The FDA has granted accelerated approval to Denali Therapeutics’ AVLAYAH™ (tividenofusp alfa‑eknm) for the treatment of neurologic manifestations of Hunter syndrome (mucopolysaccharidosis type II, or MPS II) in pediatric patients weighing at least 5 kilograms who have not yet developed advanced neurologic impairment. AVLAYAH represents the first new FDA-approved therapy for Hunter syndrome in almost two decades and the first in a new class of biotherapeutics designed to cross the blood–brain barrier using the transferrin receptor pathway.
The approval was based on biomarker evidence showing a significant reduction in cerebrospinal fluid heparan sulfate (CSF HS), a surrogate endpoint likely to predict clinical benefit. In a Phase 1/2 study, treatment with AVLAYAH resulted in a 91% reduction in CSF HS from baseline by week 24, with most patients reaching levels typical of individuals without Hunter syndrome. The therapy was generally well tolerated, with infusion-related reactions being the most common adverse event. Continued approval may depend on confirmation of clinical benefit in the ongoing Phase 2/3 COMPASS study.
Hunter syndrome is a rare lysosomal storage disorder caused by a deficiency of the iduronate 2‑sulfatase enzyme, leading to buildup of complex sugars in tissues throughout the body and brain. The disease often results in developmental decline, behavioral challenges, and loss of motor and cognitive function.
AVLAYAH is the first FDA-approved medicine to leverage Denali’s TransportVehicle™ platform, enabling delivery of the therapeutic enzyme to both peripheral tissues and the central nervous system. The drug received a Rare Pediatric Disease Priority Review Voucher in connection with the approval and will be available in the U.S. in the near term.
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