Denali Therapeutics Inc. shares jumped 11.8% midday Wednesday after the U.S. Food and Drug Administration granted accelerated approval for AVLAYAH (tividenofusp alfa-eknm). The product is an enzyme replacement therapy approved to treat neurologic manifestations of Hunter syndrome in pediatric patients who weigh at least 5 kg.
The FDA action is significant on two fronts: it is the first new FDA-approved therapy for Hunter syndrome in nearly 20 years, and it is the first approved medicine intentionally designed to cross the blood-brain barrier by leveraging transferrin receptor technology. AVLAYAH is indicated for mucopolysaccharidosis type II, commonly referred to as MPS II, when started in presymptomatic or symptomatic patients prior to the onset of advanced neurologic impairment.
Hunter syndrome is a rare genetic disorder that affects roughly 500 people in the United States and arises from a deficiency in the iduronate 2-sulfatase enzyme. That enzyme shortfall causes glycosaminoglycans to build up within cells throughout the body, including the brain, producing progressive damage to organs and tissues.
The FDA based its approval on results from a Phase 1/2 clinical trial. By week 24 of treatment, the trial showed a 91% reduction in cerebrospinal fluid heparan sulfate levels from baseline. At that same 24-week time point, 93% of treated patients had cerebrospinal fluid heparan sulfate concentrations that fell within the range observed in individuals without Hunter syndrome.
AVLAYAH is delivered using Denali's TransportVehicle platform. The platform binds to the transferrin receptor to ferry the iduronate 2-sulfatase enzyme to peripheral tissues and into the central nervous system via receptor-mediated transcytosis across the blood-brain barrier. The regimen for AVLAYAH is a once-weekly administration.
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