The New England Journal of Medicine Publishes Phase 1/2 Study of Denali Therapeutics' Tividenofusp Alfa (DNL310) for Hunter Syndrome (MPS II)

Core Insights - Denali Therapeutics announced the publication of results from the Phase 1/2 clinical trial of tividenofusp alfa (DNL310) for Hunter syndrome, with FDA Priority Review for its Biologics License Application expected by April 5, 2026 [1][5] Group 1: Clinical Trial Results - The Phase 1/2 trial demonstrated that tividenofusp alfa significantly reduced central nervous system and peripheral biomarkers of substrate accumulation and neuronal injury, indicating potential for improved clinical outcomes in MPS II [3][4] - Key secondary endpoints showed normalization of heparan sulfate levels in cerebrospinal fluid and urine, with 93% of participants achieving levels within the range of unaffected children at Week 24 [11] - Clinical results included normalization of liver volume, improvement in hearing thresholds, and skill gains in adaptive behavior and cognition [11] Group 2: Treatment Mechanism and Designation - Tividenofusp alfa is designed to cross the blood-brain barrier, addressing both neurological and physical symptoms of Hunter syndrome, which current therapies do not [3][9] - The FDA has granted multiple designations to tividenofusp alfa, including Rare Pediatric Disease Designation, Breakthrough Therapy Designation, Fast Track, and Orphan Drug designations [7][9] Group 3: Ongoing Studies and Future Directions - Denali is conducting the Phase 2/3 COMPASS study to support global approval, comparing tividenofusp alfa with idursulfase [8] - The company is exploring the potential of its TransportVehicle™ platform for delivering other therapeutic agents across the blood-brain barrier, aiming to establish a new class of medicines [4][12]