Delays from the FDA continue to pile up, with Maryland-based Regenxbio the latest to report the review of one of its assets has been extended.
The Prescription Drug User Fee Act (PDUFA) date for Regenxbio’s Hunter syndrome gene therapy clemidsogene lanparvovec (RGX-121) has been pushed from Nov. 9 to Feb. 8, 2026, the company announced in an Aug. 18 release.
The FDA had accepted Regenxbio’s application for accelerated approval on May 13, the biotech said in a prior announcement.
At some point during the review, the FDA requested further data from Regenxbio, according to the new release. The company responded with 12-month data from the 13 patients included in RGX-121’s pivotal trial, which “are consistent with biomarker and neurodevelopmental data previously submitted on the same patients,” Regenxbio said.
This month, the FDA completed its pre-license and bioresearch monitoring information inspections for RGX-121 with no objections, Regenxbio said, and the agency has also raised no safety concerns about the Hunter syndrome candidate.
RGX-121 is a one-time gene therapy meant to deliver a functional copy of the iduronate-2-sulfatase (IDS) gene to the central nervous system. Boys with Hunter syndrome lack the enzyme this gene makes, which is needed to break down certain sugars. Without IDS, sugars build up inside cells, causing many complications including heart disease, breathing problems and loss of brain function.
"Boys with this rare, devastating disease have no treatment options to address neurodevelopmental decline, and the Hunter syndrome community is in urgent need for a therapeutic option with the potential to improve these patients' lives," Curran Simpson, president and CEO of Regenxbio, said in the release.
Regenxbio’s stock took a dip after announcing the delay, dropping 7% from $8.70 per share at yesterday’s close to $8.10 at 10:20 a.m. ET today.
"FDA performs thorough reviews of applications to ensure sound decisions. Timelines can be affected by the complexity of an application and submission of new data during the review of the file, among other factors," a spokesperson for the Department of Health and Human Services, which oversees the FDA, told Fierce Biotech on Aug. 19. "FDA is on track to meet the new PDUFA goal date."
While enzyme replacement therapies can treat the disease, they aren't able to cross the blood-brain barrier to stop neurological symptoms, Joseph Muenzer, M.D., Ph.D., a pediatrician and expert in Hunter syndrome and related diseases at the University of North Carolina, told Fierce.
“We have a treatment for the physical disease to some extent, but we don't have a treatment for the brain disease,” Muenzer said.
The FDA’s delay and request for more data bears the fingerprints of Vinay Prasad, M.D., the head of the agency’s Center for Biologics Evaluation and Research, Muenzer said. The recently returned Prasad has expressed disdain for accelerated approvals based on biomarkers like the kind Regenxbio is pursuing, preferring randomized, placebo-controlled trials with clinical outcomes data instead.
But such a trial would be nearly impossible—and unethical—to run in Hunter syndrome, Muenzer said.
For ultrarare diseases, “you can't enroll hundreds of patients, they just don't exist,” Muenzer explained. Even if you could enroll enough patients, showing a difference between treatment and placebo would take years due to how Hunter symptoms develop, and “that placebo group suffers irreversible brain damage,” Muenzer added. “You're basically sacrificing a generation of patients.”
Heparan sulfate levels, which Regenxbio and others developing Hunter treatments use as a biomarker in place of clinical outcomes, are widely accepted by the research community as an endpoint for accelerated approval.
Despite the delay, Regenxbio expects the commercial launch of RGX-121 to proceed as planned, Simpson said in the release. The biotech teamed up with Japan’s Nippon Shinyaku in January to commercialize RGX-121 in the U.S. and Asia, alongside another gene therapy for Hurler syndrome, RGX-111.
News of Regenxbio’s delay comes just days after another biotech, Neurizon, announced the FDA had pushed back the timeline for a decision about a clinical hold on its investigational amyotrophic lateral sclerosis (ALS) asset. Neurizon’s was the second ALS asset to be delayed by the agency, after Coya Therapeutics was dealt a similar hand for its investigational new drug application at the end of July.
While FDA Commissioner Marty Makary, M.D., pledged in June that the agency was on track to meet all of its PDUFA deadlines, the reality before and since has not aligned with his statements. Amid deep staffing cuts, the regulator has delayed or missed PDUFA dates for Stealth Therapeutics’ rare disease candidate, KalVista Pharmaceuticals' angioedema asset and Omeros’ transplant drug, among others.
Editor's note: This story was updated at 1:30 p.m. ET on Aug. 19 to add a statement from the Department of Health and Human Services.