FDA approves Denali’s Avlayah as first Hunter Syndrome treatment for brain health

USA—The U.S. Food and Drug Administration has approved Denali Therapeutics’ enzyme replacement therapy, tividenofusp alfa—now branded as Avlayah.

This now makes Avlayah the first treatment for Hunter syndrome capable of addressing the disease’s debilitating cognitive symptoms.

The FDA granted accelerated approval based on a reduction of cerebrospinal fluid heparan sulfate, a biomarker the agency determined was reasonably likely to predict clinical benefit.

Tracy Beth Høeg, acting director of the FDA’s Center for Drug Evaluation and Research, confirmed the approval on March 25, noting its significance for patients who have long faced limited options.

Why this approval stands apart

The decision comes after a February rejection of a competing Hunter syndrome gene therapy from Regenxbio, which the FDA turned down over concerns about patient population definition, trial design, and its reliance on a single heparan sulfate measure.

Denali, by contrast, measured multiple forms of heparan sulfate and submitted longer-term clinical data, factors analysts at Jefferies had flagged as key differentiators.

Analysts at Leerink Partners noted that Avlayah’s approval effectively puts to rest lingering doubts about whether the FDA would accept heparan sulfate as a valid surrogate endpoint, given that the label explicitly cites cerebrospinal fluid heparan sulfate levels as the approval basis.

Patient advocates respond

The approval carries deep emotional weight for the rare disease community, which recently staged a mock funeral outside the FDA to protest a wave of rejections affecting patients with conditions including Hunter syndrome.

Terri Klein, president and CEO of the National MPS Society, called the outcome a testament to science and advocacy working in concert.

Hunter syndrome, or MPS II, results from a deficiency of the enzyme iduronate-2-sulfatase, leading to the accumulation of large sugars to toxic levels.

Roughly 70% of patients develop severe neurological complications and face a lifespan of approximately 15 years.

Existing therapies cannot cross the blood-brain barrier, leaving cognitive decline unaddressed — until now.

Clinical data and commercialization

Approval rested on data from an open-label Phase 1/2 trial involving 47 patients, in which Avlayah normalized heparan sulfate levels and reduced markers of neuronal injury.

Patients also maintained or improved scores in behavior, cognition, and hearing.

Denali plans to make Avlayah available across the U.S. within two weeks at a list price of USD 5,200 per 150-milligram single-use vial, with co-pay assistance available for eligible commercially insured patients.

The company also received a rare pediatric disease priority review voucher alongside the approval.

A Platform with broader ambitions

Avlayah’s approval validates Denali’s blood-brain barrier shuttle technology, which the company now applies across five clinical programs targeting Alzheimer’s disease, Parkinson’s disease, and Sanfilippo syndrome type A, among others.

 Denali CEO Ryan Watts described the approval as proof that delivering large molecules across the blood-brain barrier — long considered one of biotech’s hardest problems — is now achievable.