FDA Approves Ultragenyx Gene Therapy for Sanfilippo Syndrome Type A

Rare Daily Staff

The U.S. Food and Drug Administration has approved Ultragenyx Pharmaceutical’s one-time gene therapy, Fayuvi, for pediatric patients with the rare lysosomal storage disorder Sanfilippo syndrome type A.

Fayuvi is the first approved treatment intended to alter the course of the rare, progressive neurodevelopmental disorder. The therapy is approved for children with mucopolysaccharidosis type IIIA, or MPS IIIA.

Sanfilippo syndrome type A, or MPS IIIA, is an inherited condition that progressively damages the brain and nervous system, causing affected children to lose cognitive, language, and other developmental skills. Previously, care focused on managing symptoms rather than addressing the disease’s underlying cause.

Fayuvi uses adeno-associated virus serotype 9, or AAV9, to deliver a functional copy of the SGSH gene through a single intravenous infusion. The gene is intended to enable patients’ cells to produce sulfamidase, an enzyme that is deficient or absent in children with MPS IIIA. Without sufficient sulfamidase, heparan sulfate accumulates in lysosomes, potentially causing damage throughout the body and brain.

“Fayuvi marks a historic moment for children and families living with MPS IIIA,” acting FDA Commissioner Kyle Diamantas said in the agency’s announcement. “Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A.”

The FDA based its decision on an open-label, single-arm, multicenter clinical study of children ages 2 to 5 with MPS IIIA. In the study, patients treated with Fayuvi maintained or improved cognitive function compared with an untreated historical control group, according to the agency. The finding diverged from the disease’s expected trajectory, in which children typically plateau and then experience cognitive decline during that developmental period.

The approval is notable for the gene-therapy field because Fayuvi is administered intravenously rather than directly into the central nervous system. FDA officials said the result suggests that systemic AAV9-based delivery can reach the central nervous system at levels capable of producing a meaningful neurodevelopmental effect in pediatric patients.

The most commonly reported adverse reactions, occurring in more than 5 percent of treated patients, included elevated aspartate aminotransferase, or AST; nausea and vomiting; fever; decreased appetite; reduced white blood cell and platelet counts; and increased amylase levels.

The therapy’s label also carries an important warning about thrombotic microangiopathy, a potentially serious condition involving damage to small blood vessels. As with other AAV-based gene therapies, the FDA noted a potential long-term risk that the inserted genetic material could integrate into a patient’s genome and potentially contribute to tumor development.