Ultragenyx Presents Positive Update on GTX-102 Angelman Syndrome Program at FAST’s 17th Annual Global Science Summit

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Ultragenyx Pharmaceutical Inc.
Ultragenyx Pharmaceutical Inc.

Phase 1/2 data show improvements across all domains and confirm that Phase 3 Aspire study is amply powered to establish efficacy of GTX-102

Phase 3 program on track to begin enrollment by end-of-year

NOVATO, Calif., Nov. 09, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced Phase 1/2 data in support of the Phase 3 Aspire study for GTX-102, its investigational antisense oligonucleotide for Angelman syndrome, that will be presented at the 2024 Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit in Orlando, Florida.

“Cognition is the building block for the development and ascertainment of many new skills across a range of the domains we have evaluated in the Phase 1/2 study. The data presented at FAST reinforce that the Aspire Phase 3 primary endpoint of cognition, as measured by Bayley-4, appears very well powered to show statistically significant separation between the GTX-102 and sham arms,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We are on track to begin enrolling the Phase 3 Aspire study by the end of this year and have a robust and experienced global network of sites that will enable accelerated study execution.”

The global Phase 3 Aspire study will enroll approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion and will include a 48-week primary efficacy analysis period. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint will be the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep.

As of the September Phase 1/2 data cut-off, patients in the Dose Expansion Cohorts demonstrated continued improvement across multiple domains at Week 48 (Day 338). Patients (n=40) in the Dose-escalation and Expansion Cohorts at Week 48 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. This suggests 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 data1.

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 (p-value < 0.0001). The data demonstrate that approximately 80% (22 of 28 patients) of patients have achieved clinically meaningful net improvement in at least one domain.

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