“Today is a milestone day for children and their families battling Hunter syndrome,” said FDA Commissioner Marty Makary, M.D., M.P.H. “The FDA is capable of doing two things: one, exercising regulatory flexibility; and two, complying with our obligation under the law to approve drugs based on ‘substantial evidence’ of effectiveness. We will continue to do everything we can to accelerate treatments for rare diseases.”

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.

Avlayah, an IV 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.

“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 US, almost exclusively males,” said Acting CDER Director Dr. Tracy Beth Hoeg, M.D., Ph.D. “This accelerated approval was based on a surrogate endpoint: reduction of cerebrospinal fluid heparan sulfate, which the review team determined was reasonably likely to predict Avlayah’s clinical benefit. Heparan sulfate is one of the glycosaminoglycans that accumulates in the body in this disorder and is linked to the organ damage that occurs in early childhood. The drug’s application holder, Denali Therapeutics, is now conducting a randomized clinical trial that is more than 95% 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.”

To support approval, the sponsor submitted results from a phase 1/2 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% average decrease from baseline in CSF HS; the minimum and maximum percent change in CSF HS from baseline were 72% and 98%, respectively. At baseline, no patients had CSF HS levels below the upper limit of normal (ULN); at Week 24, 93% 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, associated with the drug. Patients should start therapy in a health care setting with appropriate medical monitoring and support measures. The most common side effects of Avlayah include upper respiratory tract infection, ear infection, fever, anemia, cough, vomiting, diarrhea, rash, COVID-19, runny nose, nasal congestion, fall, headache, skin abrasion, and hives. Due to the risk of anemia, hemoglobin levels should be obtained at baseline, at three months after starting therapy, and then periodically as clinically indicated. Health care providers should treat anemia based on clinical judgment. Due to the risk of membranous nephropathy (a kidney disease), kidney function and urine protein levels should be monitored. If kidney disease is suspected, patients should have an appropriate evaluation and therapy.

Avlayah received breakthrough, fast track, priority review, and orphan drug designations and accelerated approval for this indication. The approval was granted to Denali Therapeutics.

Source:

U.S. Food and Drug Administration. FDA Approves Drug to Treat Neurologic Manifestations of Hunter Syndrome [Internet]. Silver Spring (MD): FDA; 2026 Mar 25 [cited 2026 Mar 24]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome