Mechanism and Promise Behind XEN1101 in Focal Epilepsy: Jacqueline French, MD

WATCH TIME: 3 minutes

"Retigabine was initially hailed as a breakthrough, but due to its short half-life and the rare side effect of blue discoloration, it was eventually withdrawn. However, the success of potassium channel opening was clear, and XEN-1101 is now proving to be an exciting, more effective, and safer alternative."

Focal seizures represent the most common seizure type and focal epilepsies the most common epilepsy type. There are currently 17 drugs approved for the treatment of focal seizures, with cenobamate (Xcopri; SK Life Science) as the very latest option. Despite the plethora of available therapies, some patients continue to struggle with their seizure control.

One investigational drug, Xenon’s XEN1101, is being evaluated as a treatment for adults with focal epilepsy in 2 major phase 3 trials, dubbed X-TOLE2 (NCT05614063) and X-TOLE3 (NCT05716100). The studies, both randomized, double-blind, placebo-controlled trials. Assess the efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in adults with focal seizures who are taking 1 to 3 antiseizure medications. Similar in design, the studies include a 12-week double-blind period, with an 8-week follow-up, and an optional open-label extension.

XEN1101 is built to selectively potentiate the open state of KCNQ2/3 channels, through subtypes Kv7.2 to Kv7.5, which reduces the onset of rapid action potential spiking in neurons. In a recent interview with NeurologyLive®, Jacqueline A. French, MD, primary investigator of the X-TOLE studies, discussed the mechanism of action behind the agent, noting that it compliments traditional sodium channel inhibitors. She provided a history of this approach in treating epilepsy, and how XEN1101 may be better than previous potassium channel modulators like retigabine, which was withdrawn due to adverse effects. Furthermore, French, a professor of neurology at NYU Grossman School of Medicine, highlighted the potential of XEN1101 based on its strong efficacy in early trials, positioning itself as a potential new option for patients with focal epilepsy.