FDA decision on UX111 gene therapy for Sanfilippo expected in September
Agency has accepted a resubmitted biologics license application from Ultragenyx
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The U.S. Food and Drug Administration (FDA) is once again considering whether or not it will approve UX111, Ultragenyx Pharmaceutical’s experimental gene therapy for Sanfilippo syndrome type A.
According to Ultragenyx, the FDA has accepted a resubmitted biologics license application (BLA), and a decision from the agency is expected on Sept. 19. If approved, UX111 would become the first approved treatment for Sanfilippo type A.
“The FDA’s acceptance of the BLA for UX111 brings us closer to the possibility of a first-ever therapy for Sanfilippo syndrome Type A — a milestone that we recognize cannot come soon enough for families facing this devastating diagnosis,” Emil D. Kakkis, MD, PhD, CEO and president of Ultragenyx, said in a company press release.
UX111 designed to deliver healthy version of key gene
Sanfilippo syndrome type A is caused by mutations in the SGSH gene. Without a working version of this gene, brain cells cannot break down a molecule called heparan sulfate. Consequently, this molecule builds to toxic levels, ultimately causing brain damage that drives disease symptoms.
UX111 is designed to deliver a healthy version of the SGSH gene to cells, facilitating the clearance of toxic heparan sulfate and slowing the progression of the disease. The investigational gene therapy is administered as a single infusion into the bloodstream.
An ongoing clinical trial, the Phase 2/3 TRANSPHER A (NCT02716246) study, is evaluating UX111 in people with Sanfilippo syndrome type A. The study is still recruiting participants at sites in Spain.
We appreciate the FDA’s prompt acceptance of the resubmission and look forward to working with the Agency throughout its review in order to bring this treatment option to the Sanfilippo syndrome community as quickly as possible.
Available data from TRANSPHER A showed that UX111 treatment reduced heparan sulfate levels in the fluid surrounding the brain and spinal cord, with patients demonstrating improvements in measures of cognition and development relative to what’s expected in untreated Sanfilippo type A patients. Long-term data from a Phase 3 extension study (NCT04360265) suggest these effects were maintained over years after treatment, with more pronounced improvements reported in patients who received gene therapy at younger ages.
In late 2024, Ultragenyx submitted an application to the FDA requesting accelerated approval for UX111 — a type of conditional approval that allows a therapy to be sold based on early data suggesting it will likely benefit patients. Specifically, Ultragenyx sought accelerated approval based on data showing UX111 reduced heparan sulfate levels. If the FDA were to grant conditional approval, Ultragenyx would be required to run additional trials to demonstrate the therapy’s clinical benefit, with long-term approval contingent on those results.
The FDA last year rejected Ultragenyx’s application, citing concerns with the company’s manufacturing process. At the time, the agency didn’t raise any issues related to the clinical trial data but asked Ultragenyx to include updated data in its resubmission. Ultragenyx had already resubmitted the application once, but the FDA requested additional documentation before it would agree to review the application. Now that the documentation has been provided in a third submission, the FDA’s review is underway.
“We appreciate the FDA’s prompt acceptance of the resubmission and look forward to working with the Agency throughout its review in order to bring this treatment option to the Sanfilippo syndrome community as quickly as possible,” Kakkis said.
