Shares of Ultragenyx Pharmaceutical plummeted 45%. The sharp decline came after the company revealed that its Phase 3 Aspire study evaluating apazunersen for Angelman syndrome did not meet its main goals.

The trial failed to hit the primary endpoint, which measured the change from baseline in the Bayley-4 cognitive raw score. It also missed the key secondary endpoint of net response in the Multidomain Responder Index. Despite this, the company noted that the safety profile observed in the Aspire study was consistent with earlier Phase 1/2 results.

At the start of the trial, the randomized groups were well-matched and similar to patients from the Phase 2 study. However, no meaningful differences emerged between the treated and control groups. The data showed no support for efficacy in either the Bayley Cognition raw scores or the Multidomain Responder Index when assessing net response or the average changes across the five individual endpoints within the index.

In response to the outcome, Ultragenyx stated it will reassess the apazunersen program and decide on its future. The company also plans to review its operations to identify and put into place substantial cost reductions while continuing to back its expanding commercial business.

Apazunersen is an experimental antisense oligonucleotide therapy given through intrathecal injection. It is designed to target and block the expression of UBE3A-AS, aiming to prevent the silencing of the paternally inherited copy of the UBE3A gene. The therapy had previously received several special designations from the U.S. Food and Drug Administration, including Breakthrough Therapy, Orphan Drug, Rare Pediatric Disease, and Fast Track statuses.

Angelman syndrome is a rare neurogenetic condition resulting from the loss of function of the maternally inherited UBE3A allele. It impacts roughly 60,000 individuals in commercially accessible regions. At present, no approved treatments exist for this disorder.