NEW YORK – The US Food and Drug Administration has accepted Ultragenyx Pharmaceutical's biologics license application (BLA) for its Sanfilippo syndrome type A (MPS IIIA) gene therapy, the Novato, California-based company said Tuesday. The company is further seeking accelerated approval for the treatment.
The FDA, which granted the BLA priority review, expects to review the application and issue a decision on the gene therapy, dubbed UX111, by Aug. 18.
Ultragenyx's BLA submission was based on data from the ongoing pivotal Phase I/II/III Transpher A trial and long-term follow-up studies, in which the firm has observed that patients treated with UX111 experienced rapid and sustained decreases in levels of heparan sulfate (HS) in cerebrospinal fluid (CSF), across ages and stages of disease progression.
Ultragenyx and the FDA reached an agreement last year on using HS CSF as a surrogate endpoint for an accelerated approval. Since patients with MPS IIIA have an abnormal accumulation of HS in their brain, which leads to neurodegeneration and early death, HS CSF was deemed a biomarker reasonably likely to predict the gene therapy's clinical benefit.
"By reaching alignment with the [FDA] on a path forward for accelerated approval in neuronopathic MPS diseases, our UX111 program could serve as a step towards advancing drug development across multiple metabolic diseases of the brain," Ultragenyx CEO and President Emil Kakkis said in a statement.
Patients in the Transpher A trial also experienced improvement in cognition and communication compared to natural history data, which was also correlated with reductions in HS CSF.
The most common treatment-related adverse events reported in the clinical trial were elevations in liver enzymes, most of which were mild or moderate in severity and all of which resolved. UX111, which is administered intravenously, is an in vivo gene therapy that uses an adeno-associated virus serotype 9 vector to deliver a functional copy of the SGSH gene, mutations in which cause MPS IIIA, a rare lysosomal storage disorder. Ultragenyx acquired global rights to UX111 from Abeona Therapeutics in 2022.
The FDA has said that it is not planning to hold an advisory committee meeting to discuss the BLA, according to Ultragenyx.