FDA
FDA approves Avlayah to treat neurologic manifestations of Hunter syndrome
Brand name: Avlayah
Generic name: tividenofusp alfa-eknm
Manufacturer: Denali Therapeutics
Approval date: March 25, 2026
Avlayah (tividenofusp alfa-eknm) was granted accelerated approved for the treatment of neurologic manifestations of Hunter syndrome (Mucopolysaccharidosis type II, MPS II) in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment.
Hunter syndrome is an inherited X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS), a lysosomal enzyme, that degrades heparan sulfate (HS) and dermatan sulfate (DS), the two primary glycosominoglycans (GAGs) in the lysosome. Insufficiency of IDS leads to accumulation of GAGs, including HS and DS, and subsequent lysosome dysfunction in multiple organs and tissues, including the CNS. Avlayah (tividenofusp alfa-eknm) provides an exogenous source of IDS. The drug uses a proprietary transport vehicle platform, enabling it to cross the blood–brain barrier for delivery into the CNS, as well as peripheral tissues.
Efficacy
This indication was approved based on a surrogate endpoint: reduction of cerebrospinal fluid heparan sulfate (CSF HS) observed in patients treated with Avlayah. Continued approval is contingent upon verification of clinical benefit in a phase 2/3 confirmatory trial (COMPASS), which is currently enrolling patients.
Accelerated approval was supported by the results from a phase 1/2 multi-cohort, single-arm, open-label trial (NCT04251026) which enrolled 47 male pediatric patients with Hunter syndrome aged 3 months to 13 years (median age, 5 years). The study population consisted of 27 White (57%), 4 Black or African American (9%), 4 Asian (9%), 3 who were more than one race (6%), 1 of another race (2%), and 8 of an unknown race (17%). Ethnicity consisted of 7 patients who were Hispanic or Latino (15%), 38 who were Not Hispanic or Latino (81%), and 2 of an unknown ethnicity (4%). Participants received Avlayah (tividenofusp alfa‑eknm) as a weekly IV infusion; the most common dose (57% of patients) was 15 mg/kg once weekly.
At week 24, the 44 patients with measurements had a 91% average decrease from baseline in CSF HS (95% confidence interval, 89%-92%); the minimum and maximum percent changes 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.
Safety
Most common adverse reactions (≥20%): infusion-associated reactions, upper respiratory tract infection, ear infection, pyrexia, anemia, cough, vomiting, diarrhea, rash, COVID-19, rhinorrhea, nasal congestion, fall, headache, skin abrasion, and urticaria. The prescribing information for Avaylah also includes a boxed warning for hypersensitivity reactions, including anaphylaxis, and warnings regarding anemia and membranous nephropathy.
Recommended dose
Avlayah is given once weekly as an IV infusion over approximately 4 hours. Initiate Avlayah in a healthcare setting using the dose escalation regimen described in the prescribing information. For pediatric patients weighing at least 5 kg, the recommended maintenance dose is 15 mg/kg via IV infusion once weekly.
Sources:
(2026, March 25). Denali Therapeutics Announces U.S. FDA Approval of Avlayah (tividenofusp alfa-eknm) for Treatment of Hunter Syndrome (MPS II). [Press release]. https://investors.denalitherapeutics.com/news-releases/news-release-details/denali-therapeutics-announces-us-fda-approval-avlayahtm
(2026, March 25). FDA Approves Drug to Treat Neurologic Manifestations of Hunter Syndrome. [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome
Avlayah (tividenofusp alfa-eknm). [Package insert]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/761485s000lbl.pdf. Revised March 2026. Accessed March 30, 2026.