Treatment resistant epilepsy : New drug shows promise

Many individuals with focal epilepsy continue to experience seizures even with the use of currently available antiseizure medications (ASMs). However, a new treatment approach has shown great potential in addressing this issue. XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, was evaluated in a phase 2b clinical trial for its efficacy and safety in the treatment of focal-onset seizures (FOSs).

The study, which took place over an 8-week treatment period, investigated XEN1101 from January 30, 2019, to September 2, 2021. The trial was conducted as a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging adjunctive study, involving adults who were experiencing four or more monthly FOSs despite receiving stable treatment with 1-3 ASMs. The research was conducted at 97 sites in North America and Europe.

Patients were randomly assigned to one of four groups: XEN1101 at doses of 25 mg, 20 mg, or 10 mg, or a placebo, which they took with food once daily for 8 weeks. Notably, XEN1101 demonstrated a robust dose-response relationship in reducing seizures. The median percent reduction from baseline in monthly focal-onset seizures (FOS) frequency was 52.8% for 25 mg, 46.4% for 20 mg, and 33.2% for 10 mg, compared to 18.2% for the placebo group. These results were statistically significant.

Importantly, XEN1101 was found to be generally well-tolerated, with Treatment-emergent adverse events comparable to those of commonly prescribed ASMs, and no Treatment-emergent adverse events leading to death were reported during the trial.

Ref:French JA, Porter RJ, Perucca E, et al. Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial. JAMA Neurol. Published online October 09, 2023. doi:10.1001/jamaneurol.2023.3542