Ultragenyx stock plunges 40% on failed Angelman trial

Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE) shares fell over 40% in after-hours trading Wednesday following the announcement that its Phase 3 Aspire study for apazunersen in Angelman syndrome failed to meet its primary and key secondary endpoints.

The study did not achieve the primary endpoint of change from baseline in Bayley-4 cognitive raw score nor the key secondary endpoint of net response in Multidomain Responder Index (MDRI). The company said the safety profile observed in Aspire was consistent with Phase 1/2 results.

In the trial, the randomized groups were comparable at baseline and consistent with patients studied in Phase 2. However, there were no differences between the treated and control groups that could support efficacy in the Bayley Cognition raw scores or in the MDRI when examining net response or mean changes of the individual five endpoints included in the MDRI.

Ultragenyx said it will evaluate the apazunersen program in light of this outcome and make a decision on its disposition. The company also plans to assess its planned operations to define and implement significant expense reductions while supporting its growing commercial business.

Apazunersen is an investigational antisense oligonucleotide therapy delivered via intrathecal administration and designed to target and inhibit expression of the UBE3A-AS to prevent silencing of the paternally inherited allele of the UBE3A gene. The therapy had received Breakthrough Therapy Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA.

Angelman syndrome is a rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene, affecting approximately 60,000 people in commercially accessible geographies. There are currently no approved therapies for Angelman syndrome.