FDA approves Fayuvi, the first gene therapy for Sanfilippo syndrome type A
Ultragenyx's one-time AAV9 infusion received standard full approval for children with MPS IIIA, and the company received a priority review voucher.
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The U.S. Food and Drug Administration on September 17 approved Fayuvi (rebisufligene etisparvovec-hopf), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. In a filing with the Securities and Exchange Commission, Ultragenyx Pharmaceutical says the FDA granted standard full approval, that the product is also known as UX111, and that it is the company's second gene therapy approval.
The disease and the therapy
The FDA describes MPS IIIA as a rare inherited disease that progressively damages the brain and nervous system, so that children lose cognitive, language and other abilities over time. Until this approval, treatment was limited to managing symptoms.
Fayuvi is a one-time intravenous infusion. It uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a working copy of the SGSH gene, so that cells can make sulfamidase, the enzyme that is missing or deficient in MPS IIIA. The enzyme breaks down heparan sulfate, which otherwise builds up in the body and brain.
The evidence
According to the FDA, an open-label, single-arm, multicenter study measured mean changes in cognitive scores in patients aged 2 to 5 years. Treated patients maintained or improved cognitive function compared with an untreated historical control cohort.
The FDA lists the most common adverse reactions as increased liver enzymes (AST), nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts, and increased amylase. Warnings include thrombotic microangiopathy and, as with other AAV gene therapies, a potential long-term risk of tumor development if the inserted genetic material integrates into the genome. All patients receive corticosteroids from one day before the infusion until at least eight weeks after it.
Designations and voucher
Fayuvi had Orphan Drug, Fast Track and Breakthrough Therapy designations. Ultragenyx says it received a Priority Review Voucher with the approval.
What to watch
The FDA announcement does not name a registry number for the study. On ClinicalTrials.gov, Ultragenyx sponsors a Phase 1/2/3 gene transfer trial of scAAV9.U1a.hSGSH in MPS IIIA (NCT02716246) and a long-term follow-up study of patients from its MPS IIIA gene therapy trials (NCT04360265). The follow-up study lists an estimated 41 participants, cognitive scores over time among its primary outcomes, and an estimated primary completion in August 2027.