Drug Discov Ther. 2026;20(5):403-404. (DOI: 10.5582/ddt.2026.01082)

Rebisufligene etisparvovec: The first AAV9-mediated SGSH gene therapy approved for the treatment of mucopolysaccharidosis type IIIA (MPS IIIA)

Pang C, Sun YY, Gao JJ

Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome type A) is a rare lysosomal storage disorder caused by biallelic SGSH pathogenic variants that results in heparan sulfate accumulation and progressive neurodegeneration. Previously, treatment was limited to supportive care. In September 2026, the US Food and Drug Administration approved rebisufligene etisparvovec-hopf (FAYUVI), an adeno-associated virus serotype 9–mediated SGSH gene-addition therapy, for neurological manifestations in pediatric patients with preserved neurodevelopmental function. Evidence was primarily derived from the open-label Transpher A study, which compared 17 early-treated patients with 27 external natural history controls. Between 24 and 60 months of age, the model-estimated difference in the change in Bayley-III cognitive raw score was 23.5 points (95% confidence interval, 17.2–29.9), favoring treatment. Heparan sulfate levels in cerebrospinal fluid decreased by a mean of 57.1% at 24 months. Among patients receiving the recommended dose, elevated liver enzymes (85%) and vomiting (67%) were common; serious adverse events occurred in 18 of 33 patients across all dose levels. The approval of rebisufligene etisparvovec represents a landmark advance in the treatment of MPS IIIA, establishing the first disease-modifying gene therapy for this disorder and demonstrating the therapeutic potential of early intervention. Ongoing follow-up and postmarketing surveillance need to be conducted to establish the therapy's long-term efficacy, durability, and safety.

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