 38% for the 2025-2026 period. Vinay Prasad left the FDA in March, and Marty Makary resigned from the FDA in May.

Why It Matters

The rejections of multiple gene and cell therapy treatments, coupled with the FDA's recommendation for a sham surgery-controlled study for AMT-130, indicate an evolving standard for regulatory approval in advanced therapies. The increased proportion of complete response letters for cell and gene therapy approvals from 18% in 2020-2024 to 38% in 2025-2026 suggests a more rigorous review process for these complex treatments. This shift affects pharmaceutical companies developing such therapies, as evidenced by the need for multiple companies to resubmit their applications.