REGENXBIO Inc. announced that the U.S. Food and Drug Administration has extended its review timeline for the Biologics License Application of clemidsogene lanparvovec (RGX-121) for treating Mucopolysaccharidosis II, commonly known as Hunter syndrome. The Prescription Drug User Fee Act goal date has been moved from November 9, 2025 to February 8, 2026.
The extension follows the company's submission of longer-term clinical data for all patients in the pivotal study of RGX-121 (n=13) in response to an FDA information request. These positive 12-month clinical data are consistent with biomarker and neurodevelopmental data previously submitted on the same patients in the BLA and will be presented during the International Congress of Inborn Errors of Metabolism in September 2025.
Regulatory Progress and Manufacturing Readiness
In August 2025, the FDA completed a pre-license inspection and bioresearch monitoring information inspection for the RGX-121 BLA with no observations. No safety-related concerns have been raised by the FDA during the BLA review process.
The regulatory pathway for RGX-121 has been supported by multiple FDA designations, including Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations. The therapy has also received advanced therapy medicinal products classification from the European Medicines Agency.
REGENXBIO previously completed a successful Pre-BLA meeting with the FDA in June 2024, where the agency confirmed alignment on using cerebrospinal fluid levels of heparan sulfate D2S6, a key biomarker of brain disease activity, as a surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval of RGX-121.
Clinical Development and Trial Results
The pivotal program utilized commercial-scale cGMP material from REGENXBIO's proprietary NAVXpress manufacturing process. Topline results from the Phase I/II/III CAMPSIITE trial demonstrated that the pivotal phase met its primary endpoint with statistical significance. Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE, in which the majority of patients were shown to be exceeding expectations in neurodevelopmental function compared to natural history data up to four years.
Long-term follow-up of patients treated with RGX-121 showed a high rate of patients for whom trial investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy or were allowed to remain ERT-naïve. As of January 3, 2024, RGX-121 continued to be well tolerated in 25 patients dosed across all phases of the CAMPSIITE trial.
Addressing Unmet Medical Need
"Boys with this rare, devastating disease have no treatment options to address neurodevelopmental decline, and the Hunter syndrome community is in urgent need for a therapeutic option with the potential to improve these patients' lives," said Curran M. Simpson, President and Chief Executive Officer of REGENXBIO. "We promptly provided the FDA with the information requested and expect the commercial launch plans remain on track."
MPS II is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase leading to an accumulation of glycosaminoglycans, including heparan sulfate in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system. The disease is estimated to occur in 1 in 100,000 to 170,000 births. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months.
Gene Therapy Mechanism
RGX-121 is designed as a potential one-time AAV therapeutic for the treatment of boys with MPS II, delivering the iduronate-2-sulfatase gene to the central nervous system. Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted iduronate-2-sulfatase protein beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. The RGX-121 expressed protein is structurally identical to normal I2S.
If approved, RGX-121 would be the first and only potential one-time commercially-available therapy designed to directly address the underlying genetic cause of Hunter syndrome. Based on an expected priority review, potential approval of the planned BLA could result in receipt of a Rare Pediatric Disease Priority Review Voucher in 2025.
