RARE Daily

Regenxbio Reports Positive Results in Pivotal Trial of MPS II Study

February 8, 2024

Rare Daily Staff

Regenxbio reported the phase 1/2/3 CAMPSIITE trial of its one-time gene therapy RGX-121 for the treatment of patients up to 5 years old diagnosed with the lysosomal storage disorder mucopolysaccharidosis type II met its primary endpoint with statistical significance.

“The data from this pivotal trial supports that RGX-121 changes the course of disease by restoring the gene missing in boys with Hunter syndrome and has the potential to significantly improve vital brain function for patients living with this debilitating disease,” said Kenneth Mills, president and CEO of Regenxbio, who added the company expects to file an application for approval of the gene therapy with the U.S. Food and Drug Administration this year. “We have shared CAMPSIITE results with FDA leadership, and they have confirmed that, based on the totality of the evidence, they are open to accelerated approval if supported by review of the full data.”

MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues that ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. There is currently no treatment to address fatal neuronopathic CNS disease in MPS II.

RGX-121 is an investigational, one-time gene therapy designed to deliver the iduronate-2-sulfatase gene (IDS) that encodes the iduronate-2-sulfatase enzyme (I2S) using the NAV AAV9 vector. RGX-121 expressed protein is structurally identical to normal I2S. RGX-121 is administered directly to the central nervous system (CNS) using intracisternal or intracerebroventricular delivery. Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS.

RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.

“A one-time gene therapy that can help these boys develop beyond the natural history of the disease and may allow them to discontinue enzyme replacement therapy or remain ERT-naïve represents a meaningful breakthrough,” said Paul Harmatz, a physician with UCSF Benioff Children’s Hospital and trial investigator who presented the data at the 20th Annual WORLDSymposium.

In the pivotal phase, MPS II patients treated with RGX-121 achieved decreased cerebrospinal fluid (CSF) levels of D2S6, a key biomarker of brain disease activity, below maximum attenuated disease levels at 16 weeks. Patients receiving RGX-121 demonstrated an 86 percent median reduction in D2S6, approaching normal levels.

Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE. In the dose-finding phase, the majority of patients are exceeding expectations in neurodevelopmental function compared to natural history data up to four years. New long-term follow-up of patients treated with RGX-121 in the dose-finding phase also showed there was a high rate of patients for whom trial investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy (ERT) or were allowed to remain ERT-naïve. At the pivotal dose level, 80 percent of patients were ERT-free at last time point.

As of January 3, 2024, RGX-121 continues to be well tolerated in 25 patients dosed across all phases of the CAMPSIITE trial.

Regenexbio expects to file an application for approval of the gene therapy in the second half of 2024. Based on an expected priority review, potential approval of the planned application could result in receipt of a Rare Pediatric Disease Priority Review Voucher in 2025.

Photo: Kenneth Mills, president and CEO of Regenxbio

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