XEN1101, a Novel Potassium Channel Modulator: Interim Data From an Ongoing, Long-Term, 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, New York, NY, USA, 2University of Pennsylvania, Philadelphia, PA, USA, 3Monash University, Melbourne, Victoria, Australia and Austin Health, University of Melbourne, Heidelberg, Victoria, Australia, 4University of Glasgow, Glasgow, UK, 5University of California - Davis, Sacramento, CA, USA, 6Xenon Pharmaceuticals Inc., Burnaby BC, Canada
Objective:
Report interim data from an ongoing, long-term, open-label extension of a phase 2b study (X-TOLE) of XEN1101 in adults with focal epilepsy.
Background:
XEN1101 is a novel, potent, selective Kv7.2/7.3 potassium channel opener shown to be effective in a randomized, double-blind, placebo-controlled Phase 2b study in patients with focal onset seizures (FOS). We now report long-term outcomes from the X-TOLE open-label extension (OLE).
Design/Methods:
After the double-blind period (DBP), eligible patients began the OLE at 20 mg QD in the fed state. Safety was assessed as severity and frequency of treatment emergent adverse events (TEAEs) and serious AEs (SAE), clinically significant changes in laboratory findings and other measures. The primary efficacy outcome was median percent change in monthly FOS frequency from DBP baseline and monthly response rate (≥50% reduction from DBP baseline in monthly FOS frequency).
Results:
Of the 285 subjects completing the DBP, 275 (96.5%) entered the OLE. In this interim analysis of the ongoing OLE, the retention rate at 1 year was 68%. The most common TEAEs were dizziness, headache, somnolence, weight increased, fall, gait disturbance, fatigue, confusional state, aphasia, and memory impairment. No TEAEs of pigmentary abnormalities were reported. Two patients experienced TEAEs of urinary retention (1 mild, 1 moderate, possibly drug related, but both patients continued the medication). The average (mean ± SD) weight gain at the 6-month visit was 1.4 ± 4.5 kg. Updated safety and efficacy analyses will be presented.
Conclusions:
In the X-TOLE OLE, XEN1101 20 mg was generally well-tolerated and demonstrated a safety profile similar to the DBP and other anti-seizure medicines used in patients with focal epilepsy; no new safety signals emerged.