Ultragenyx reported a Phase 3 failure for apazunersen (GTX-102) in Angelman syndrome, missing both the primary and key secondary endpoints in its Aspire trial. The antisense oligonucleotide did not achieve the targeted change from baseline in the Bayley-4 Cognitive raw score, nor the key secondary endpoint tied to the Multidomain Responder Index. The setback triggered renewed scrutiny around endpoint selection in Angelman, a condition where cognition and functional outcomes can be difficult to quantify in clinical trial design. Ultragenyx said it will evaluate next steps and pursue significant expense reductions in response to the result. The news follows earlier optimism from developmental data that had raised expectations for a potential breakthrough in a rare disease category with limited treatment options. For other developers pursuing similar mechanisms in Angelman, the readout raises the bar for confirmatory evidence and may shift how sponsors structure endpoints and responder definitions in future programs.