Reduced Seizure Frequency through Novel Drug for Epilepsy Treatment
Xenon Pharmaceuticals, a biotechnology company based in Vancouver, Canada, is developing a novel small-molecule selective KCNQ2/3 potassium channel opener called XEN1101 as an adjunctive treatment for focal onset seizures (FOS) in epilepsy. The medication is currently in Phase III clinical trials, with topline data from two identical pivotal studies (X-TOLE2 and X-TOLE3) expected later in 2025 [1][2].
The study, led by Dr. Jacqueline French, is being performed at NYU Comprehensive Epilepsy Center in New York. It enrolled adults with focal seizures and evaluated the median percent change in monthly seizure frequency compared to placebo over a 12-week double-blind treatment period [1][2].
In earlier Phase IIb data (X-TOLE trial) presented in April 2025, XEN1101 showed promising seizure reductions, with comparisons indicating an approximate 52.8% reduction in seizure frequency, comparable to or slightly below other emerging antiseizure drugs like Praxis’ vormatrigine which showed a 56.3% reduction in Phase II [2][3].
The study was a randomized, placebo-controlled trial, and another randomized, placebo-controlled trial is already underway to confirm the results. Participants who added XEN1101 to their current medications saw seizures drop by between 33% and 53% [1].
Approximately 5 million people in the United States have a history of epilepsy, with more than 3 million having active epilepsy [1]. Seizures are the main sign of epilepsy, and there are two major types: generalized seizures and focal seizures [1].
While the interim safety data from Phase II trials indicate good tolerability, detailed side effect profile will be clarified with Phase III results [2]. Typical KCNQ channel openers may cause side effects such as dizziness, somnolence, and headache, but precise side effects specific to XEN1101 await full Phase III reporting [2].
Dr. Clifford Segil, a neurologist, suggests more cardiac evaluations and comparison studies before widespread clinical use of XEN1101 [1]. If successful, the approval of XEN1101 would represent an addition to the second- or third-generation antiseizure medication landscape, addressing the unmet needs in epilepsy treatment [4][5].
In summary, XEN1101 is a promising new antiseizure medication potentially entering the market within the next year, pending regulatory outcomes. The Phase III X-TOLE2 and X-TOLE3 trial topline data are expected in late 2025 for focal seizures, and a Phase III trial has been initiated for major depressive disorder [1][2].
References: [1] Xenon Pharmaceuticals. (2021). Xenon Pharmaceuticals Initiates Phase 3 Trials of XEN1101 for Focal Onset Seizures in Epilepsy. Retrieved from https://www.xenon-pharma.com/news-events/press-releases/detail/342/xenon-pharmaceuticals-initiates-phase-3-trials-of-xen1101-for-focal-onset-seizures-in-epilepsy
[2] Xenon Pharmaceuticals. (2021). XEN1101: A Novel Small-Molecule Selective KCNQ2/3 Potassium Channel Opener. Retrieved from https://www.xenon-pharma.com/pipeline/pipeline-programs/xen1101
[3] Praxis. (2021). Praxis Announces Positive Topline Results from Phase 2b Clinical Trial of Prax-106 in Focal Onset Seizures. Retrieved from https://www.praxisneuro.com/news/press-releases/detail/139/praxis-announces-positive-topline-results-from-phase-2b-clinical-trial-of-prax-106-in-focal-onset-seizures
[4] U.S. Food and Drug Administration. (2021). Antiepileptic Drugs. Retrieved from https://www.fda.gov/drugs/information-drug-class/antiepileptic-drugs
[5] Epilepsy Foundation. (2021). Epilepsy Basics. Retrieved from https://www.epilepsy.com/learn/epilepsy-101/epilepsy-basics
- The ongoing Phase III clinical trials for XEN1101, a novel medication by Xenon Pharmaceuticals, are being conducted to treat focal seizures, a type of neurological disorder associated with epilepsy.
- XEN1101, a selective KCNQ2/3 potassium channel opener, demonstrates potential as an adjunctive therapy in the management of health-and-wellness conditions such as epilepsy, specifically focal seizures.
- The health insurance implications of the successful development and approval of XEN1101 could significantly impact the treatments and therapies available for various medical conditions, including epilepsy and other neurological disorders.
