The GTX-102 device demonstrates consistent safety during a year-long trial in the Angelman study

The clinical study, KIK-AS (NCT04259281), evaluating the safety and tolerability of the gene therapy GTX-102, developed by Ultragenyx Pharmaceutical, has resumed following a pause late in 2020. The study aims to treat Angelman syndrome, a genetic disorder characterised by intellectual disability, speech impairment, and seizures.

The study was halted due to five patients experiencing serious yet reversible leg weakness after receiving high doses of GTX-102. In response, the study's protocol was revised to address safety concerns, with changes including narrowing the dose range and altering the mode of administration. The FDA agreed to allow higher trial dosing in May, following similar decisions in the U.K., Canada, and Australia.

GTX-102 is an antisense oligonucleotide designed to reactivate the father's UBE3A gene copy, which provides instructions to make an enzyme that sends unwanted or faulty proteins off for recycling within cells to keep them healthy. The therapy pairs with a naturally occurring antisense oligonucleotide in brain cells, UBE3A-AS, to restore UBE3A levels.

The study's resumption marks a significant step forward, as Ultragenyx Pharmaceutical plans to conduct a Phase 3 study of GTX-102 starting in 2022. The company has already dosed the first patient in this pivotal trial. The study will now test a similar dose range, and it is continuing to enroll eligible patients, ages 4 to 17.

New trial sites have opened in the past two months at locations worldwide, including one in the U.S. and several in European countries. Interim data from 11 patients followed for six months showed early evidence of improvement with GTX-102 in areas such as communication, behaviour, sleep, and motor skills.

No serious side effects or reports of leg weakness were found among children and adolescents with at least one year of follow-up. Ultragenyx plans to share data covering at least six months of treatment in 20 or more expansion phase patients early next year.

The resumption of the study is a testament to the commitment to patient safety and the potential of GTX-102 as a treatment for Angelman syndrome. As the study progresses, we look forward to further updates on its safety and efficacy.

The GTX-102 device demonstrates consistent safety during a year-long trial in the Angelman study