Hunter Syndrome Brain Penetrating Treatment, New FDA Approval After 20 Years

US biotech company Denali Therapeutics Inc. (DNLI) has received FDA accelerated approval for AVLAYAH, an intravenous enzyme replacement therapy engineered to cross the blood-brain barrier, to treat neurological manifestations in pediatric Hunter syndrome patients weighing at least 5 kg.

The approval rests on a surrogate endpoint showing reduced heparan sulfate levels in cerebrospinal fluid and marks the first new treatment option for Hunter syndrome in roughly 20 years. Continued approval will depend on results from the ongoing global Phase 2/3 COMPASS trial. Alongside the approval, the FDA awarded Denali a Rare Pediatric Disease Priority Review Voucher. The company is now preparing to launch AVLAYAH in the U.S., enhance patient access through Denali Patient Services, and host an investor conference call and webcast.

On April 3, Denali announced it had regained worldwide rights to its frontotemporal dementia candidate DNL593 after ending its collaboration with Takeda, and plans to advance clinical development with key Phase 1/2 data expected by year-end. Earlier, on March 27, Denali secured approximately $200 million (about KRW 270 billion) by terminating its synthetic royalty agreement with Royalty Pharma, funding AVLAYAH’s commercialization and subsequent pipeline development.

Headquartered in South San Francisco, California, Denali Therapeutics is a clinical-stage biotech company developing treatments for central nervous system and lysosomal storage disorders—including Alzheimer’s disease, Parkinson’s disease, and Hunter syndrome. Leveraging its TransportVehicle blood-brain barrier platform, the company is expanding a portfolio of brain-penetrant enzyme and antibody therapies as it prepares to enter the neurodegenerative and rare disease markets.