April 2, 2026 —
Ultragenyx Pharmaceutical has announced that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmitted Biologics License Application (BLA) seeking accelerated approval for UX111 (rebisufligene etisparvovec), an investigational AAV9 gene therapy for Sanfilippo syndrome Type A (MPS IIIA). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of September 19, 2026.
Sanfilippo syndrome Type A is a rare, fatal lysosomal storage disease caused by mutations in the SGSH gene, which lead to deficiency of the sulfamidase enzyme responsible for breaking down heparan sulfate (HS). The resulting accumulation of HS in the brain causes progressive neurodegeneration, developmental decline, and early death, typically by the mid-teens. Currently, no approved therapies exist for this condition.
UX111 is an in vivo AAV9 gene therapy designed to deliver a functional copy of the SGSH gene through a one-time intravenous infusion using a self-complementary AAV9 vector. The therapy enables treated cells to produce the missing enzyme, which can then be secreted and taken up by surrounding cells to restore lysosomal function and reduce heparan sulfate accumulation in the brain.
The BLA submission includes long-term clinical data with up to eight years of follow-up, which were recently presented at WORLDSymposium™ 2026. According to Ultragenyx, the data demonstrate durable treatment effects, including improvements in neurodevelopmental outcomes compared with the natural progression of the disease, along with supportive biomarker data and an acceptable safety profile.
During the previous regulatory review cycle, the FDA acknowledged that the neurodevelopmental outcome data were robust, while biomarker findings provided additional supportive evidence for therapeutic activity.
If approved, UX111 would become the first approved treatment for Sanfilippo syndrome Type A. Manufacturing for the therapy will take place entirely within the United States, including production at Andelyn Biosciences in Columbus, Ohio, and Ultragenyx’s gene therapy manufacturing facility in Bedford, Massachusetts.
The UX111 program has received several regulatory designations aimed at accelerating development, including Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., as well as PRIME and Orphan medicinal product designation in the European Union.
Sanfilippo syndrome Type A is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible regions worldwide. With a median life expectancy of around 15 years, the disease represents a significant unmet medical need. The FDA’s acceptance of the BLA marks a critical step toward potentially delivering the first disease-modifying AAV gene therapy for this devastating pediatric disorder.
