The FDA issued a complete response letter rejecting Regenxbio’s RGX‑121 for Hunter syndrome, citing concerns about surrogate endpoints, historical controls, and the robustness of the evidence package. Regenxbio said the agency agreed "in principle" with the trial design but found multiple unresolved issues and outlined potential paths including new trials or longer follow‑up. The decision follows a prior clinical hold and safety review after an unrelated trial participant developed a brain tumor, prompting FDA caution on related AAV programs. Regenxbio plans to request a meeting to discuss resubmission options; the regulator’s stance signals intensified scrutiny of gene‑therapy evidence and control strategies in ultra‑rare disorders.