Regenxbio Inc. (NASDAQ: RGNX) recently announced a regulatory update from the U.S. Food and Drug Administration (FDA) regarding its investigational gene therapy programs for the treatment of mucopolysaccharidosis (MPS) I and II, also known as Hurler and Hunter syndromes. The FDA placed a clinical hold on its investigational gene therapy, RGX-111, for the treatment of MPS I, following the preliminary analysis of a single case of neoplasm (intraventricular CNS tumor) in a participant treated in its phase I/II study.
Furthermore, the FDA also placed a clinical hold on RGX-121, for the treatment of MPS II, citing the similarities in products, study populations, and shared risk between the clinical studies.
This decision comes following the identification of a case during a routine brain MRI of an asymptomatic five-year-old participant who received intracisternal RGX-111 four years prior. The preliminary genetic analysis of the resected tumor detected an AAV vector genome integration event associated with overexpression of a proto-oncogene (PLAG1), which is known to be susceptible to chromosomal rearrangements.
Regenxbio's leadership expressed surprise at the FDA's decision, particularly regarding the hold on the RGX-121 program, emphasizing that the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged.
The company highlighted that patient safety is its top priority and expressed confidence in the benefit-risk ratio of RGX-121, noting the meaningful efficacy profile demonstrated in the pivotal trial.
It's important to note that no evidence of neoplasm has been reported in the nine other participants treated with RGX-111 nor in the 32 participants treated with RGX-121. The investigation to determine if this serious adverse event is drug-related is ongoing, and the causality has not been established. The participant continues to be asymptomatic, with positive developmental advancements noted by the treating physician.
Regenxbio has not yet received the full clinical hold letter and is awaiting additional details from the FDA. RGX-121 (Clemidsogene lanparvovec) is a potential one-time gene therapy for the treatment of boys with MPS II, designed to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system (CNS).
The company stated that RGX-121 has received orphan drug product, rare pediatric disease, fast track, and regenerative medicine advanced therapy (RMAT) designations from the FDA, and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.
MPS II, or Hunter syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme IDS, leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues, resulting in cell, tissue, and organ dysfunction, including in the CNS.
Regenxbio also provided information about RGX-111, which is designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene to the CNS. The delivery of the IDUA gene within the cells in the CNS could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS.
MPS I is a rare autosomal recessive genetic disease caused by a deficiency in the lysosomal enzyme alpha-l-iduronidase (IDUA), leading to an accumulation of GAGs in tissues, which ultimately results in cell, tissue, and organ dysfunction, including in the CNS.
Regenxbio Inc. is a biotechnology company focused on the curative potential of gene therapy. The company is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202 for the treatment of Duchenne muscular dystrophy, Navsunli for the treatment of MPS II, and RGX-111 for the treatment of MPS I, among others. As a result of these announcements, the company's shares have moved -1.02% on the market, and are now trading at a price of $13.62. For the full picture, make sure to review REGENXBIO's 8-K report.
