FDA Grants Accelerated Approval to First Therapy for Neurological Effects of Hunter Syndrome
The FDA has granted accelerated approval to Denali Therapeutics' Avlayah (tividenofusp alfa-eknm), the first therapy targeting neurological symptoms of Hunter syndrome. The approval was based on a surrogate endpoint measuring heparan sulfate reduction in cerebrospinal fluid, with confirmatory study results required for full approval. The global Hunter syndrome treatment market is projected to reach $2.6 billion by 2033.
The US Food and Drug Administration (FDA) has granted accelerated approval to Avlayah (tividenofusp alfa-eknm), developed by Denali Therapeutics. This marks the first drug approved to treat the neurological symptoms of Hunter syndrome (mucopolysaccharidosis II), a rare genetic disorder affecting approximately 500 people in the United States.
Previously, the only enzyme replacement therapy available was Takeda's Elaprase, which addressed only the physical manifestations of the disease and did not affect cognitive impairment. Avlayah is administered intravenously once a week and is approved for the treatment of children with presymptomatic or symptomatic stages of the disease.
The accelerated approval was based on a reduction in heparan sulfate — a sugar molecule that accumulates in the disease and is associated with organ damage — in cerebrospinal fluid. This surrogate marker is considered by the FDA to be reasonably likely to predict clinical benefit. Denali Therapeutics is conducting a confirmatory study, and full approval will depend on its results. Avlayah's prescribing information includes a boxed warning about the risk of severe allergic reactions.
The company has set the price of the drug at $5,200 per 150 mg vial, with therapy becoming available in the US shortly. Following the announcement, Denali Therapeutics' shares rose 8.4%.
The regulatory decision comes amid a tightening of requirements for the approval of drugs for rare diseases. The head of the Center for Biologics Evaluation and Research (CBER) has repeatedly spoken out against the use of surrogate endpoints and is stepping down at the end of April.
The global Hunter syndrome treatment market was valued at approximately US$ 1.5 billion in 2023 and is expected to reach US$ 2.6 billion by 2033, growing at a compound annual growth rate of 5.5%. North America accounts for more than 38% of global revenue, with a market value of approximately US$ 0.5 billion in 2023. Enzyme replacement therapy emerged as the dominant treatment category, capturing more than 76% of the overall market share.
Emerging trends in Hunter syndrome treatment include one-time gene therapy modalities using adeno-associated virus vectors, such as RGX-121, which are being evaluated to deliver a functional IDS gene. Intrathecal enzyme replacement therapy has also been explored to overcome the blood–brain barrier and target central nervous system manifestations, with idursulfase-IT having received orphan drug designation from the FDA in 2009.