The FDA issued a complete response rejecting Regenxbio’s RGX‑121 gene therapy for Hunter syndrome, citing concerns about patient‑population definition, use of a natural‑history control arm and reliance on a biomarker surrogate endpoint, Regenxbio said. The company had pursued accelerated approval based on reductions in cerebrospinal fluid heparan sulfate. Regenxbio stated it will resubmit with longer‑term data and expressed concern about the agency’s feedback given the urgent unmet need for this ultra‑rare, progressive pediatric disease. The decision follows a clinical hold tied to an unrelated patient’s later‑discovered brain tumor after receipt of a different Regenxbio gene therapy. Regulatory unease under CBER leadership about surrogate endpoints and trial controls has rippled across rare‑disease gene‑therapy approvals, and the decision will influence development strategies and dialogue around accelerated pathways for single‑dose central nervous system therapies.