FDA Delays Decision on Regenxbio's Hunter Syndrome Gene Therapy

The U.S. Food and Drug Administration (FDA) has extended its review period for Regenxbio's Hunter syndrome gene therapy, clemidsogene lanparvovec (RGX-121), pushing the target action date from November 9, 2025, to February 8, 2026. This three-month delay comes as the agency reviews additional longer-term clinical data submitted by the company.

Extended Review Period and Additional Data

Regenxbio filed the supplementary information after the FDA requested more data during the review process. The company provided 12-month data from the 13 patients included in RGX-121's pivotal trial, which Regenxbio reports are consistent with previously submitted biomarker and neurodevelopmental data on the same patients.

Despite the delay, Regenxbio remains optimistic about the therapy's prospects. CEO Curran Simpson stated that the company is "on track" with launch preparations for clemidsogene lanparvovec. The FDA has completed pre-license and bioresearch monitoring information inspections for RGX-121 with no objections, and no safety concerns have been raised about the Hunter syndrome candidate.

Hunter Syndrome and RGX-121

Hunter syndrome, also known as mucopolysaccharidosis type II, is a rare, X-linked genetic disease caused by mutations in the IDS gene. This leads to a buildup of glycosaminoglycans and heparan sulfate in various tissues, resulting in organ damage and, in severe cases, developmental delays apparent by age two.

RGX-121 is designed as a one-time gene therapy to deliver a functional copy of the IDS gene to the central nervous system. This approach aims to address the neurological symptoms of Hunter syndrome, which current enzyme replacement therapies cannot effectively treat due to their inability to cross the blood-brain barrier.

The therapy has received orphan drug product, rare pediatric disease, and regenerative medicine advanced therapy designations from the FDA. In February 2024, Regenxbio reported an 86% reduction in a key disease biomarker in the cerebrospinal fluid of patients 16 weeks after treatment in a Phase I/II/III study.

Regulatory Challenges in Gene Therapy

The delay for RGX-121 adds to a growing list of regulatory challenges faced by gene therapies. In July 2025, the FDA rejected Ultragenyx's UX111 for Sanfilippo syndrome type A due to manufacturing issues. In May of the same year, Rocket Therapeutics' RP-A501 for Danon disease was placed on clinical hold following a patient death.

These setbacks highlight the complex regulatory landscape for gene therapies, particularly for ultra-rare diseases. Dr. Joseph Muenzer, a pediatrician and Hunter syndrome expert at the University of North Carolina, noted the difficulties in conducting large-scale, randomized, placebo-controlled trials for such rare conditions. He emphasized the ethical concerns of potentially subjecting patients to irreversible brain damage in placebo groups.

As the pharmaceutical industry continues to navigate these challenges, the outcome of Regenxbio's extended review period will be closely watched by stakeholders in the gene therapy field.