Ultragenyx said its Phase 3 Angelman syndrome trial, Aspire, failed both the primary endpoint and a key secondary endpoint for apazunersen (GTX-102). The company indicated it will evaluate next steps and has begun laying groundwork for “significant expense reductions,” reflecting the impact of a late-stage setback in a tough-to-treat indication. The failure revives a debate over whether similar antisense or genetic approaches in Angelman syndrome and related disorders can still succeed. Clinicians and industry analysts will now watch how Ultragenyx and peer programs adjust trial design and patient selection.