Ultragenyx’s Angelman Phase 3 Miss Triggers Review and Cost-Cutting

Ultragenyx said its Phase 3 Aspire trial of apazunersen (GTX-102) in Angelman syndrome failed both its primary endpoint—change from baseline in Bayley-4 cognitive raw score—and the key secondary Multidomain Responder Index endpoint. The company reported no efficacy difference versus the sham-control group.

The randomized study enrolled 129 patients with a full maternal UBE3A gene deletion. Safety findings were consistent with the earlier Phase 1/2 program, but the efficacy result leaves the future of apazunersen under review.

Ultragenyx said it will assess its operating plans and implement “significant expense reductions,” without yet detailing the size or timing. It previously reduced roughly 10% of its workforce after separate late-stage setbacks in osteogenesis imperfecta.

The news was a substantial market setback:
Reuters reported that shares fell more than 40% in premarket trading, while Fierce Biotech reported a 43% after-hours drop. Analysts characterized the result as a major hit to a key growth prospect.

Management said it will continue supporting its commercial rare-disease business and remains focused on reaching profitability in 2027. The outcome also underscores the lack of approved disease-modifying therapies for Angelman syndrome.