REGENXBIO Announces That FDA Issued Complete Response Letter For RGX-121 For Treatment Of Mucopolysaccharidosis II; Co. Plans To Work With FDA On A Path Forward With The Goal Of Resubmitting The BLA

REGENXBIO Inc. (NASDAQ:RGNX) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec) for the treatment of Mucopolysaccharidosis II (MPS II), an ultra-rare neurodegenerative disease also known as Hunter syndrome.

In May 2025, the FDA accepted the RGX-121 BLA under the accelerated approval pathway. In the February 7, 2026 CRL, the FDA stated that it had agreed to the study protocol in principle and outlined several reasons for not approving the gene therapy, including uncertainty regarding the study eligibility criteria to adequately define a population with neuronopathic disease (vs. attenuated disease), the comparability of the natural history external control to the study population, and the appropriateness of CSF HS D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. The CRL lists several potential paths forward, including a new study, treating additional patients and conducting longer-term follow up, and using an untreated control arm, all of which would be challenging in an ultra-rare disease population, like MPS II.

"This decision is devastating for the families of boys living with this progressive, life-threatening disease," said Curran Simpson, President and CEO of REGENXBIO. "We are concerned about FDA's feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease. We remain confident in the quality and volume of evidence demonstrating the long-term potential of RGX-121 to positively change the trajectory of Hunter syndrome. This program has been in development for over 10 years. We are incredibly grateful to all the patients, their families, investigators, and site staff who have supported this program and our continued efforts to bring a much-needed new treatment option to the Hunter syndrome community. We will continue those efforts."

Throughout active discussions during the BLA process, REGENXBIO believed it had addressed the points raised in the CRL through the submission of additional data and responses to numerous information requests. Independent, leading global MPS and biomarker experts conducted analyses and reviews with the FDA, as well. Ultimately, the FDA did not agree the data set provided substantial evidence of effectiveness to support approval of RGX-121 for the treatment of MPS II.

REGENXBIO plans to request a Type A meeting to discuss the CRL, as well as the planned BLA resubmission to provide additional evidence from global MPS II experts to further clarify the neuronopathic patient population and additional longer-term clinical data to support evidence of effectiveness. REGENXBIO intends to find a path forward as quickly as possible with the goal of resubmitting the BLA.

"MPS II is a very complex disease, but its impact is well established, resulting in irreversible brain damage for the majority of patients; without appropriate treatments stopping this neurocognitive decline, the neuronopathic MPS II child will die prematurely, usually in their mid-teens," said Joseph Muenzer, M.D., Ph.D., Director, Muenzer MPS Research and Treatment Center, Bryson Distinguished Professor in the Division of Genetics and Metabolism, Department of Pediatrics Genetics, University of North Carolina at Chapel Hill. "I remain encouraged by the clinical data behind RGX-121. New innovations like gene therapy could make a significant impact for these patients, and time is precious for these families."

"I've seen the severe impact of MPS II on patients and their families firsthand and am extremely disheartened by today's news," said Terri Klein, President and CEO, National MPS Society. "Families know the devastating trajectory of this disease all too well and have waited 20 years for new treatment options. They cannot wait any longer. Drug development for ultra-rare disease must be streamlined to allow new medicines to reach patients. We urge the FDA to find a swift path forward so that boys living with MPS II and their families have the chance for a better life."