Ultragenyx Pharmaceutical Inc. has announced positive Phase 1/2 data supporting the Phase 3 Aspire study of GTX-102, an investigational antisense oligonucleotide for Angelman syndrome. The data, presented at a recent medical conference, demonstrated sustained improvements across multiple domains in patients with Angelman syndrome and confirmed that the Phase 3 Aspire study is sufficiently powered to establish the efficacy of GTX-102.
As of the September data cut-off, patients (n=40) in the Dose-escalation and Expansion Cohorts at Week 48 (Day 338) demonstrated a mean change in Bayley-4 Cognition Growth Scale Value (GSV) score from baseline of +6.7, compared to the minimally important difference of +5. Using the Phase 3 primary endpoint of Bayley-4 Cognition Raw score, the mean change from baseline was +10.9. Ultragenyx noted that the data suggest the Phase 3 study has greater than 95% power to detect a treatment effect, even if the response in the sham arm is up to three times higher than observed changes in available natural history data.
Clinically Meaningful Improvements
Week 48 (Day 338) data from 28 patients in Expansion Cohorts A&B were evaluated with the Phase 3 key secondary endpoint of MDRI and showed a total net response of +2.0. The data demonstrate that approximately 80% (22 of 28 patients) of patients have achieved clinically meaningful net improvement in at least one domain.
Safety Profile
According to Ultragenyx, GTX-102 demonstrated a consistent and acceptable safety profile as of the data cutoff, suggesting that the drug is well-tolerated in this patient population.
Implications for Phase 3 Aspire Study
The data confirm that the Phase 3 Aspire study is amply powered to establish the efficacy of GTX-102 on the primary endpoint of cognition or the key secondary endpoint of MDRI at the Week 48 timepoint.
