Ultragenyx Pharmaceutical said its Phase 3 Aspire study of apazunersen, an investigational treatment for Angelman syndrome, failed to meet its primary endpoint and key secondary endpoint, prompting the company to review the program and plan significant expense reductions.
The study evaluated apazunersen, also known as GTX-102, in people with Angelman syndrome, a rare neurogenetic disorder associated with cognitive and motor impairment, balance problems, seizures, anxiety and disrupted sleep.
Aspire did not achieve its primary endpoint, a change from baseline in the Bayley-4 cognitive raw score. It also missed its key secondary endpoint, net response on the Multidomain Responder Index, or MDRI.
Ultragenyx said the randomized treatment and control groups were comparable at baseline and consistent with patients studied in Phase 2. The company reported no differences between the groups that would support treatment efficacy on Bayley cognitive scores or MDRI results, whether measured by net response or average changes across the index’s five endpoints.
The safety profile observed in the Phase 3 trial was consistent with findings from Phase 1/2 studies, the company said.
Apazunersen is an antisense oligonucleotide administered intrathecally. It is designed to inhibit expression of UBE3A-AS, which could prevent silencing of the paternally inherited UBE3A gene allele and restore expression of the protein that is deficient in Angelman syndrome.
The therapy has received FDA Breakthrough Therapy, Orphan Drug, Rare Pediatric Disease and Fast Track designations. It has also received Orphan and PRIME designations from the European Medicines Agency.
Ultragenyx said it will evaluate the apazunersen program in light of the Aspire findings and determine its future disposition. The company will also assess planned operations to identify and implement significant cost reductions while continuing to support its commercial business.
Chief Executive Emil Kakkis said the company remains focused on commercial growth, including revenue from the recent approval of GENGLYCOS for glycogen storage disease type Ia, potential approval of UX111 for Sanfilippo syndrome and geographic expansion of existing products.
The company said its commercial foundation is expected to support the pipeline as it works toward profitability in 2027.
Angelman syndrome affects an estimated 60,000 people in commercially accessible geographies. There are no currently approved therapies for the disorder.
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