FDA Clears Path for NAVSUNLI BLA Resubmission in MPS II, No Additional Studies Required

REGENXBIO announced it has reached alignment with the FDA on a path forward for the potential accelerated approval of NAVSUNLI (clemidsogene lanparvovec-sngl; RGX-121), a one-time investigational gene therapy for Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome.¹ The announcement marks a significant reversal from the complete response letter (CRL) the company received in February 2026, in which the agency had cited multiple evidentiary concerns and suggested additional studies before approval could be considered.

In a recent collaborative discussion conducted as part of REGENXBIO's appeal of the February CRL, the FDA confirmed that existing NAVSUNLI clinical data are sufficient for the accelerated approval pathway and that no additional patient enrollment or new studies are required, including the untreated concurrent control arm previously recommended.¹ The FDA asked REGENXBIO to request a Type A meeting to review existing longer-term biomarker and clinical data, with a BLA resubmission to follow on an expedited review basis. REGENXBIO expects the Type A meeting in July 2026 and the BLA resubmission in Q3 2026.

"We are encouraged by recent signals from the new FDA leadership reinforcing a commitment to address the unique nature of rare diseases and use the accelerated approval pathway to bring transformative therapies to patients with serious, unmet medical needs," Curran Simpson, President and CEO of REGENXBIO, said in a statement.¹

The February CRL had cited concerns about the ability of eligibility criteria to distinguish adequately between neuronopathic and attenuated forms of MPS II, the comparability of the external natural history control population, and the evidentiary strength of the CSF heparan sulfate (HS) D2S6 surrogate endpoint.² REGENXBIO had maintained that those concerns were already addressed during the BLA review period and flagged the difficulty of the previously suggested pathways given the ultra-rare nature of the disease, which affects approximately 2,000 patients worldwide.¹

The CAMPSIITE pivotal trial (NCT03566043) demonstrated an 85% median reduction in CSF HS D2S6 levels, with reductions approaching normal range and sustained through up to two years of follow-up.³ At the pivotal dose level, 80% of patients remained free of intravenous enzyme replacement therapy (ERT) beyond 18 months post-dosing.³ The primary endpoint of change in CSF D2S6 levels over 16 weeks was met with statistical significance when the pivotal data were first reported in early 2024.³

The January 2026 clinical hold on the CAMPSIITE program had added a further complication. That hold was triggered by a CNS tumor identified in a patient enrolled in RGX-111, a separate REGENXBIO AAV-based gene therapy for MPS I. The FDA placed both programs on hold due to shared product similarities, despite REGENXBIO's objection that the programs are distinct. Preliminary analysis indicated an AAV vector genome integration event associated with overexpression of PLAG1, a protooncogene. The current announcement implies that barrier has been sufficiently addressed to allow the review process to proceed.²

MPS II is a rare, X-linked recessive lysosomal storage disorder caused by iduronate-2-sulfatase (I2S) deficiency, leading to glycosaminoglycan accumulation in the CNS and other tissues. Most patients have the severe neuronopathic form, with developmental delay apparent by 18 to 24 months and premature death typically in the mid-teens. Current standard of care relies on weekly intravenous ERT with idursulfase, which does not cross the blood-brain barrier. NAVSUNLI is designed to deliver the IDS gene to the CNS via AAV9, providing a permanent source of I2S beyond that barrier. If approved, it would be the first gene therapy and the first one-time treatment for MPS II.

Approval under the accelerated pathway would require confirmatory evidence of clinical benefit post-approval. Under a partnership announced in January 2025, NS Pharma holds U.S. commercialization rights following potential approval, and REGENXBIO could receive a Priority Review Voucher.¹

REFERENCES
1. REGENXBIO announces alignment with FDA on path forward for NAVSUNLI BLA resubmission for accelerated approval; first potential gene therapy for MPS II. News release. REGENXBIO Inc. June 22, 2026. Accessed June 24, 2026. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-announces-alignment-fda-path-forward-navsunli-bla
2. REGENXBIO announces regulatory update on RGX-121 BLA for MPS II. News release. REGENXBIO Inc. February 9, 2026. Accessed June 24, 2026. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-twelve-month-pivotal-data-phase
3. REGENXBIO announces positive data from pivotal dose level of RGX-121 demonstrating long-term systemic effect. News release. REGENXBIO Inc. September 3, 2024. Accessed June 24, 2026. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-positive-data-pivotal-dose-level-rgx-121