REGENXBIO Inc. said the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for its biologics license application (BLA) for RGX-121 (clemidsogene lanparvovec), a one-time gene therapy candidate for Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.
The CRL received on February 7, 2026 which means the FDA has declined to approve the application at this time, citing concerns around the clinical data package and its ability to demonstrate substantial evidence of effectiveness. Key issues noted include the definition of the neuronopathic patient population, use of external control data, and whether the surrogate biomarker used in the trial reliably predicts clinical benefit.
REGENXBIO previously secured FDA acceptance and priority review for the RGX-121 BLA in May 2025 under the accelerated approval pathway.
In response to the setback, REGENXBIO said it plans to work closely with the FDA to define a clear path forward, including requesting a formal meeting to discuss resubmission with additional clinical evidence. Management reaffirmed its commitment to advancing RGX-121, which has been in development for over a decade, and highlighted the urgent unmet need in the ultra-rare and life-threatening MPS II population.
The regulatory decision also coincides with broader challenges for REGENXBIO’s rare disease programs, including recent clinical holds on related gene therapy studies.
RGX-121 was designed as a potential one-time treatment intended to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system to address both neurological and systemic manifestations of Hunter syndrome.
