FDA Rejects Application for Gene Therapy for Hunter Syndrome
The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec; REGENXBIO, Rockville, MD), meaning that, at this time, the FDA will not approve the investigational gene therapy for mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. The application had been submitted under the accelerated approval pathway for this ultra-rare, neurodegenerative pediatric disorder.
According to an announcement from REGENXBIO, in the CRL, dated February 7, 2026, the FDA did not agree that the submitted data provided substantial evidence of effectiveness to support approval. The FDA cited several areas of uncertainty, including challenges in defining a study population with neuronopathic MPS II as distinct from attenuated disease, limitations in the comparability of the external natural history control, and questions regarding the suitability of cerebrospinal fluid heparan sulfate D2S6 (CSF HS D2S6) as a surrogate end point reasonably likely to predict clinical benefit.
In the press release from REGENXBIO, the company stated that the FDA outlined potential paths forward that could support a future resubmission, including conducting a new study, treating additional individuals with longer-term follow-up, and incorporating an untreated control arm. REGENXBIO noted that the feasibility of these approaches may be limited by the ultra-rare nature of MPS II. The company has also announced that it plans to request a Type A meeting with the FDA to discuss the CRL and a potential resubmission strategy.
“I remain encouraged by the clinical data behind RGX-121,” said Joseph Muenzer, MD, PhD, Director of the Muenzer MPS Research and Treatment Center and Bryson Distinguished Professor in the Division of Genetics and Metabolism of the Department of Pediatrics Genetics at the University of North Carolina at Chapel Hill. “New innovations like gene therapy could make a significant impact for these patients, and time is precious for these families.”
RGX-121 is a 1-time, adeno-associated virus (AAV)–based gene therapy designed to deliver the iduronate-2-sulfatase (IDS) gene directly to the central nervous system to address the neurological manifestations of MPS II. The BLA was supported by biomarker, functional, and safety data from the CAMPSIITE I/II/III program, with follow-up reported through 12 months. RGX-121 has previously received Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations.
Source: REGENXBIO. REGENXBIO announces regulatory update on RGX-121 BLA for MPS II. REGENXBIO. Published February 9, 2026. Accessed February 10, 2026. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-regulatory-update-rgx-121-bla-mps-ii