Hunter Syndrome Treatment Crossing the Blood-Brain Barrier Receives New FDA Approval After 20 Years

Denali Therapeutics Inc. (NASDAQ: DNLI) announced that AVLAYAH™, its intravenous enzyme replacement therapy, has received accelerated approval from the U.S. Food and Drug Administration to treat the neurological manifestations of pediatric Hunter syndrome. This approval marks the first drug cleared using Denali’s TransportVehicle blood–brain barrier delivery platform and the first new Hunter syndrome therapy in nearly 20 years. The FDA’s decision was based on a surrogate endpoint showing reduced heparan sulfate levels in cerebrospinal fluid, and continued approval will depend on the results of the ongoing global Phase 2/3 COMPASS clinical trial. The agency also awarded Denali a Rare Pediatric Disease Priority Review Voucher. Denali plans to begin U.S. supply of AVLAYAH and launch a patient support program shortly, and will host an investor conference call to outline its launch strategy and platform expansion plans.

Since 2025, Denali has been preparing for the commercial launch of its Hunter syndrome treatment, including building a large-scale biologics manufacturing facility in Salt Lake City to secure in-house production capacity. In the same year, its ALS candidate DNL343 failed to meet the primary endpoint in the HEALEY ALS Platform Phase 2/3 trial. Denali is now reshaping its development strategy based on additional data such as biomarkers and subgroup analyses.

Listed on the Nasdaq, Denali focuses on therapies for neurodegenerative and lysosomal storage diseases. Its proprietary TransportVehicle platform delivers antibodies, enzymes and oligonucleotides—molecules that normally cannot cross the blood–brain barrier—directly into the brain. Several pipeline programs, including a Parkinson’s disease LRRK2 inhibitor, are being co-developed with global pharma partners, while Denali is expanding its platform to target Alzheimer’s disease, Pompe disease and Gaucher disease.