FDA Approves Avlayah for Neurologic Manifestations of Hunter Syndrome
Key Takeaways
- The FDA granted accelerated approval to Avlayah for pediatric patients with Hunter syndrome to address neurologic manifestations.
- Approval was based on reductions in cerebrospinal fluid heparan sulfate, a surrogate biomarker of disease activity.
- Avlayah is the first therapy approved to target central nervous system involvement in this rare lysosomal disorder.
The Food and Drug Administration (FDA) has granted accelerated approval to Avlayah (tividenofusp alfa-eknm; Denali Therapeutics, South San Francisco, CA) for the treatment of neurologic manifestations of mucopolysaccharidosis type II (MPS II), or Hunter syndrome, in pediatric patients weighing at least 5 kg. The therapy is indicated for use in presymptomatic or symptomatic individuals prior to advanced neurologic impairment.
Hunter syndrome is a rare X-linked lysosomal storage disorder characterized by accumulation of glycosaminoglycans, leading to multisystem involvement including progressive neurologic decline. Avlayah is administered as a once-weekly intravenous infusion and is designed to address central nervous system manifestations of the disease.
Approval was based on data from a phase 1/2, multi-cohort, open-label study that enrolled 47 pediatric patients aged 3 months to 13 years. At 24 weeks, treatment was associated with substantial reductions in cerebrospinal fluid heparan sulfate (CSF HS), a biomarker linked to disease burden. Among 44 patients with available data, mean CSF HS levels decreased by 91% from baseline, with reductions ranging from 72% to 98%. No patients had CSF HS levels below the upper limit of normal at baseline. By week 24, 93% of treated patients achieved levels below this threshold.
The approval was granted under the accelerated approval pathway based on this surrogate end point, which the FDA determined is reasonably likely to predict clinical benefit. A confirmatory randomized clinical trial is ongoing to evaluate clinical outcomes.
Avlayah carries a Boxed Warning for hypersensitivity reactions, including anaphylaxis, and should be initiated in a monitored health care setting. Common adverse events include upper respiratory tract infection, fever, anemia, and gastrointestinal symptoms. Monitoring for anemia and renal complications is recommended during treatment.
Source: U.S. Food and Drug Administration. FDA approves drug to treat neurologic manifestations of Hunter syndrome. Fda.gov. Published 25 March, 2026. Accessed 27 March, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome?utm_medium=email&utm_source=govdelivery