FDA approves Avlayah for Hunter syndrome

Avlayah (tividenofusp alfa-eknm; Denali Therapeutics) has received FDA approval for use in Hunter syndrome patients.¹

This approval follows positive data from a phase 1/2 multicohort, single-arm, open-label trial assessing the outcomes of Avlayah use in Hunter syndrome patients aged 3 months to 13 years. The results highlighted a significant reduction in cerebrospinal fluid heparan sulfate (CSF HS) following Avalayah administration.

“Today is a milestone day for children and their families battling Hunter syndrome,” said FDA Commissioner Marty Makary, MD, MPH. “The FDA is capable of doing 2 things: 1, exercising regulatory flexibility; and 2, complying with our obligation under the law to approve drugs based on ‘substantial evidence’ of effectiveness.”

Clinical trial efficacy and understand Hunter syndrome

There were 47 pediatric patients enrolled in the trial, 44 of whom had week 24 measurements. Among this population, a 91% average decrease was reported in CSF HS since baseline. Investigators also highlighted a minimum percent change in CSF HS since baseline of 72%, alongside a maximum percent change of 98%.

None of the study population reported baseline CSF HS levels below the upper limit of normal. However, this milestone was achieved at week 24 by 93% of patients receiving Avlayah.

Hunter syndrome is defined by a buildup of sugar molecules known as glycosaminoglycans in the cells’ lysosomes. It is a rare inherited lysosomal disorder with potential adverse outcomes including abnormalities in the heart, respiratory system, skeleton, and other organs.

Benefits of Avlayah

Avlayah is a treatment option for this disorder that is given intravenously once per week. If given to patients weighing at least 5 kg in presymptomatic or symptomatic phases prior to advanced neurological impairment, it effectively treats neurologic manifestation of Hunter syndrome.

This approval followed breakthrough, fast track, and orphan drug designations given to Avlayah. Additionally, Denali highlighted that the treatment was awarded a Rare Pediatric Disease Priority Review Voucher.²

“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,” said Tracy Beth Hoeg, MD, PhD, acting director of the FDA’s Center for Drug Evaluation and Research.¹

According to Beth Hong, Hunter syndrome is often severe and is present in approximately 500 US individuals, with a greater prevalence reported in male patients. Avlayah is the first product to receive FDA approval focused on improving neurological outcomes in affected patients and will be further evaluated in a randomized clinical trial that is now more than 95% enrolled.

Safety profile and adverse events

The FDA has highlighted potential allergic reactions from Avlayah use, including drug-related anaphylaxis. To ensure safety, experts recommend that patients start Avlayah in a health care setting with appropriate medical monitoring and support measures.

Upper respiratory tract infection, ear infection, anemia, cough, fever, diarrhea, vomiting, COVID-19, rash, nasal congestion, runny nose, skin abrasion, hives, fall, and headache have been reported as common adverse events from Avlayah. The FDA stated that hemoglobin levels should be assessed in patients taking Avlayah at baseline, 3 months, and as clinically indicated.

Additionally, kidney function and urine protein level monitoring is recommended because of the risk of membranous nephropathy. The FDA noted patients with suspected kidney disease should undergo appropriate evaluation and therapy.

“We will continue to do everything we can to accelerate treatments for rare diseases,” said Makary.

References

1. FDA approves drug to treat neurologic manifestations of Hunter syndrome. News release. FDA. March 25, 2026. Accessed March 25, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome?utm_medium=email&utm_source=govdelivery
2. Denali Therapeutics announces US FDA approval of Avlayah (tividenofusp alfa-eknm) for treatment of Hunter syndrome (MPS II). News release. Denali Therapeutics. March 25, 2026. Accessed March 25, 2026. https://investors.denalitherapeutics.com/news-releases/news-release-details/denali-therapeutics-announces-us-fda-approval-avlayahtm