FDA Approves First Gene Therapy for Sanfilippo Syndrome Type A

The U.S. Food and Drug Administration (FDA) has approved Fayuvi (rebisufligene etisparvovec-hopf), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), more commonly known as Sanfilippo syndrome type A. The rare, inherited condition progressively damages the brain and nervous system, causing children to lose cognitive, language and other developmental abilities over time. Until this approval, treatment options were limited to managing symptoms, with no therapy available that addressed the disease’s underlying cause.

“The approval of Fayuvi marks a historic moment for children and families living with MPS IIIA, which is a disease that has, until now, offered no approved treatment to alter its devastating course,” said Acting FDA Commissioner Kyle Diamantas, J.D.

How the Gene Therapy Works

Fayuvi is administered as a one-time intravenous infusion. It uses a modified, noninfectious virus, an adeno-associated virus serotype 9 (AAV9), to deliver a working copy of the SGSH gene into a patient’s cells. This allows the body to produce sulfamidase, the enzyme that’s missing or deficient in MPS IIIA, enabling proper breakdown of heparan sulfate and reducing its harmful accumulation throughout the body and brain.

Karim Mikhail, B. Pharm., M.S., director of the FDA’s Center for Biologics Evaluation and Research, described the disease’s typical trajectory as one where children develop normally in their earliest years before facing relentless regression. “Parents and clinicians have been waiting far too long for an option,” Mikhail said, calling the approval “a meaningful step forward” both for affected families and for the broader promise of gene therapy in treating rare, devastating diseases.

What the Clinical Data Showed

Fayuvi’s safety and effectiveness were evaluated in an open-label, single-arm, multicenter clinical study involving pediatric patients with MPS IIIA. Researchers measured mean changes in cognitive scores among patients between the ages of 2 and 5. Compared with an untreated historical control cohort, Fayuvi-treated patients maintained or improved cognitive function, a notable divergence from the disease’s expected course of plateau and decline during this critical developmental window.

Megha Kaushal, M.D., M.Sc., acting deputy director of the FDA’s Office of Therapeutic Products, called the result “a significant scientific milestone,” noting that it demonstrates systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutically meaningful levels in pediatric patients.