The FDA cited manufacturing issues but did not flag problems with Ultragenyx’s data package for UX111, with the biotech noting that the regulator found its neurodevelopmental findings for the gene therapy to be “robust.”
The FDA declined to approve Ultragenyx’s investigational in vivo gene therapy UX111, being proposed for the treatment of Sanfilippo syndrome type A. The decision, announced Friday, capped off a tough week for the California biotech, which had just announced disappointing results for another asset on Wednesday.
Ultragenyx plunged nearly 26% as the week closed. The company was trading at less than $30 as markets closed on Friday, versus nearly $40 when it opened on July 7.
In a note to investors on Monday morning, analysts at William Blair called the rejection an “unfortunate sentiment hit” for Ultragenyx, however noting that while the exact timeline for the application’s resubmission remains “unclear,” the FDA’s concerns around UX111 “could ultimately be resolved in a timely manner.”
The FDA’s complete response letter was focused on manufacturing issues “not directly related to the quality of the product,” Ultragenyx announced on Friday. The regulator is seeking more information regarding “improvements” in “certain aspects” of chemistry, manufacturing and controls related to UX111.
“The company believes that these observations are readily addressable,” Ultragenyx said on Friday, noting that the company will work to resolve these issues in “the next few months.” Ultragenyx plans to resubmit an approval application and anticipates another six-month review period for UX111.
Ultragenyx emphasized on Friday that the FDA did not cite problems with its data package for UX111. “The FDA has acknowledged that the neurodevelopmental outcome data provided to date are robust and the biomarker data provide additional supportive evidence,” according to the biotetch.
Also known as mucopolysaccharidosis type III, Sanfilippo syndrome is a rare and genetic metabolic disorder that typically involves a wide variety of manifestations. Patients can suffer from a broad range of neurological symptoms, including language delays, developmental delays and progressive intellectual disability. Sanfilippo syndrome symptoms grow worse over time, ultimately leading to death.
Sanfilippo syndrome affects around 1 in every 50,000 to 250,000 people worldwide, of which type A is the most common. Ultragenyx’s gene therapy UX111 works by delivering a functioning copy of the SGSH gene, which in Sanfilippo syndrome is pathologically mutated. UX111 was originally developed by Abeona Therapeutics but was bought by Ultragenyx in May 2022 in exchange for up to 10% of tiered royalties and commercial milestones.
The asset’s FDA rejection came just two days after Ultragenyx released seemingly negative news for its asset UX143, a monoclonal antibody, designed in collaboration with Mereo BioPharma, to boost bone formation. The Phase II/III Orbit trial in osteogenesis imperfecta will proceed to its final analysis, suggesting that the study failed to meet an efficacy threshold that would have otherwise warranted its early termination, according to William Blair analysts at the time.
Compounding Ultragenyx’s troubles, securities litigation firm Levi & Korsinsky launched an investigation into the company over “possible violations of federal securities laws,” according to a news release on Thursday. The firm has not yet revealed what these alleged violations could be.
