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
Abstract number :
2.235
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2204706
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Jacqueline French, MD – NYU Grossman School of Medicine; Roger Porter, MD – University of Pennsylvania; Emilio Perucca, MD, PhD – Department of Medicine (Austin Health) – The University of Melbourne; Martin Brodie, MD – University of Glasgow; Michael Rogawski, MD, PhD – School of Medicine – University of California, Davis; Cynthia Harden, MD – Xenon Pharmaceuticals; Jenny Qian, MS – Xenon Pharmaceuticals; Constanza Luzon-Rosenblut, MD – Xenon Pharmaceuticals; Christopher Kenney, MD, FAAN – Xenon Pharmaceuticals; Greg Beatch, PhD – Xenon Pharmaceuticals
Rationale: XEN1101 is a novel, potent, selective KCNQ2/3 (Kv7.2/7.3) potassium channel opener, currently 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) showed a dose-dependent, highly statistically significant, and rapid onset reduction in seizure frequency. Patients in the study had ≥4 FOS per month at baseline and were on stable treatment with 1 to 3 anti-seizure medicines (ASMs), with 50.8% on 3 background ASMs. We now report long-term outcomes as measured in the X-TOLE open-label extension (OLE).
Methods: On completion of the double-blind period (DBP), eligible patients were considered for OLE enrollment at 20 mg QD. Assessments were performed at Week 3 in the OLE and 3-month intervals thereafter. 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%) enrolled in the OLE. In the interim analysis of the ongoing OLE, 178 patients continued participation; 206 had been treated for ≥6 months and 101 treated for ≥1 year. The most common reasons for discontinuation were lack of efficacy (12%), AEs (10.2%), and study withdrawal by the patient (8%); 82.2% of the total safety population reported a TEAE. The majority of TEAEs were considered related to study drug and were mild or moderate, while 10.2% reported severe TEAEs. The most common TEAEs were dizziness (19.6%), headache (13.1%), somnolence (9.8%), weight increased (8.7%), fall (8%), gait disturbance (8%), fatigue (5.8%), confusional state (5.5%), aphasia (5.1%), and memory impairment (5.1%). 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). 18.5% reported TEAEs leading to dose reduction. SAEs were reported in 20 (7.3%) patients with 6 (2.2%) considered treatment related. The average (mean ± SD) weight gain at the 6-month visit was 1.4 ± 4.5 kg and 0.9 ± 6.2 kg at 1 year, respectively. 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 to other ASMs used in patients with focal epilepsy; no new safety signals emerged.
Funding: Xenon Pharmaceuticals, Inc.
Anti-seizure Medications