Ultragenyx said its Phase 3 Angelman syndrome trial failed, withdrawing optimism built on earlier-stage data for apazunersen (GTX-102). The company reported the Aspire study did not meet the primary endpoint tied to change from baseline in Bayley-4 cognitive raw score and also missed a key secondary endpoint in the Multidomain Responder Index. The decision marks a critical inflection point for Ultra-rare neurology development, where limited approved options heighten sensitivity to endpoint performance. Ultragenyx indicated it will evaluate “significant expense reductions” while weighing next steps for the program after the late-stage disappointment. For investors and researchers, the failure also re-energizes scrutiny of how trials in severe neurodevelopmental disorders select and sequence cognitive and functional endpoints, particularly for antisense mechanisms aimed at restoring aspects of cognition and communication. The company’s next moves will shape how similar Angelman and adjacent CNS RNA-targeted approaches calibrate development strategy.