XEN1101 significantly reduced monthly seizures for adults with focal-onset epilepsy
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Key takeaways:
- XEN1101 is a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener.
- A 25 mg dose of XEN1101 reduced monthly seizure frequency by 52.8%.
In adults with epilepsy, treatment with a novel, oral adjunctive therapeutic significantly reduced monthly occurrence of focal-onset seizures across three doses compared with placebo, according to research in JAMA Neurology.
“The Kv7.2/Kv7.3 voltage-gated potassium channels, which exhibit perisomatic and axonal expression in brain neurons, represent a particularly attractive target,” Jacqueline A. French, MD, a professor of neurology at the Comprehensive Epilepsy Center at NYU Langone School of Medicine, and colleagues wrote.
French and colleagues sought to evaluate the safety and efficacy of XEN1101 (Xenon Pharmaceuticals), a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener to treat focal-onset seizures (FOSs) as an adjunctive treatment.
Their phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted at 97 sites across Europe and North America from Jan. 30, 2019, to Sept. 2, 2021, and included a 6-week safety follow-up. A total of 325 individuals (mean age 40.8 years; 51.7% female; 91.7% white) who experienced four or more monthly FOSs while receiving stable treatment (1 to 3 ASMs) were randomized 2:1:1:2 without dosage titration to receive either 10 mg, 20 mg or 25 mg oral capsule XEN1101, or placebo, once per day with their evening meal for 8 weeks. On completion of the double-blind phase, patients were eligible to continue in an open-label extension. Those who did not choose continuance in the OLE had follow-up safety visits at 1 and 6 weeks after final dose.
The primary efficacy end point was median percent change from baseline in monthly FOS frequency. Treatment-emergent adverse events (TEAEs) were logged and comprehensive laboratory assessments were made. Modified intention-to-treat analysis was conducted in the 285 participants who completed the entire 8-week double-blind phase.
Results showed that treatment was associated with significant seizure reduction across all three doses. Median reduction from baseline in monthly FOS frequency was 52.8% (P<.001 vs. placebo; IQR, 80.4% to 16.9%) for 25 mg, 46.4% (P<.001 vs. placebo; IQR, 76.7% to 14%) for 20 mg, and 33.2% (P=.04 vs. placebo; IQR, 61.8% to 0%) for 10 mg, compared with 18.2% (IQR, 37.3% to 7%) for placebo.
XEN1101 was also generally well-tolerated and TEAEs were similar to those of commonly prescribed medications, with no deaths reported.
“The findings of this study suggest that XEN1101 has the potential to address the unmet need for a treatment with a novel mechanism of action for patients with [focal-onset seizures],” French and colleagues wrote.