NEW YORK – Ultragenyx Pharmaceutical on Thursday said it has submitted a biologics license application to the US Food and Drug Administration seeking accelerated approval for UX111 as a gene therapy for Sanfilippo syndrome type A (MPS IIIA).
If approved, UX111 would be the first treatment for the rare lysosomal storage disorder to reach the market in the US.
Novato, California-based Ultragenyx earlier this year reached an agreement with the FDA enabling it to use measurements of heparan sulfate (HS) in cerebral spinal fluid (CSF) as a surrogate endpoint for an accelerated approval. This biomarker was deemed reasonably likely to predict the gene therapy's clinical benefit, as patients with MPS IIIA have an abnormal accumulation of HS in their brain, which leads to neurodegeneration and early death.
In the ongoing pivotal Phase I/II/III Transpher A trial, MPS IIIA patients who received UX111 experienced rapid and sustained reductions in HS in CSF, which, over time, were associated with improved long-term cognitive development compared to the decline observed in natural history data, according to Ultragenyx.
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.
Ultragenyx acquired global rights to UX111, previously known as ABO-102, from Abeona Therapeutics in 2022. UX111 is an in vivo gene therapy, administered intravenously, that uses an adeno-associated virus serotype 9 vector to deliver a functional copy of the SGSH gene, mutations in which cause MPS IIIA.
Under the terms of the deal, Abeona is eligible to receive tiered royalties of up to 10 percent on net sales and commercial milestone payments should the gene therapy be approved.
Separately on Thursday, Ultragenyx announced that it treated the first patient in the pivotal Phase III Aspire trial, in which it is evaluating the antisense oligonucleotide treatment GTX-102 in patients with the rare, neurogenetic disorder Angelman syndrome, specifically in pediatric patients with a full maternal UBE3A gene deletion.
Ultragenyx said it is on track to initiate another clinical trial, dubbed Aurora, to evaluate GTX-102 in younger and older patients as well as in patients with other Angelman syndrome genotypes next year.