FDA permits Ultragenyx to escalate GTX-102 doses in KIK-AS trial experiments

In a significant breakthrough for the treatment of Angelman syndrome, Ultragenyx Pharmaceutical has received approval from the U.S. Food and Drug Administration (FDA) to increase the dosing of its gene therapy, GTX-102, in children and adolescents with the condition.

Scott Stromatt, MD, the chief medical officer of neurology clinical development at Ultragenyx, expressed his eagerness about the development. As of May 4, 13 patients have been dosed for more than a year, with the longest dosing reaching over 18 months (one and a half years).

Interim data from the ongoing Phase 1/2 clinical trial suggests that GTX-102 has shown improvements in sleep, communication, motor skills, and lessened disease severity. The study's primary goal is to assess the safety and tolerability of GTX-102, with secondary goals including assessing the therapy's pharmacokinetics.

GTX-102 is an antisense oligonucleotide that targets UBE3A-AS, a molecule that, in Angelman syndrome patients, lacks functional UBE3A. Normally, UBE3A-AS binds to the paternal copy of UBE3A in brain cells and inactivates it. GTX-102 is believed to reactivate the paternal copy of UBE3A in the brain to compensate for the lack of a working maternal copy of the gene.

Recruitment for the higher dose groups is currently underway across all clinical sites in the U.K., Canada, and Australia. The amendment to the KIK-AS trial protocol allows for testing of a similar dose range in all locations, including the U.S. Ultragenyx is working urgently to activate multiple study sites in the U.S. and plans to begin enrollment as quickly as possible.

The KIK-AS trial began dosing in 2021 and seeks to enroll approximately 40 participants to the expansion groups. The data from the trial will inform the treatment regimen for Phase 3 testing. Ultragenyx acquired GeneTx Biotherapeutics, and it is now developing GTX-102.

The data from the KIK-AS trial demonstrates important clinical activity across multiple functional domains impacted by Angelman syndrome with an acceptable safety profile. This development offers hope for families affected by Angelman syndrome, a condition characterised by developmental delays, speech impairments, movement disorders, and seizures.