Ultragenyx Shares Plunge Over 40% After Angelman Syndrome Drug Fails Phase 3 Trial

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) shares fell over 40% in after-hours trading Wednesday after the company announced its experimental drug for Angelman syndrome failed a pivotal late-stage trial. The company stated that the Phase 3 Aspire study of apazunersen did not achieve its primary or key secondary endpoints.

Trial Fails to Meet Endpoints

The study's primary goal was to show a significant change from the baseline in the Bayley-4 cognitive raw score, a measure of cognitive development. According to Ultragenyx, the trial did not meet this endpoint.

Additionally, the study missed its key secondary endpoint, which was the net response in the Multidomain Responder Index (MDRI). The company reported there were no meaningful differences between the groups treated with apazunersen and the control group to support the drug's efficacy. The safety profile observed in the trial was consistent with earlier Phase 1/2 results.

Company to Reassess Strategy

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Following the trial's failure, Ultragenyx said it will evaluate the entire apazunersen program and decide on its future. The company also signaled a strategic shift, stating it plans to "define and implement significant expense reductions" to focus on supporting its growing commercial business.

Setback for Angelman Syndrome Treatment

The outcome is a significant setback for patients with Angelman syndrome, a rare neurogenetic disorder with no currently approved therapies. The condition affects an estimated 60,000 people in commercially accessible regions. Apazunersen, an antisense oligonucleotide therapy, was designed to address the root genetic cause of the disorder.

The therapy had previously received multiple expedited designations from the U.S. Food and Drug Administration, including Breakthrough Therapy, Orphan Drug, and Fast Track designations, underscoring the high unmet medical need and the initial promise of the treatment.