Results of KIK-AS Angelman gene therapy study due 1st half of year

Findings should aid in design of Phase 3 study toward GTX-102's approval

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The Phase 1/2 KIK-AS clinical trial, which is testing the experimental genetic therapy GTX-102 in children with Angelman syndrome, has finished enrolling patients.

With 74 enrolled, including 53 in dose-expansion groups, the therapy’s developer Ultragenyx Pharmaceutical said results will be available in the next few months.

“With completion of enrollment in the Phase 1/2 trial, we remain on track to report results in the first half of 2024 from at least 20 expansion cohort patients on therapy for a minimum of [six] months,” Eric Crombez, MD, Ultragenyx’s chief medical officer, said in a company press release.

The findings are expected to inform the design of a future Phase 3 trial, including determining GTX-102’s best dosage and figuring out the optimal trial endpoints to test if it’s working. Phase 3 studies are large clinical trials designed to test a therapy’s efficacy. Positive results can typically support applications to approve new therapies.

“We are confident that the cumulative safety and efficacy data will allow for dose and endpoint selection to support our Phase 3 program,” Crombez said.

Angelman syndrome is caused by a mutation in the maternal copy of the gene UBE3A. Everyone inherits two copies of the gene, one from each parent, but usually only the maternal copy is active.

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What is GTX-102?

GTX-102 contains a type of genetic medication called an antisense oligonucleotide that inhibits the molecule that keeps the paternal copy of UBE3A from being active in cells. This molecule is called UBE3A antisense transcript (UBE3A-AS).

By turning on the paternal gene, the therapy aims to enable a functional UBE3A protein to be produced, which should ease disease symptoms.

The KIK-AS trial (NCT04259281) is testing multiple doses of GTX-102, administered via intrathecal injection, that is, through the spinal cord.

The study was suspended in 2020 after some patients given high doses developed leg weakness, but it was cleared to restart about a year later following changes to the trial’s protocol, including narrowing the dose range and requiring intrathecal injection.

Last year, regulatory agencies cleared the trial to test higher doses, and interim data suggested no new serious safety issues and hinted that the therapy may be providing patients with a clinical benefit over what would be expected in untreated Angelman syndrome.

These promising data recently led to GTX-102’s designation as a Priority Medicine (PRIME) from the European Medicines Agency (EMA). The EMA grants PRIME designation to support developers of promising medicines that show significant therapeutic advantages over existing treatments or provide benefits to patients with limited treatment options.

“We appreciate the support of the Angelman community, including the patients, families and healthcare providers, as we urgently work together to develop a new treatment option that may be able to improve the quality of life of those impacted by this devastating disease,” Crombez said.