The US Food and Drug Administration (FDA) granted accelerated approval to Avlayah (tividenofusp alfa-eknm), developed by the American biopharmaceutical company Denali Therapeutics. This is the first drug intended 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 and did not affect cognitive impairment.
The company noted that the price of the drug has been set at $5,200 per 150 mg vial, and therapy will become available in the US shortly. Wedbush, an analytical firm, emphasized that this approval sets a positive precedent for other programs using surrogate endpoints. Denali Therapeutics’ shares rose 8.4% to $22.74 following the announcement.
Avlayah is administered intravenously once a week. It 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—a surrogate marker that, in the FDA’s view, is reasonably likely to predict clinical benefit. Denali Therapeutics is conducting a confirmatory study, and full approval will depend on its results.
The regulatory decision comes at a significant moment amid a tightening of requirements for the approval of drugs for rare diseases led by Vinay Prasad, who is stepping down as head of the Center for Biologics Evaluation and Research (CBER) at the end of April. Prasad has repeatedly spoken out against the use of surrogate endpoints. Avlayah’s prescribing information includes a boxed warning about the risk of severe allergic reactions.
