GTX-102 data show continued developmental gains in Angelman
Children in extension study showed gains across multiple domains
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Long-term data from a clinical study suggest that the experimental treatment GTX-102 (apazunersen) is associated with continued improvements and developmental gains in children with Angelman syndrome, with results from a Phase 3 trial testing the therapy expected later this year, according to an update from developer Ultragenyx Pharmaceutical.
“The latest long-term GTX-102 Phase 1/2 data further support the potential of the program, as it heads toward Phase 3 results later this year,” Emil D. Kakkis, MD, PhD, CEO and president of Ultragenyx, said in a company press release.
Angelman syndrome is a genetic disorder caused by problems with a gene called UBE3A. Everyone inherits two copies of the gene, one from each biological parent, but in certain brain cells, the copy inherited from the biological father is normally inactive. Angelman occurs when the copy inherited from the biological mother is missing or mutated, meaning brain cells are left without a working, active version of the gene.
GTX-102 aims to restore UBE3A activity
GTX-102 is an RNA-based therapy designed to reactivate the copy of UBE3A inherited from the biological father, restoring the gene’s activity in cells that lack a functional maternal copy. The therapy is given by injection into the spinal canal, known as an intrathecal injection.
The Phase 1/2 KIK-AS clinical trial (NCT04259281) tested various doses of GTX-102 in children with Angelman syndrome. Earlier data suggested the therapy was generally well tolerated and may improve cognition and other developmental areas.
Of the 74 young people treated with GTX-102 in KIK-AS, 66 are continuing to receive treatment as part of an ongoing long-term extension. These patients have now been on continuous GTX-102 treatment for more than three years on average, with some individuals in their fifth year of treatment. Most patients are specifically receiving GTX-102 at a dose of 14 mg every three months.
According to Ultragenyx, patients on long-term GTX-102 “have continued to show positive improvements across multiple domains and continued to gain ground developmentally.” The company also said the therapy has shown a consistent safety profile with long-term treatment, with no new cases of temporary leg weakness and no other recurring drug-related serious adverse events. The company did not provide further details, noting that in-depth results will be presented at a future scientific conference.
Ultragenyx is running two ongoing clinical trials to further test the safety and efficacy of GTX-102. The Phase 3 Aspire (NCT06617429) trial enrolled 129 children with Angelman syndrome caused by a full deletion of the maternal UBE3A gene copy. Participants were randomly assigned to receive GTX-102 or a sham comparator for about a year, with the main goal of assessing the treatment’s effect on a standard cognitive measure, the Bayley-4 Cognitive Raw Score. The Aspire study is on track to have results later this year.
The Phase 2/3 study Aurora (NCT07157254), meanwhile, is testing GTX-102 in patients with a wider range of ages and mutation types. That study is still recruiting participants at sites in the U.S., Europe, and South America. Ultragenyx said it expects to finish enrollment later this year.
