Interim Long-term Safety and Efficacy of XEN1101, a Potent, Selective Potassium Channel Opener: Update from an Ongoing Open-label Extension of a Phase 2b Study (X-TOLE) in Adults with Focal Epilepsy
Jacqueline French1, Roger Porter2, Emilio Perucca3, Martin Brodie4, Michael Rogawski5, Cynthia Harden6, Jenny Qian6, Constanza Luzon Rosenblut6, Christopher Kenney6, Gregory Beatch6
1New York University Grossman School of Medicine and NYU Langone Health, 2University of Pennsylvania, 3Monash University, Melbourne, VI, Australia, and University of Melbourne (Austin Health), 4University of Glasgow Department of Medicine and Therapeutics, Western Infirmary, 5School of Medicine, University of California, Davis, 6Xenon Pharmaceuticals Inc.
Objective:
To report interim 18-month data from an ongoing, long-term, open-label extension (OLE) of a Phase 2b study (X-TOLE) of XEN1101 in adults with focal onset seizures (FOS).
Background:
In the double-blind period (DBP) of X-TOLE, XEN1101 (10, 20, and 25 mg QD with food) showed a dose-dependent, statistically significant, and rapid-onset reduction in seizure frequency. We report interim 18-month OLE safety and efficacy data.
Design/Methods:
Eligible patients enrolled in the 5-year OLE at 20 mg QD with food. Assessments occurred at week 3 in the OLE and at 3-month intervals thereafter. Safety assessments included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Primary efficacy outcome was median percentage change (MPC) in monthly (28-day) FOS frequency from DBP baseline.
Results:
285 patients completed the DBP and 275 (96.5%) enrolled in the OLE. At the 18-month OLE interim analysis (April 12, 2023), 182 had been treated for ≥1 year and 170 for ≥18 months; 159 (57.8%) patients continued participation. The majority of TEAEs were mild or moderate. The most common TEAEs were dizziness, coronavirus infection, headache, fall, and somnolence. 20.7% reported TEAEs leading to dose reduction. In the OLE at 1 and 1.5 years, the mean (SD) weight gain was 1.1 (5.9) kg and 0.5 (7.1) kg, respectively. SAEs were reported in 33 (12%) patients, 6 patients (2.2%) reported treatment-related SAEs. One SAE led to death (sudden unexpected death in epilepsy, considered not treatment related). The MPC was –83.4% at 18 months in the OLE vs DBP baseline. Updated safety and efficacy analyses will be presented.
Conclusions:
XEN1101 was generally well tolerated and demonstrated an OLE safety profile similar to that seen in the DBP and other antiseizure medications used in FOS treatment. No new safety signals emerged. These promising data suggest long-term efficacy of XEN1101 in a difficult-to-treat population.