First patient administered gene therapy trial of GTX-102 in Phase 3 Aspire stage

Ultragenyx Pharmaceutical has initiated a Phase 3 trial for its experimental gene therapy, GTX-102, in the treatment of Angelman syndrome. The global Aspire study (NCT06617429) aims to enroll about 120 children and adolescents, ages 4 to 17, with Angelman syndrome caused by a complete loss of the maternal UBE3A gene.

The Aspire trial, scheduled to complete in 2027, is a pivotal study, meaning that positive results could serve as the foundation for regulatory applications seeking GTX-102's approval. Participants in the active treatment group will receive three initial monthly 8 mg doses of GTX-102, followed by a maintenance period with a gradually increasing dosage up to a maximum of 14 mg administered every three months. The control group will receive a placebo.

The main goal of the Aspire trial is to assess improvements in cognition using the Bayley-4 Cognition Raw Score. Secondary measures include the Multi-domain Responder Index to evaluate cognition, receptive communication, behavior, motor function, and sleep.

Recruitment for the Aspire study is happening at sites in the U.S., with several other sites planning to open in the U.S., Canada, Australia, Japan, and some European countries. Ultragenyx also plans to launch another trial, Aurora, later this year to assess the treatment's efficacy in patients from other age groups and with different genotypes.

Angelman syndrome is a rare genetic disorder caused by a mutated or missing UBE3A gene copy inherited from the mother. Symptoms include developmental delay, motor and communication impairments, behavioral issues, and disturbed sleep.

GTX-102 is an antisense oligonucleotide designed to inhibit a molecule called UBE3A antisense transcript, preventing silencing of the paternal copy of the UBE3A gene. The treatment is given through direct injection into the spinal canal.

The Phase 1/2 KIK-AS trial demonstrated the treatment had an acceptable safety profile, with no serious adverse events. In the active treatment group of the trial, participants with a missing maternal UBE3A gene copy experienced clinically significant improvement in cognition, communication, motor function, sleep, and behavior.

The Angelman Syndrome Foundation (ASF) and the Foundation for Angelman Syndrome Therapeutics (FAST) have expressed excitement about the progress in research and drug development for Angelman syndrome. The Aspire trial's results will be used as the foundation for regulatory applications seeking GTX-102's approval.

Each individual inherits two copies of every gene, one from each biological parent. In neurons within the central nervous system, the UBE3A gene copy inherited from the father is usually inactive. In individuals with Angelman syndrome, the missing maternal UBE3A gene copy leads to a lack of UBE3A protein, causing the symptoms associated with the disorder.

The Aspire trial is a significant step forward in the development of a potential treatment for Angelman syndrome. The results from the Aspire trial could provide hope for families affected by this rare genetic disorder.

First patient administered gene therapy trial of GTX-102 in Phase 3 Aspire stage