Ultragenyx Apazunersen (GTX-102) Antisense Oligonucleotide Fails Phase 3 Aspire Study in Angelman Syndrome; Misses Primary Bayley-4 Cognitive Endpoint
Ultragenyx Pharmaceutical (NASDAQ: RARE) announced Wednesday September 2, 2026 that the Phase 3 Aspire study of apazunersen (GTX-102, an intrathecally-administered antisense oligonucleotide designed to reduce production of the paternal UBE3A antisense transcript in Angelman syndrome) did not meet its primary endpoint of change from Baseline in Bayley-4 cognitive raw score, nor its key secondary endpoint of Multidomain Responder Index (MDRI) net response. The 129-patient trial enrolled ages 4 to 17 with genetically confirmed full maternal UBE3A gene deletion. Safety was consistent with the Phase 1/2 program. The result is the first Phase 3 miss for an antisense drug in Angelman syndrome and closes off the primary regulatory path for GTX-102 in the enrolled population. Ultragenyx will discuss next steps with regulators and continues the Aurora study evaluating GTX-102 in additional Angelman syndrome genotypes and age groups. RARE shares fell substantially in premarket trading. The failure joins Roche/Ionis's tominersen Huntington's disease miss (GENERATION HD1, 2022) and Sage-Biogen's zuranolone MDD approval-with-restrictions as instances where CNS antisense programs failed to translate promising Phase 1/2 signals into Phase 3 wins.