Enhanced Cognitive Functioning in Children and Adolescents with Angelman Syndrome Potentially Aided by GTX-102 Technology

In a significant development for the treatment of Angelman syndrome, Ultragenyx Pharmaceutical Inc.'s investigational gene therapy, GTX-102, has shown promising results in a Phase 1/2 trial. The new data was presented at the 2024 Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit last month in Orlando, Florida.

GTX-102 is an antisense oligonucleotide designed to reactivate the paternal UBE3A gene copy, which is often absent or malfunctioning in patients with Angelman syndrome. The disease develops when the copy inherited from the mother is mutated or missing.

In the Phase 1/2 trial, most patients saw clinically meaningful improvements in communication, motor function, sleep, and behavior. Using Aspire's primary measure of cognition, the Bayley-4 Cognition Raw score, the improvement was 10.9 points. After a year of treatment, patients treated with GTX-102 had a mean increase of 6.7 points in their Bayley-4 Cognition Growth Scale Value (GSV) scores.

The Phase 3 Aspire trial (NCT06617429), designed to assess GTX-102's efficacy, is expected to enroll 120 patients, ages 4-17, with a full maternal deletion of the UBE3A gene and who can walk independently or with an assistive device. The trial's main goal is to assess the safety and tolerability of multiple ascending doses of GTX-102.

Eric Crombez, MD, chief medical officer at Ultragenyx, stated that they are on track to begin enrolling the Phase 3 Aspire study by the end of this year. The study is expected to be completed in 2027.

It's worth noting that the data from 28 patients showed a significant response of 2 points on the Multi-domain Responder Index (MDRI), indicating about 80% of patients achieved clinically meaningful improvements in at least one MDRI domain.

The KIK-AS trial (NCT04259281), another study by Ultragenyx, is assessing the safety and tolerability of multiple doses of GTX-102 in 74 children and adolescents, ages 4-17. This trial enrolled patients with missing maternal UBE3A gene, associated with more severe forms of Angelman.

Ultragenyx has a robust and experienced global network of sites for accelerated study execution, which should aid in the swift progress of these trials. The data supports the starting of the pivotal Phase 3 Aspire trial, offering hope for those affected by Angelman syndrome.

Enhanced Cognitive Functioning in Children and Adolescents with Angelman Syndrome Potentially Aided by GTX-102 Technology