Ultragenyx disclosed that its Phase 3 Angelman syndrome trial Aspire, evaluating apazunersen (GTX-102), missed both key goals, reigniting debate about how to develop and sequence next-generation therapies for a disease still lacking approved options. The company reported failure to achieve the primary endpoint on Bayley-4 Cognitive raw score change from baseline and to hit a key secondary endpoint in the Multidomain Responder Index. The outcome is expected to trigger cost and program review decisions as investors reassess the mechanism and endpoint strategy for RNA-targeted approaches in Angelman. Industry observers also noted the readthrough implications for other late-stage or platform-adjacent programs targeting related pathways. Even with the mechanistic uncertainty that often follows negative Phase 3 results, the failure increases scrutiny on endpoint selection and patient stratification in rare neurodevelopmental drug development.