Benzinga | Oct 4, 2021 07:09AM EDT

Xenon Pharmaceuticals Announces Topline Results From Phase 2b 'X-TOLE' Clinical Trial of XEN1101 For The Treatment Of Focal Epilepsy; Co. Reports 'All Primary and Secondary Seizure Reduction Endpoints Statistically Significant Across All Dose Groups'

Xenon Pharmaceuticals Inc. (NASDAQ:XENE), a neurology-focused biopharmaceutical company, today reported positive topline results from the Phase 2b X-TOLE clinical trial, which evaluated the clinical efficacy, safety, and tolerability of XEN1101 -- a differentiated Kv7 potassium channel modulator -- administered as adjunctive treatment in adult patients with focal epilepsy.

The trial met its primary efficacy endpoint with XEN1101 demonstrating a statistically significant and dose-dependent reduction from baseline in monthly (defined as 28 days) focal seizure frequency when compared to placebo (monotonic dose response; p<0.001). Additional primary and secondary measures included a pairwise comparison of each active dose to placebo and a responder analysis with the proportion of patients who achieved a 50% or greater reduction in monthly focal seizure frequency from baseline. These results are shown in the following table; all p-values are 2-sided comparing the active dose to placebo:

XEN1101 25 mg XEN1101 20 mg XEN1101 10mg Placebo

(N=112) (N=51) (N=46) (N=114)Median Reduction from Baseline 33.2% 52.8% 46.4%in Monthly Focal Seizure (p=0.035) 18.2 % (p<0.001) (p<0.001)Frequency Patients with at least a 50% 54.5% 43.1% 28.3%Reduction in Monthly Focal 14.9 % (p<0.001) (p<0.001) (p=0.037)Seizure Frequency from Baseline

Jacqueline A. French, MD, Professor in the Department of Neurology at NYU Langone Health and Co-director of Epilepsy Clinical Trials at NYU Langone's Comprehensive Epilepsy Center; Founder/Director of the Epilepsy Study Consortium; and Chair of the XEN1101 X-TOLE Steering Committee, stated, "Many patients today are living with the debilitating impacts of focal seizures, even while taking multiple anti-seizure medications, so there is a substantial need for new, efficacious and well-tolerated therapies. The X-TOLE results generated from this large, multicenter, controlled trial are truly exciting because they demonstrate impressive efficacy of XEN1101 for adult patients with focal epilepsy, including those with seizures that are deemed difficult to treat. In addition, physicians and patients could benefit from XEN1101's other important attributes, such as once-a-day dosing in the evening with no titration. With its unique potassium channel mechanism-of-action, the strength of these topline data suggest XEN1101 could play an important role in treating focal epilepsy."

Dr. Christopher Kenney, Xenon's Chief Medical Officer commented, "On behalf of the entire Xenon team, I wish to extend our thanks to the patients, investigators, and site coordinators who participated in the X-TOLE study. We have generated strong evidence that supports the efficacy, safety and tolerability of XEN1101 and depicts a highly favorable product profile for XEN1101. Importantly, we saw statistically significant reductions of focal onset seizures compared to placebo across all dose groups, which suggests it is highly active in the central nervous system. With these compelling topline results, we are eager to work with the FDA to plan for an expedited development path moving forward."

Designed as a randomized, double-blind, placebo-controlled, multicenter study, the Phase 2b X-TOLE clinical trial evaluated the clinical efficacy, safety, and tolerability of XEN1101 administered as once-daily adjunctive treatment in adult patients with focal epilepsy. The study included a total of 325 randomized and treated subjects in the safety population and 323 subjects in the modified intent to treat population for the efficacy analyses. Subjects had an average age of 40.8 ? 13.3 years, and 8.9%, 40.3%, or 50.8% of the subjects were on and continued taking one, two, or three stable background anti-seizure medications (ASMs) throughout the study, respectively, and failed a median of 6 previous ASMs prior to study entry. The median baseline seizure frequency across the study groups was approximately 13.5 per month. Of the 285 subjects who completed the double-blind period, 96.5% entered the open-label extension to evaluate the long-term safety, tolerability, and effectiveness of XEN1101.