FDA Approves Drug to Treat Hunter Syndrome

The U.S. Food and Drug Admini-stration (FDA) approved Avlayah (tividenofusp alfa-eknm) to treat certain individuals with Hunter syndrome (Mucopolysaccharidosis type II or MPS II). Avlayah, an intravenous infusion given once weekly, is approved to treat neurologic manifestations of Hunter syndrome when the medication is started in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment.

Hunter syndrome is a rare inherited lysosomal disorder in which sugar molecules called glycosaminoglycans build up within the cells’ lysosomes. This substrate accumulation affects physical and mental development by causing abnormalities in the skeleton, heart, respiratory system, brain and other organs.

Approval is based on results from a Phase I/II multi-cohort, single-arm, open-label trial that enrolled 47 pediatric patients with Hunter syndrome aged 3 months to 13 years. In the trial, Avlayah significantly reduced cerebrospinal fluid heparan sulfate (CSF HS), a type of glycosaminoglycan. The 44 patients with measurements at week 24 had a 91 percent average decrease from baseline in CSF HS; the minimum and maximum percent change in CSF HS from baseline were 72 percent and 98 percent, respectively. At baseline, no patients had CSF HS levels below the upper limit of normal (ULN); at week 24, 93 percent of Avlayah-treated patients with CSF measurements had CSF HS levels below the ULN. Avlayah’s labeling includes a boxed warning for allergic reactions, including anaphylaxis.

“Avlayah is the first product approved to address neurologic complications of Hunter syndrome, a very rare and often severe X-linked disorder in children, affecting about 500 people in the U.S., almost exclusively males,” said Acting Center for Drug Evaluation and Reserch Director Tracy Beth Hoeg, MD, PhD. “The drug’s application holder, Denali Therapeutics, is now conducting a randomized clinical trial that is more than 95 percent enrolled to evaluate the clinical benefit of this product. In the meantime, families with young children with Hunter syndrome will have access to a product that may favorably alter the course of the disease at the crucial time in life when there is the greatest potential for benefit.”