Denali Therapeutics announces primary analysis of Phase 1/2 study in MPS II

Denali Therapeutics (DNLI) announced the primary analysis of the Phase 1/2 study in 47 participants with Hunter syndrome in the 24-week treatment period and additional long-term follow-up of its investigational therapeutic tividenofusp alfa. These data, along with recent Breakthrough Therapy designation, further support the company’s plan to submit a biologics license application in early 2025 for accelerated approval and deliver this potential treatment to the Hunter syndrome community in late 2025 or early 2026. The Phase 1/2 results are being presented this week at the 21st Annual WORLDSymposium conference in San Diego, California. “Our primary analysis in 47 participants with MPS II and the additional long-term data in up to more than four years, support the potential of tividenofusp alfa to address neurocognitive, behavioral, and physical effects for all individuals living with MPS II. We are working as fast as possible to enable tividenofusp alfa as a treatment option for individuals living with MPS II and enable access for them and their families,” said Carole Ho, CMO.The additional Phase 1/2 long-term data demonstrated that treatment with tividenofusp alfa led to substantial and significant reductions to normal and near-normal levels in central nervous system and peripheral biomarkers of disease, including cerebrospinal fluid and urine heparan sulfate, and neurofilament light, a well-established marker of neurodegeneration. Clinical outcomes included normal liver volume after 24 weeks, hearing threshold improvement in all tested frequencies, and skill gains in most participants on measures of adaptive behavior and cognition. Administration of tividenofusp alfa was generally well tolerated in study participants. Most treatment-related adverse events were mild or moderate, including infusion-related reactions, anemia, vomiting, pyrexia, respiratory infections, and rash. Serious TEAEs in three participants were manageable, with resolution or stabilization with continued treatment. One participant discontinued treatment for reasons related to a moderate IRR and other non-treatment-related adverse events.