The FDA has approved Avlayah for the treatment of neurological manifestations of Hunter syndrome

On March 25, 2026, the FDA approved Denali Therapeutics' Avlayah (tividenofusp alfa-eknm) for the treatment of neurological manifestations of Hunter syndrome (mucopolysaccharidosis type II) in certain pediatric patients. This is the first drug approval in Denali Therapeutics' history. The decision was made under the accelerated approval procedure.

Hunter syndrome is a rare X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. Impaired degradation of glycosaminoglycans leads to their accumulation in tissues and the development of multiorgan damage.

In some patients, the disease is accompanied by progressive damage to the central nervous system, which manifests as cognitive impairment and behavioral disorders. The disease predominantly affects boys.

Avlayah became the first approved therapy targeting the neurological manifestations of MPS II.

Unlike previously used enzyme replacement therapy, the drug was designed for delivery across the blood-brain barrier, which allows it to directly affect the pathological process in the central nervous system.

The basis for accelerated approval was a decrease in heparan sulfate levels in the cerebrospinal fluid, a surrogate biomarker recognized by the FDA as likely to predict the clinical benefit of therapy.

The registration decision requires a confirmatory clinical trial, which should finally confirm the clinical efficacy of the drug.

According to the company and the published results of the Phase 1/2 program, the study, which involved 47 Patients treated with the therapy were accompanied by:

• a significant decrease in heparan sulfate levels in the cerebrospinal fluid
• a decrease in biomarkers of neuronal damage
• early signs of stabilization in a number of neurological and functional indicators

From a scientific and regulatory perspective, this decision is important.

Avlayah approval:

• confirms the clinical applicability of blood-brain barrier drug delivery platforms
• demonstrates the FDA's willingness to use central nervous system biomarkers as surrogate endpoints in orphan diseases
• demonstrates a possible new regulatory model for developing therapies for diseases involving CNS

Source:
FDA approves drug to treat neurological manifestations of Hunter syndrome