Ultragenyx said its Phase 3 trial of GTX-102 for Angelman syndrome failed to show benefit versus sham treatment. The setback follows earlier excitement from the program’s early results and raises new questions about whether the antisense oligonucleotide approach can meet clinical endpoints in a larger, late-stage population. The failure is also financially consequential. With much of Ultragenyx’s approved portfolio focused on ultra-rare indications, investors had leaned on Angelman as a potential pathway to sustained growth. Ultragenyx now faces the typical post-Phase 3 decision cycle—whether to pursue alternative endpoints, patient subgroups, or next-generation molecules—while recalibrating near-term capital allocation.