Surabgene Lomparvovec

Rockville, Maryland-based Regenxbio Inc. (Nasdaq: RGNX) has announced alignment with the US FDA on a path forward for resubmission of the Biologics License Application (BLA) for Navsunli (clemidsogene lanparvovec-sngl, RGX-121), an adeno-associated virus gene therapy for Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome. The development is significant because it revives what would be the first potential gene therapy for an ultra-rare, progressive neurodegenerative disease affecting approximately 2,000 patients worldwide, and it comes after a protracted regulatory sequence that included a Complete Response Letter, a clinical hold, and an appeal. The FDA’s willingness to review the application without requiring additional studies suggests the agency’s concerns were focused on evidentiary interpretation rather than a fundamental deficiency in the clinical dataset. The filing seeks accelerated approval via the BLA resubmission pathway, targeting boys with neuronopathic MPS II. The FDA confirmed that no additional clinical studies are required and that existing longer-term biomarker and clinical data from the CAMPSIITE study will be reviewed on an expedited basis. Regenxbio said it expects a Type A meeting with the FDA in July 2026, followed by a BLA resubmission in Q3 2026. The company did not disclose a projected PDUFA target action date at this stage, but the FDA indicated labeling discussions would commence shortly following resubmission. If approved, Navsunli would represent the first one-time, potentially curative treatment for MPS II and could trigger a Rare Pediatric Disease Priority Review Voucher, the proceeds from which Regenxbio retains in full. The regulatory path to this point has been notably turbulent. The FDA accepted the original BLA for priority review in May 2025 with a PDUFA date of November 9, 2025, which was subsequently extended to February 8, 2026 after Regenxbio submitted longer-term clinical data in response to an FDA information request. In February 2026, the FDA issued a Complete Response Letter, citing concerns about study eligibility criteria, the comparability of the natural history external control, and the appropriateness of cerebrospinal fluid (CSF) heparan sulfate D2S6 as a surrogate endpoint. Separately, in January 2026, the FDA placed a clinical hold on both Navsunli and Regenxbio’s MPS I program RGX-111 following a neoplasm case in a patient treated with RGX-111. That hold on Navsunli was subsequently lifted, as confirmed in Regenxbio’s Q1 2026 earnings update. The current announcement reflects the outcome of Regenxbio’s appeal of the CRL, during which the FDA acknowledged the existing data are sufficient for consideration under the accelerated approval pathway. The clinical evidence underpinning the resubmission draws on the CAMPSIITE Phase I/II/III trial, a multicenter, open-label study enrolling boys with neuronopathic MPS II aged four months up to five years. The pivotal phase of the trial met its primary endpoint with statistical significance, demonstrating an 86% median reduction in CSF D2S6 — a key biomarker of brain disease activity — approaching normal levels at 16 weeks (p\=0.00016). Long-term follow-up data from the dose-finding phase showed the majority of patients exceeding expectations in neurodevelopmental function compared to natural history data up to four years, and a high proportion of investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy or allowed patients to remain ERT-naïve. The BLA resubmission will incorporate this existing longer-term biomarker and clinical dataset rather than requiring enrollment of additional patients or a new untreated control arm, the FDA confirmed. Navsunli uses an AAV9 vector to deliver the iduronate-2-sulfatase (IDS) gene directly to the central nervous system via intracisternal or intracerebroventricular administration, designed to provide a permanent source of secreted I2S protein beyond the blood-brain barrier. The expressed protein is structurally identical to normal I2S. This mechanism is distinct from the approach taken by the only recently approved neurologic MPS II therapy: Denali Therapeutics’ Avlayah (tividenofusp alfa-eknm), an enzyme replacement therapy fused to a transferrin receptor-targeting TransportVehicle platform, which received accelerated FDA approval in March 2026 for the treatment of neurologic manifestations of Hunter syndrome in pediatric patients. Of note, Avlayah requires weekly intravenous infusions; Navsunli, if approved, would offer a one-time administration, a distinction that carries meaningful clinical and practical implications for families managing a progressive disease with a median life expectancy in the mid-teens for severe neuronopathic forms. The competitive and scientific context for a gene therapy in MPS II is materially different now than when the original BLA was filed. Avlayah’s approval established that CSF heparan sulfate reduction is an acceptable surrogate endpoint for accelerated approval in neurologic MPS II, providing a degree of regulatory precedent that may support the evidentiary framework for Navsunli’s resubmission. The broader MPS gene therapy field is also advancing: Ultragenyx Pharmaceutical’s UX111 (rebisufligene etisparvovec), an AAV9 gene therapy for the related condition MPS IIIA (Sanfilippo syndrome Type A), had its BLA resubmission accepted by the FDA in April 2026 with a PDUFA date of September 19, 2026 — a parallel regulatory trajectory that underscores the FDA’s current engagement with gene therapies for lysosomal storage diseases affecting the CNS. For Regenxbio, the Navsunli program sits alongside two other late-stage assets: RGX-202 for Duchenne muscular dystrophy, which reported positive topline pivotal Phase III data in May 2026 and is being prepared for a BLA submission seeking accelerated approval, and surabgene lomparvovec (ABBV-RGX-314) for wet AMD and diabetic retinopathy, developed in collaboration with AbbVie, with pivotal data expected in Q4 2026. Commercialization of Navsunli following potential approval would be led by NS Pharma, a subsidiary of Nippon Shinyaku, under a strategic partnership announced in January 2025. Regenxbio retains responsibility for clinical and commercial manufacturing at its in-house facility in Rockville. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.