The Food and Drug Administration (FDA) has placed a clinical hold on two rare disease programs by REGENXBIO after a tumor was found in a patient who had received one of the company’s gene therapies. This development could affect the timeline for approval of REGENXBIO’s gene therapy for Hunter syndrome, with a key FDA decision expected on February 8. The delay may provide an opening for Denali Therapeutics, which is awaiting an FDA decision for its own Hunter syndrome treatment in April.
REGENXBIO’s shares fell by 19% to $10.86 following the announcement. The patient involved is a five-year-old who received RGX-111, REGENXBIO’s gene therapy for Hurler syndrome, four years ago. An MRI revealed an intraventricular central nervous system tumor in the brain. Genetic analysis showed that the AAV vector used to deliver RGX-111 had integrated into the tumor's genome, causing a mutation in a known cancer-related gene. However, it is not yet clear if there is a direct link between the vector and the cancer.
REGENXBIO stated that “an investigation to determine if this SAE [severe adverse event] is drug related is ongoing.” In addition to RGX-111, the FDA also put a hold on RGX-121, another gene therapy developed by REGENXBIO for Hunter syndrome. The agency cited similarities between the products and their target populations as reasons for concern about shared risks between clinical studies.
Both Hurler syndrome and Hunter syndrome are lysosomal diseases treated with AAV-delivered gene therapies. No other tumors have been reported among nine patients treated with RGX-111 or 32 patients who received RGX-121.
Jefferies analysts noted that “the time to resolution is unclear,” and warned that “potentially putting RGX-121’s Feb. 8, 2026 PDUFA at risk.”
Meanwhile, Denali Therapeutics expects an FDA decision on its treatment for Hunter syndrome, tividenofusp alfa, on April 5. Unlike REGENXBIO’s approach, Denali’s therapy delivers an active version of iduronate 2-sulfatase fused to its proprietary delivery construct rather than using gene therapy.
According to Jefferies analysts, Denali could be first to market because its therapy “is non integrating, reversible/monitorable, and mechanistically designed for repeatable enzyme delivery across the [blood-brain barrier].”
Clinical trial data from September 2025 showed that RGX-121 reduced levels of heparan sulfate D2S6—a key biomarker—in cerebrospinal fluid by 82% over twelve months in eleven patients. By comparison, tividenofusp alfa achieved a 95% reduction in Phase I/II data presented earlier in February 2025.
“We wouldn’t be surprised to see DNLI receive earlier FDA approval,” Jefferies concluded.
