Ultragenyx wins surrogate endpoint debate, securing green light to seek FDA approval of gene therapy

Ultragenyx Pharmaceutical's work to get the FDA to recognize a biomarker as a surrogate endpoint looks to have paid off. With the agency agreeing the biomarker is a reasonable surrogate endpoint, Ultragenyx is preparing to file for approval of its Sanfilippo syndrome gene therapy around the end of the year.

A pivotal trial of the UX111 AAV gene therapy was already underway when Ultragenyx acquired global rights to the program from Abeona Therapeutics in 2022. Ultragenyx reported data from the study earlier this year but was unsure whether the FDA would accept a filing based on cerebral spinal fluid (CSF) heparan sulfate (HS). The biotech made its case at a Reagan-Udall Foundation event attended by FDA staff.

Wednesday, Ultragenyx said it had reached an agreement with the agency on the use of the biomarker as a surrogate endpoint for accelerated approval. The biotech now plans to finalize the details of its filing at a meeting with the FDA and apply for approval either late in 2024 or early in 2025. 

Ultragenyx intends to base the submission on data from the ongoing pivotal study of UX111. In February, the rare disease specialist reported that levels of CSF HS fell within one month after treatment with the gene therapy. Ultragenyx reported declines in the biomarker in all 17 people with Sanfilippo, a fatal lysosomal storage disease also known as MPS IIIA, in its modified intention-to-treat group. 

The biotech correlated reductions in CSF HS exposure to changes in cognitive function. When looking at cognitive function, Ultragenyx said it saw “a positive rate of change indicating either stability or gains from baseline in 16 of the 17 patients during the expected window of plateau into decline.”

Ultragenyx’s filing will show whether the FDA views the biomarker results and signs of clinical efficacy as enough for accelerated approval. But, while that big test is yet to come, securing the green light to file for approval is still another milestone in Ultragenyx’s push to quickly expand its portfolio of approved drugs. 

The biotech plans to file for approval of its DTX401 gene therapy in glycogen storage disease type Ia next year and is closing in on phase 3 data for its brittle bone disease drug setrusumab. Winning approval for the candidates, and securing the resulting revenues and priority review vouchers, is part of Ultragenyx’s plan for becoming profitable by 2026.

Bringing UX111 to market will also increase Ultragenyx’s outgoings, though. The company will pay Abeona up to $30 million in commercial milestones following regulatory approval of the product. Abeona is also in line to receive tiered royalties of up to 10% on net sales. Ultragenyx began a public offering of up to $350 million of shares of its common stock after reporting the update on UX111.