Shares of Ultragenyx Pharmaceutical fell more than 40% in premarket trading on September 3, 2026, after the company disclosed that apazunersen (GTX-102), an investigational antisense oligonucleotide therapy for Angelman syndrome, failed to meet its primary and secondary endpoints in the phase 3 ASPIRE trial, according to a report from Reuters.¹ Ultragenyx reported the topline results on September 2, saying the therapy did not achieve the primary endpoint of change in Bayley-4 cognitive raw score, nor the key secondary endpoint of net response on the Multidomain Responder Index (MDRI), though its safety profile remained consistent with earlier phase 1/2 data.²
Key facts
- Drug: Apazunersen (GTX-102; Ultragenyx Pharmaceutical)
- Class: Antisense oligonucleotide (intrathecal administration)
- Indication studied: Angelman syndrome, pediatric patients
- Result: Failed primary (Bayley-4 cognitive score) and key secondary (MDRI) endpoints
- Safety: Consistent with phase 1/2 profile; no new signals reported
- Market reaction: Ultragenyx shares fell more than 40% in premarket trading
- Regulatory history: FDA breakthrough therapy, orphan drug, fast track designations
- Next steps: Ultragenyx evaluating program's future; deciding on expense reductions
"Based on everything we observed in the robust [p]hase 1/2 clinical development program and long-term extension study, we are disappointed by the Aspire result," said Emil Kakkis, MD, PhD, chief executive officer and president of Ultragenyx, in a company press release.² "Even more, we are disappointed for the global patient community who has invested so much in early-stage research, working to bring a first-ever treatment to their children."
What did the ASPIRE trial show?
ASPIRE compared apazunersen with placebo in children with Angelman syndrome. The randomized groups were comparable at baseline and consistent with the population studied in the earlier phase 2 trial. The company said there were no differences between the treated and control groups that could support efficacy, either in Bayley cognitive raw scores or in the MDRI's net response or the mean changes across its 5 individual endpoints.² Ultragenyx said it will evaluate the apazunersen program in light of the outcome and make a decision on its future. The company will also assess planned operations to implement expense reductions while supporting its commercial business.²
Why is a treatment for Angelman syndrome significant?
Angelman syndrome is a rare neurogenetic disorder caused by loss of function of the maternally inherited UBE3A gene, causing cognitive impairment, motor impairment, and debilitating seizures; most affected individuals cannot speak, and none can live independently.² There are currently no approved therapies for Angelman syndrome, which is estimated to affect approximately 60,000 people in commercially accessible geographies, according to the company.² Apazunersen is designed to target the UBE3A antisense transcript to reactivate expression of the paternal UBE3A allele, which is normally silenced in neurons.²
