The New England Journal of Medicine has published results from the Phase 1/2 clinical trial of tividenofusp alfa (DNL310), an investigational enzyme replacement therapy developed by Denali Therapeutics for Hunter syndrome (mucopolysaccharidosis type II, MPS II), a rare, progressive genetic lysosomal storage disorder. The open‑label study evaluated tividenofusp alfa’s safety, biomarker effects and clinical outcomes in children with MPS II and was released in the journal’s January 1, 2026 issue.
According to the published results, treatment with tividenofusp alfa substantially reduced central nervous system and peripheral disease biomarkers, including cerebrospinal fluid and urine heparan sulfate, often to levels similar to unaffected children, and lowered serum neurofilament light—a marker of neuronal injury—over extended follow‑up. Secondary clinical measures also showed improved liver volume, enhanced hearing thresholds and gains in adaptive behavior and cognition for most participants. The most common treatment‑related events were infusion‑related reactions, which tended to decrease with continued use.
Tividenofusp alfa is engineered by fusing the iduronate‑2‑sulfatase (IDS) enzyme to Denali’s TransportVehicle™ platform, designed to cross the blood‑brain barrier and deliver enzyme replacement throughout the body and into the brain — an attribute not seen with current therapies. The published data support the potential of tividenofusp alfa to address both neurological and somatic manifestations of MPS II.
The U.S. Food and Drug Administration is currently conducting a Priority Review of Denali’s Biologics License Application (BLA) for accelerated approval of tividenofusp alfa, with an expected Prescription Drug User Fee Act (PDUFA) decision date of April 5, 2026. If approved, the therapy could become the first enzyme replacement designed to treat the full spectrum of Hunter syndrome.
