The Food and Drug Administration issued a complete response and rejected Regenxbio’s accelerated approval application for RGX-121, a one-time gene therapy for the severe form of Hunter syndrome. The agency raised concerns about patient population definition, use of a natural history control arm, and reliance on heparan sulfate biomarker data as a surrogate for cognitive outcomes. Regenxbio said it will pursue resubmission with longer-term data. The decision highlights growing FDA scrutiny of biomarker-driven approvals and the regulatory hurdles that rare-disease developers face when relying on surrogate endpoints or non-randomized comparators. Company leadership expressed dismay and signaled plans to engage regulators to clarify a path forward.