The FDA issued a complete response letter rejecting Regenxbio’s RGX‑121 gene therapy for Hunter syndrome, citing concerns about patient population definition, reliance on a natural history control arm, and use of a biomarker (heparan sulfate) as a surrogate endpoint. Regenxbio said it will submit longer‑term data and is concerned about the agency’s feedback given the urgent unmet need for the ultra‑rare disease. Regulatory scrutiny follows a clinical hold earlier in the program after a brain tumor was found in a patient treated with a different Regenxbio gene therapy. The FDA’s Center for Biologics Evaluation and Research has increasingly questioned biomarker‑only accelerated approvals under its current leadership, signaling heightened evidentiary expectations for one‑time gene therapies.