The US FDA has granted standard full approval of Fayuvi (rebisufligene etisparvovec-hopf), an AAV9-based gene therapy from Novato, California-based Ultragenyx Pharmaceutical (Nasdaq: RARE), for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome Type A) in pediatric patients with preserved neurodevelopmental function. Ultragenyx said the therapy is the first approved treatment for this condition. The approval, the company's second gene therapy clearance and sixth overall from the FDA, was accompanied by a Priority Review Voucher.
Fayuvi is administered as a single intravenous dose and is restricted to a network of Qualified Treatment Centers (QTCs). Corticosteroids are required before and after infusion to manage hepatotoxicity risk; post-infusion monitoring for elevated liver enzymes, thrombocytopenia, and thrombotic microangiopathy is mandated by the label. The approval path was not straightforward: the FDA issued a complete response letter (CRL) in July 2025 citing chemistry, manufacturing, and controls issues, before accepting the resubmission with a PDUFA date of September 19, 2026.
The pivotal Transpher A trial enrolled pediatric patients with MPS IIIA and assessed mean change in Bayley-III Cognitive raw score from 24 to 60 months of age. Treated patients in the modified intention-to-treat population (N=17) demonstrated a 23.5-point higher cognitive score compared with an external natural history cohort (N=27), a difference that was statistically significant (p<0.0001). Clinical data now extend to nearly eight years of follow-up, with durable reductions in cerebrospinal fluid heparan sulfate levels observed across all age groups.
Fayuvi delivers a functional copy of the sulfamidase (SGSH) gene via an AAV9 vector, enabling endogenous enzyme expression to clear the accumulated heparan sulfate substrate that drives central nervous system damage in MPS IIIA.