Ultragenyx readies US filing for Sanfilippo syndrome gene therapy

Ultragenyx Pharmaceutical has announced its intention to seek accelerated approval for its gene therapy UX111, aimed at treating Sanfilippo syndrome type A (MPS IIIA), a rare and fatal lysosomal storage disorder. The decision follows an agreement with the U.S. Food and Drug Administration (FDA) that levels of heparan sulfate in cerebral spinal fluid (CSF-HS) can serve as a surrogate endpoint in the regulatory filing.

The biotech company plans to finalize the details of its submission to the FDA and aims to file either by late 2024 or early 2025. Ultragenyx acquired the exclusive global rights to UX111, previously known as ABO-102, from Abeona Therapeutics in a $30-million deal in 2022.

"This alignment with the FDA regarding CSF heparan sulfate as a relevant biomarker for accelerated approval is a significant milestone for the community," said Ultragenyx CEO Emil Kakkis. "It opens the door for treatments for all fatal types of neuronopathic mucopolysaccharidoses."

The announcement comes on the heels of clinical data updates from the pivotal TRANSPHER A study, which assessed the one-time intravenous infusion of UX111. As of August 2023, data showed that the treatment led to rapid and sustained reductions in CSF-HS levels. This reduction was associated with stabilization or improvements in cognitive function among 17 patients in the modified intent-to-treat group.

Geena Wang, an analyst at Barclays, noted that the data supported a durable clinical benefit. She also expressed optimism about the FDA's willingness to adopt flexible accelerated approval pathways for rare diseases, based on previous statements from the agency.

In addition to its efforts with UX111, Ultragenyx is preparing regulatory submissions for another gene therapy, DTX401, designed to treat glycogen storage disease type 1a, with plans for submission next year. The company also recently shared longer-term Phase II data for setrusumab, an anti-sclerostin antibody developed in partnership with Mereo BioPharma, aimed at treating osteogenesis imperfecta, a rare inherited brittle bone disease.