‘Urgent need’ for treatment drives GTX-102 study enrollment
Angelman study achieved full enrollment in about seven months
The Phase 3 clinical trial that’s testing an experimental therapy for Angelman syndrome has finished enrolling patients.
The Aspire study (NCT06617429), whose results are expected in late 2026, achieved full enrollment, with about 129 participants, barely half a year after it began enrolling last December, according to Ultragenyx Pharmaceutical, which is developing GTX-102 (apazunersen) and sponsoring its trial.
“The accelerated enrollment of the Phase 3 Aspire study underscores the urgent need and strong desire for an effective treatment for these patients,” Eric Crombez, MD, chief medical officer at Ultragenyx, said in a company press release. “Support from the Angelman syndrome community was critical to the achievement of this important milestone for GTX-102 with completion of enrollment in seven months. We are grateful to the study site teams, investigators, and families for their dedication and support.”
Angelman syndrome is caused by mutations in the UBE3A gene. Everyone inherits two copies of the gene, one from each parent, but in nerve cells, the copy inherited from the father is usually inactive. People with Angelman syndrome have a missing or faulty copy of the gene inherited from the mother and, since the other one is normally inactive, they’re left with no functional UBE3A gene in their nerve cells.
What is GTX-102?
GTX-102 is an antisense oligonucleotide that contains a short piece of genetic material that’s designed to inhibit a mechanism that normally silences the paternal UBE3A gene copy. In other words, the therapy is intended to turn on the healthy version of UBE3A from the father so it can compensate for the dysfunctional maternal gene. GTX-102 is given by intrathecal injection, that is, into the spinal canal.
“To have a treatment in development with the potential to correct the underlying genetic error that forms the basis of Angelman syndrome, restore protein function, and recover function for patients is extremely meaningful,” said Jean-Baptiste Le Pichon, MD, PhD, investigator on the Aspire trial at Children’s Mercy.
In Aspire, participants will be randomly assigned to receive GTX-102 injections or sham injections for about a year. These will be given every month for the first three injections and every three months thereafter. The main goal is to assess the impact of treatment on Bayley-4 Cognitive Raw Score, a standardized measure of cognition. Other measures also will be assessed, including tests of motor function and behavior, along with safety outcomes.
Aspire enrolled patients, ages 4-17 whose maternal UBE3A copy is entirely missing. Ultragenyx is working to launch a separate study dubbed Aurora to test the therapy in other ages and mutation types. Aurora should launch later this year, according to Ultragenyx.
Both studies build on data from KIK-AS (NCT04259281), a Phase 1/2 study whose findings indicated GTX-102 was generally well tolerated. No serious side effects were reported and the therapy led to improvements in cognition.
“The continued developmental gains observed in the Phase 1/2 study provide a strong foundation as we advance this program with the potential to address the underlying genetic cause of this disease and enhance the quality of life for children living with Angelman syndrome,” Crombez said.
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