Denali Therapeutics announced primary analysis results from a Phase 1/2 study of tividenofusp alfa (DNL310) in 47 participants with Hunter syndrome (MPS II). Long-term data show sustained biomarker reductions, improvements in hearing, cognition, and adaptive behavior, and a generally well-tolerated safety profile over a median follow-up of two years and up to four years. Denali plans to submit a Biologics License Application (BLA) for accelerated approval in early 2025, aiming for a U.S. launch in late 2025 or early 2026.
This development is potentially transformative for individuals with Hunter syndrome, a rare genetic disease with limited treatment options. Current treatments only partially address physical symptoms and do not cross the blood-brain barrier, leaving cognitive and behavioral impairments unaddressed. Tividenofusp alfa, engineered to deliver the IDS enzyme across the blood-brain barrier, offers a potential solution for the full spectrum of Hunter syndrome manifestations, potentially improving the quality of life for those affected.
The Phase 1/2 study achieved substantial reductions in key disease biomarkers in the central nervous system and periphery. This included normalization of cerebrospinal fluid and urine heparan sulfate, and neurofilament light, a marker of neurodegeneration. Clinically, improvements were seen in liver volume, hearing thresholds, adaptive behavior, and cognition. Most treatment-related adverse events were mild or moderate, primarily infusion-related reactions, anemia, vomiting, fever, respiratory infections, and rash. Serious adverse events were reported in a small percentage of participants and were manageable.
The positive long-term data and upcoming BLA submission position tividenofusp alfa as a promising potential therapy for Hunter syndrome. If approved, it could significantly alter the treatment landscape for this rare disease, addressing unmet needs for a therapy that targets both physical and neurocognitive symptoms. This progress also holds implications for Denali’s broader lysosomal storage disease portfolio, potentially accelerating the development of similar therapies for other conditions like Sanfilippo syndrome Type A.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
