FDA approves the first gene therapy for children with Sanfilippo syndrome type A

The U.S. Food and Drug Administration licensed Fayuvi, proper name rebisufligene etisparvovec-hopf, on 17 September 2026 as the first approved treatment for children with mucopolysaccharidosis type IIIA, also known as Sanfilippo syndrome type A. The therapy comes from Ultragenyx Pharmaceutical, Inc. and is delivered as a single intravenous infusion of an adeno-associated virus serotype 9 vector carrying a functional SGSH gene.

Children with MPS IIIA lack the enzyme sulfamidase, so heparan sulfate accumulates in cells including neurons. The therapy enables the body to produce the missing enzyme. MPS IIIA is a rare inherited lysosomal storage disorder that causes progressive neurodevelopmental deterioration: affected children develop apparently normally, then lose cognitive, language and developmental abilities, typically in early childhood. Before this approval there was no disease-modifying therapy, only supportive care.

The evidence came from an open-label, single-arm, multicentre clinical study in which change in cognitive score was assessed between the ages of two and five years, the critical developmental window. Patients treated with Fayuvi "maintained or improved cognitive function compared to an untreated historical control cohort," diverging from the expected natural history of the disease. There was no concurrent randomised comparator; the benchmark was the historical cohort.

Kyle Diamantas, J.D., Acting FDA Commissioner, said: "Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A," and that the approval "marks a historic moment for children and families living with MPS IIIA." Karim Mikhail, B. Pharm., M.S., Director of the Center for Biologics Evaluation and Research, said: "Today's approval of Fayuvi is a meaningful step forward for these children and their families." Megha Kaushal, M.D., M.Sc., Acting Deputy Director of the Office of Therapeutic Products, said the approval "underscores OTP's and FDA's commitment to applying rigorous evidentiary standards."

The approved indication is pediatric patients with mucopolysaccharidosis type IIIA. The product carries Orphan Drug, Fast Track and Breakthrough Therapy designations.

The most common adverse reactions, occurring in more than 5 per cent of patients, are elevated liver enzymes including AST, nausea, vomiting, fever, decreased appetite, reduced white blood cell and platelet counts, and elevated amylase. Important identified risks are thrombotic microangiopathy and the theoretical long-term risk of tumour development from genomic integration of the vector's genetic material. Corticosteroid treatment is required for a minimum of eight weeks after the infusion.

Two facts a reader might expect are absent from the record. The FDA did not disclose the price of Fayuvi, and the number of patients enrolled in the registrational study is not stated in the approval announcement.

The licensure is the third notable FDA gene or cell therapy action of the period. On 30 June 2026 the agency approved Tregzi, from Orca Biosystems, a donor-derived regulatory T-cell immunotherapy that raised one-year chronic graft-versus-host-disease-free survival to 78 per cent against 38.4 per cent in the 187-patient PRECISION-T trial. On 1 July 2026 it extended the CRISPR therapy Casgevy (exagamglogene autotemcel) down to age two for sickle cell disease and transfusion-dependent beta thalassaemia, in a review that took 53 days. On 19 August 2026 it granted accelerated approval to Ultragenyx's Genglycos for glycogen storage disease type Ia.

The unresolved questions are the durability of a single AAV9 dose in the developing brain, whether treatment must be given before symptom onset to preserve cognition, and newborn-screening policy for MPS IIIA. Ultragenyx is required to maintain long-term follow-up for delayed adverse events including malignancy.