The discovery of a tumor in a patient who received REGENXBIO’s gene therapy for Hurler syndrome prompted the FDA to place a hold on that program along with the company’s Hunter syndrome program, which is awaiting an FDA decision on or before Feb. 8.
The FDA has placed a clinical hold on two of REGENXBIO’s rare disease programs after the discovery of a tumor in a patient potentially linked to one of the gene therapies.
The holds could potentially overlap with an upcoming PDUFA date for REGENXBIO’s gene therapy for Hunter syndrome on Feb. 8. This development could therefore provide an opportunity for Denali Therapeutics, which is gearing up for an FDA decision for its own Hunter treatment in April, to be first to market. Shares of REGENXBIO are down 19% in Wednesday morning trading to $10.86.
The REGENXBIO patient in question is an asymptomatic five-year-old who received the company’s gene therapy RGX-111 four years ago for the treatment of Hurler syndrome, according to a company statement Wednesday. During an MRI, doctors discovered an intraventricular central nervous system tumor, a growth in a fluid-filled empty space in the brain.
A genetic analysis of a sample of the tumor showed that an AAV vector, which is used to deliver RGX-111, had integrated into its genome, leading to a mutation in a known cancer-causing gene. A definitive link between the vector and the cancer has not been established, and REGENXBIO said that an “investigation to determine if this SAE [severe adverse event] is drug related is ongoing.”
In tandem, the FDA also placed a hold on REGENXBIO’s RGX-121, a gene therapy being developed for Hunter syndrome, due to similarities in the two products, the patient populations and “shared risk between the clinical studies.” Both Hurler syndrome and Hunter syndrome are diseases of lysosomes, and both treatments are AAV-delivered gene therapies. No other tumors have been detected in nine other patients who received RGX-111 or in 32 patients treated with RGX-121.
The holds could delay an FDA decision for RGX-121. “The time to resolution is unclear,” Jefferies analysts wrote in a note to investors on Wednesday, “potentially putting RGX-121’s Feb. 8, 2026 PDUFA at risk.”
Denali Therapeutics, meanwhile, is expecting a decision on its Hunter treatment, tividenofusp alfa, on April 5. Tividenofusp alfa is not a gene therapy but rather an active version of the protein mutated in Hunter syndrome, iduronate 2-sulfatase, fused to a proprietary delivery construct made by Denali.
Denali could be first to market since the hold seems to focus on the AAV tech behind REGENXBIO’s gene therapies, according to Jefferies. In contrast, Denali’s therapy “is non integrating, reversible/monitorable, and mechanistically designed for repeatable enzyme delivery across the [blood-brain barrier],” the analysts wrote.
Results from 11 patients who received RGX-121 in a Phase I/II/III trial showed an 82% reduction in a key Hunter biomarker, herapran sulfate D2S6 in cerebrospinal fluid, over 12 months, according to data reported in September 2025. By comparison, tividenofusp alfa achieved a 95% reduction of the same biomarker in Phase I/II data presented in Feb. 2025. The favorable data, and the roadblocks facing REGENXBIO, could mean a win for Denali.
“We wouldn’t be surprised to see DNLI receive earlier FDA approval,” Jefferies concluded.
