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
Abstract number :
1.277
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2023
Submission ID :
134
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Jacqueline French, MD – New York University Grossman School of Medicine and NYU Langone Health, New York, NY
Roger Porter, MD – University of Pennsylvania, Philadelphia, PA; Emilio Perucca, MD, PhD – Monash University, Melbourne, Victoria, Australia, and University of Melbourne (Austin Health), Heidelberg, Victoria, Australia; Martin Brodie, MD – University of Glasgow Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland; Michael Rogawski, MD, PhD – School of Medicine, University of California, Davis, Sacramento, CA; Cynthia Harden, MD – Xenon Pharmaceuticals Inc., Vancouver, BC, Canada; Jenny Qian, MS – Xenon Pharmaceuticals Inc., Vancouver, BC, Canada; Constanza Luzon Rosenblut, MD – Xenon Pharmaceuticals Inc., Vancouver, BC, Canada; Christopher Kenney, MD – Xenon Pharmaceuticals Inc., Vancouver, BC, Canada; Gregory Beatch, PhD – Xenon Pharmaceuticals Inc., Vancouver, BC, Canada
Rationale: XEN1101 is a potent, selective KV7 potassium channel opener in development as a treatment for epilepsy. In a randomized, double-blind, placebo-controlled phase 2b study (X-TOLE) in patients with focal onset seizures (FOS), XEN1101 (10, 20, and 25 mg QD with food) showed a dose-dependent, highly statistically significant, and rapid-onset reduction in seizure frequency. We previously reported early results from the ongoing open-label extension (OLE) and now report longer-duration interim safety and efficacy data.
Methods: On completion of the double-blind period (DBP), eligible patients enrolled in the five year OLE at 20 mg QD in the fed state. Assessments were performed at week three in the OLE and at three month intervals thereafter. Safety assessments included frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) and clinically significant changes in laboratory findings. The primary efficacy outcome was median percentage change (MPC) in monthly (28-day) FOS frequency from DBP baseline.
Results: Of the 285 patients completing the DBP, 275 (96.5%) enrolled in the OLE. At DBP baseline, these patients had a median of 13.3 FOS per month and were on stable treatment with one to three antiseizure medications (ASMs), with 52% taking three concomitant ASMs. At interim analysis of the ongoing OLE (data cut April 12, 2023), 182 had been treated for ≥1 year and 170 for ≥18 months; 159 (57.8%) patients continued participation. The most common reasons for discontinuation were lack of efficacy (13.1%), adverse events (12.0%), and study withdrawal by patient (11.3%). 86.9% of the patients reported ≥1 TEAE, and 61.5% reported a treatment-related TEAE. The majority of TEAEs were mild or moderate; 14.5% reported severe TEAEs. The most common TEAEs were dizziness (20.7%), coronavirus infection (16.0%), headache (15.3%), fall (11.6%), and somnolence (10.5%). 20.7% reported TEAEs leading to dose reduction. The mean (SD) weight gain at 1 year was 1.1 (5.9) kg and 0.5 (7.1) kg at 1.5 years in the OLE. SAEs were reported in 33 (12.0%) patients; 6 (2.2%) were considered treatment related. There was one SAE leading to death, a sudden unexpected death in epilepsy case reported as not treatment related. The MPC was –83.4% at 18 months in the OLE vs the DBP baseline. Updated safety and efficacy analyses will be presented.
Conclusions: In the X-TOLE OLE, XEN1101 was generally well tolerated and demonstrated a safety profile similar to that seen in the DBP and with other ASMs used in the treatment of FOS. No new safety signals emerged. This promising interim data suggests long-term efficacy of XEN1101 in a difficult-to-treat population.
Funding: Xenon Pharmaceuticals Inc.
Anti-seizure Medications