The Food and Drug Administration approved Fayuvi (rebisufligene etisparvovec-hopf), made by Ultragenyx Pharmaceutical, on September 17, 2026, as the first gene therapy for pediatric patients with Sanfilippo syndrome type A. Also called mucopolysaccharidosis type IIIA, or MPS IIIA, it is a rare inherited disease that progressively damages the brain and nervous system. Fayuvi is given as a single intravenous infusion.
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Kyle Diamantas, the acting FDA commissioner, said the approval “marks a historic moment for children and families living with MPS IIIA.” Karim Mikhail, director of the agency’s Center for Biologics Evaluation and Research, called it “a meaningful step forward” for the children and their families. The approval matters because no therapy before it had been designed to change the course of the disease, and the evidence behind it comes with caveats that deserve equal attention.
Fayuvi and the SGSH gene it replaces
Children with MPS IIIA lose cognitive, language and other developmental abilities over time. Before this approval, treatment only managed symptoms, according to the FDA’s announcement. The condition arises when the enzyme sulfamidase is missing or deficient, which lets a molecule called heparan sulfate build up in the lysosomes of cells, including cells in the brain.
Fayuvi uses a modified, non-infectious adeno-associated virus serotype 9, or AAV9, as a delivery vehicle for a working copy of the SGSH gene. Once the gene is inside a patient’s cells, they produce sulfamidase, which allows heparan sulfate to be broken down and reduces its harmful buildup in the body and brain. Megha Kaushal, acting deputy director of the FDA’s Office of Therapeutic Products, said the single-infusion benefit represents a significant scientific milestone.
An open-label trial in children aged 2 to 5
The approval rests on an open-label, single-arm, multicenter study of pediatric patients with MPS IIIA aged 2 to 5. The primary measure was the mean change in cognitive scores, and treated patients maintained or improved cognitive function compared with an untreated historical control group, which the agency described as a divergence from the expected plateau and decline. The FDA release does not state how many children were enrolled, and a study without a concurrent control arm cannot rule out every alternative explanation.
Trade coverage supplies more detail on the biomarker side. NeurologyLive reported that a long-term update covered 27 patients in the overall efficacy population at the highest dose, with a median reduction of 63.98% in cerebrospinal fluid heparan sulfate from baseline, and that 81.5% of that population and 88.2% of younger patients reached at least a 50% reduction. The drop occurred within the first month and was sustained for up to 8.5 years. Emil Kakkis, chief executive of Ultragenyx, said the long-term results show a “remarkable and unprecedented separation from the natural history.”
Reports of the approval appeared within days: Fierce Pharma covered the approval of Fayuvi for a rare neurodegenerative disorder, and the American Journal of Managed Care carried its own item on September 21. Neither changes the picture the agency itself gives, which rests on a historical comparison and a biomarker.
The comparison is the crux of the evidence. Natural-history cohorts describe how untreated children with the disease tend to develop, and the FDA framed the treated children as diverging from that expected plateau and decline. That is a weaker design than a randomized trial, and it is also the kind of evidence regulators weigh when a disease is rare, progressive and without an approved therapy aimed at its course. The same logic explains why the agency tied its description to cognitive scores and not to a cure.
Thrombotic microangiopathy and genome integration
The most common adverse reactions, seen in more than 5% of patients, were increased AST liver enzymes, nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts, and increased amylase. The labelling carries two important warnings: a risk of thrombotic microangiopathy, a condition involving clotting in small blood vessels, and a potential long-term risk of tumors if the inserted genetic material integrates into the genome, a risk shared with other AAV-based gene therapies.
Fayuvi must be given in a health care setting equipped to manage infusion reactions. Patients begin corticosteroids one day before the infusion and continue them for at least eight weeks afterward. The product received Orphan Drug, Fast Track and Breakthrough Therapy designations, programs the FDA describes on its Breakthrough Therapy page. The release does not say whether the approval was an accelerated one.
Several questions remain open in the agency’s announcement: the number of children enrolled, whether the approval is accelerated, and how long the benefit lasts. Families and clinicians will weigh a one-time infusion against the labelled risks of clotting complications and, over the long term, tumors. The infusion also requires a corticosteroid course of at least eight weeks afterward, a practical commitment that sits alongside the clinical questions.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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