Ultragenyx resubmits BLA for Sanfilippo syndrome AAV gene therapy

Ultragenyx Pharmaceutical has resubmitted its BLA seeking accelerated approval for its AAV9 gene therapy, UX111, as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA) to the U.S. FDA.

The submission contains substantial longer-term data on multiple measures of neurologic benefit to support an intermediate clinical endpoint for accelerated approval supported further by CSF heparan sulfate and other biomarker data, as agreed with the FDA during the last clinical review. It also includes comprehensive responses to chemistry, manufacturing, and controls (CMC)-related observations outlined in a previously received CRL.

The FDA accepted Ultragenyx’s initial BLA for UX111 back in February 2025, granting it priority review and assigning a PDUFA action date of August 18, 2025. Then, in July 2025, the agency issued a CRL, citing specific CMC-related observations from recently completed manufacturing facility inspections. Ultragenyx said the issues were resolvable as they were “related to facilities and processes and are not directly related to the quality of the product.”

MPS IIIA is a rare fatal lysosomal storage disease that primarily affects the brain and currently has no approved treatment. UX111 is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. UX111 is dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells.