The FDA issued a complete response letter rejecting Regenxbio’s Biologics License Application for RGX‑121, citing inadequate controls, heterogeneous patient sampling, and insufficient evidence that the chosen cerebrospinal fluid surrogate predicts clinical benefit. The regulator told Regenxbio to show normalization of a relevant biomarker or neurodevelopmental improvement or to conduct a new late‑stage study with appropriate untreated controls. The agency acknowledged earlier engagement but concluded the totality of uncertainties prevents approval. Regenxbio now faces program redesign options: run a new controlled trial, enroll additional patients under a modified protocol, or seek alternative endpoints—choices that will influence timelines, cost and the precedent for other rare‑disease gene therapies.