Ultragenyx Pharmaceutical has secured standard US approval for Fayuvi (rebisufligene etisparvovec), a self-complementary AAV9 gene therapy administered as a one-time intravenous infusion to deliver a functional SGSH gene and restore sulphamidase enzyme activity in children with mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A.

The programme, originally developed by Abeona Therapeutics before transfer to Ultragenyx, is the first approved treatment for this ultra-rare, lethal lysosomal storage disorder, backed by RMAT, Fast Track, rare paediatric disease and orphan drug status in the US and PRIME plus orphan designation in the EU, with approval resting on the Transpher A trial and long-term follow-up approaching eight years.

The efficacy case is built against natural history rather than placebo: in the modified intention-to-treat group of 17 patients, Bayley-III cognitive raw scores from 24 to 60 months of age were 23.5 points higher than a comparable 27-patient untreated cohort (p<0.0001), while cerebrospinal fluid heparan sulphate fell across ages and sustained biochemical correction supported the clinical signal.

Commercially, Ultragenyx has priced Fayuvi at USD 3.95 million per dose, making it the second-most-expensive medicine globally behind Lenmeldy at USD 4.25 million, with JPMorgan forecasting a USD 200 million to USD 250 million peak in a 3,000 to 5,000-patient commercial-access population.