REGENXBIO Inc. has received a setback in its efforts to bring a gene therapy to patients with Hunter syndrome, after the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) declining approval of its Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec).
The therapy is designed to treat mucopolysaccharidosis II (MPS II), an ultra-rare inherited neurodegenerative disorder that primarily affects boys and leads to progressive cognitive decline, organ damage, and premature death. The FDA had accepted the application under the accelerated approval pathway in May 2025, but in a February 7, 2026 decision the agency concluded the evidence was insufficient to support approval.
According to the FDA, key uncertainties remain about the clinical development program. Regulators questioned whether the trial eligibility criteria adequately identified patients with neuronopathic disease rather than milder forms, whether the external natural-history comparison group was appropriate, and whether the biomarker used — CSF HS D2S6 — could reliably predict clinical benefit. The agency also outlined possible paths forward, including conducting a new study, enrolling additional patients with longer follow-up, or adding an untreated control arm, options that are difficult in ultra-rare disease populations.
REGENXBIO said it had attempted to address these issues during the review through additional data submissions and expert analyses, but the FDA ultimately determined the data did not demonstrate substantial evidence of effectiveness.
Company CEO Curran Simpson called the decision “devastating” for families and emphasized the company’s continued commitment to the program, which has been in development for more than a decade. The company plans to request a Type A meeting with the FDA to clarify next steps and aims to resubmit the application with further long-term clinical data and refined patient population definitions.
Clinical experts and patient advocates expressed disappointment. Joseph Muenzer, a leading MPS researcher at the University of North Carolina, said Hunter syndrome often causes irreversible brain damage and death in the mid-teens without effective intervention, adding that gene therapy could significantly alter outcomes. The National MPS Society also urged regulators to work quickly toward a viable path forward, noting families have waited decades for new treatment options.
REGENXBIO maintains confidence in RGX-121’s long-term potential and intends to pursue approval as rapidly as possible despite the regulatory hurdle.