The FDA has approved Ultragenyx’s one-time gene therapy Fayuvi (rebisufligene etisparvovec) for Sanfilippo syndrome type A (MPS IIIA), making it the first FDA-approved disease-modifying treatment for this ultra-rare, fatal neurodegenerative disorder. The therapy delivers a functional SGSH gene via an AAV9 vector to reduce buildup of heparan sulfate in the body and brain. The approval is based on an open-label, single-arm pediatric study using historical controls. In patients under age 2 or with earlier-stage disease (n=17), Ultragenyx reported a 23.2-point cognitive benefit (p<0.0001) versus historical benchmarks, alongside improvements across receptive/expressive language and motor function measures. For older, more advanced patients (n=10), the company reported maintenance of communication abilities in most participants, with nine of 10 maintaining walking and self-feeding/eating by mouth. The label includes warnings for thrombotic microangiopathy and potential tumor risks associated with gene therapy. Ultragenyx previously received a complete response letter in 2025 attributed to manufacturing issues, before resubmitting after licensing the asset from Abeona Therapeutics in 2022 and filing the initial BLA in December 2024.