Avlayah Approved for Hunter Syndrome

On March 24, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to Denali Therapeutics’ Avlayah^™ (tividenofusp alfa-eknm) for the treatment of neurologic manifestations of Hunter syndrome (Mucopolysaccharidosis type II, MPS II) when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5kg prior to advanced neurologic impairment. Avlayah is an iduronate 2-sulfatase (IDS) recombinant enzyme replacement therapy (ERT) that delivers IDS to peripheral tissues and the central nervous system (CNS). The therapy incorporates Denali’s proprietary TransportVehicle^™ platform, which was developed to support delivery of biologic therapies across the blood‑brain barrier. The recommended maintenance dose is 15mg/kg once weekly as an intravenous (IV) infusion over approximately four hours. Approval is under the FDA’s accelerated approval pathway, with continued approval contingent upon confirmation of clinical benefit. Avlayah is expected to launch soon at a cost of $5,200 per 150mg vial. Full prescribing information can be found here.

At a Glance

• Brand Drug: Avlayah^™ (tividenofusp alfa-eknm)
• Manufacturer: Denali Therapeutics
• Date Approved: March 24, 2026
• Indication: For the treatment of neurologic manifestations of Hunter syndrome when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5kg prior to advanced neurologic impairment.
• Dosage Forms Available: 150mg as a lyophilized powder in single-dose vials for reconstitution and dilution
• Launch Date: According to Denali Therapeutics, Avlayah will be available shortly.
• Estimated Annual Cost: $270,400
• FDA Designation: Accelerated Approval. Breakthrough Therapy. Orphan Drug. Rare Pediatric Disease Designation. Fast Tracked. The FDA granted Denali a Rare Pediatric Disease Priority Review Voucher (PRV) in connection with this approval.
• Hunter syndrome (MPS II) is a rare, inherited lysosomal storage disorder caused by a deficiency of the iduronate 2-sulfatase (IDS) enzyme, leading to the accumulation of glycosaminoglycans in cells and tissues. The disease can cause developmental delays, organ enlargement, joint stiffness, and in severe cases, progressive neurological decline.
• Hunter syndrome affects approximately 500 people in the US and almost exclusively affects males.
• Approval was based on a phase I/II open-label trial that demonstrated a 91% reduction from baseline in cerebrospinal fluid heparan sulfate (CSF HS) levels by week 24. CSF HS is a surrogate endpoint that is reasonably likely to predict clinical benefit for neurologic manifestations of the disease. Confirmation of clinical benefit is contingent on results from the ongoing phase II/III COMPASS study.
• There is a boxed warning for hypersensitivity reactions, including anaphylaxis. Common adverse events include infusion‑related reactions, infections, fever, anemia, cough, vomiting, diarrhea and rash.
• Approval of Avlayah is limited to treatment initiated prior to advanced neurologic impairment; benefit in older or advanced patients has not been established.
• Takeda’s Elaprase^® (idursulfase) is the only other FDA-approved drug for Hunter syndrome. It is an ERT administered as a weekly IV infusion. Elaprase doesn’t cross the blood-brain barrier and therefore doesn’t treat neurologic symptoms of the disease.
• Regenxbio’s clemidsogene lanparvovec is an IDS gene therapy in development for the treatment of Hunter syndrome. It’s given as a one-time infusion into the brain and is currently on clinical hold.