First patient dosed in pivotal phase III Aspire study evaluating GTX 102 in Angelman syndrome- Ultragenyx Pharmaceutical

The global Phase III Aspire study will enroll approximately 120 children ages 4 to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Participants will be randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group during the 48-week primary efficacy analysis period. Participants in the active treatment group will receive three, monthly 8 mg loading doses of GTX-102 followed by dosing in a maintenance period that will increase to a maximum dose of 14 mg of GTX-102 quarterly. Patients in the sham comparator group will be eligible to crossover onto treatment after Week 48 is complete. 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.

At the 2024 Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit in November, the company presented data from the Phase I/II study that confirmed the Phase III Aspire study dosing strategy and that the study is amply powered to establish the efficacy of GTX 102 on the primary endpoint of change in cognition, as measured by Bayley-4, or the key secondary endpoint of MDRI at the Week 48 timepoint.

"Initiation of patient dosing in our Phase III  Aspire study represents an important step forward in the development of an effective, and much needed, treatment for patients and families affected by Angelman syndrome,” said Dr. Eric Crombez, chief medical officer at Ultragenyx. "Our goal with Aspire is to confirm the safety and clinical efficacy of GTX102 in a large, randomized trial with a population that represents the majority of patients with Angelman syndrome. Additionally, the Aurora study will further assess safety and validate efficacy in patients with different genotypes and in younger and older patients."

“Angelman syndrome affects cognitive and motor function, making walking, communicating, and performing many everyday tasks more difficult for individuals living with Angelman syndrome. As a united community, ASF and FAST work together to further awareness and treatment of Angelman syndrome and are excited by all the recent progress in research and drug development. The initiation of the Phase III Aspire study by Ultragenyx is a significant achievement and something the community should celebrate,” stated Amanda Moore, chief executive officer at the Angelman Syndrome Foundation (ASF) and Ryan Fischer, chief operating officer at Foundation for Angelman Syndrome Therapeutics (FAST), in a joint statement.