FDA Approves First Gene Therapy for Rare Childhood Neurodegenerative Disorder

The FDA has approved rebisufligene etisparvovec (Fayuvi) as the first treatment for pediatric patients with mucopolysaccharidosis type IIIA, a fatal genetic condition causing early childhood dementia. The one-time intravenous therapy delivers a functional copy of the SGSH gene via an adeno-associated virus vector to restore enzyme activity and reduce harmful buildup in the brain. In a clinical trial, treated children aged 2 to 5 maintained or improved cognitive function compared with untreated historical controls, with common side effects including liver enzyme elevations, nausea, and fever.

The approval marks a rare success for systemic gene therapy targeting the brain, as AAV9 vectors must cross the blood-brain barrier to deliver the corrective gene. Ultragenyx’s therapy was previously rejected over manufacturing issues, and the final price of $3.95 million reflects the high cost of one-time treatments for ultra-rare diseases. The FDA’s warning about potential tumor risk from gene integration highlights the long-term uncertainty that remains for all such therapies.

Clinical data relied on comparisons to historical controls rather than a placebo group, a common approach in pediatric rare-disease trials where untreated patients would deteriorate rapidly. The therapy is restricted to children with preserved neurodevelopmental function, meaning early diagnosis is critical. Broader newborn screening for MPS IIIA could expand eligibility, but no such program is yet universal.