Regenxbio received a complete response letter (CRL) from the U.S. Food and Drug Administration for RGX‑121, its gene therapy for Hunter syndrome (MPS II), and the agency has placed related programs on clinical hold. The FDA said it remained unconvinced by the surrogate endpoints and the use of historical controls, and flagged unresolved issues in trial comparisons and biomarker interpretation. Regenxbio said it will request a meeting to chart a path forward but warned options — fresh randomized trials or longer follow‑up — are difficult in ultra‑rare populations. The decision followed a related clinical hold after a treated participant in a separate Regenxbio program developed a brain tumor; regulators cited shared risks between the studies. The CRL highlights renewed FDA scrutiny on gene therapy evidence packages, especially reliance on biomarkers and non‑concurrent controls. Company management described the outcome as disappointing given the urgent unmet need; analysts expect extended delays to any potential approval timetable.