The Impact of Disease Severity on Efficacy from a Phase 2b Study of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy (X-TOLE)
Abstract number :
2.233
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2204695
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Jennifer Leung, MSc – Xenon Pharmaceuticals, Inc; Jackie French, MD – NYU Grossman School of Medicine; Roger Porter, MD – University of Pennsylvania; Emilio Perucca, MD, PhD – The University of Melbourne; Martin Brodie, MD – University of Glasgow; Michael Rogawski, MD, PhD – University of California, Davis; Cynthia Harden, MD – Xenon Pharmaceuticals; Jenny Qian, MS – 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 the X-TOLE Phase 2b study, XEN1101 (10, 20, and 25 mg QD) showed a dose-dependent, highly statistically significant, and rapid onset reduction in FOS frequency in patients who had failed a median of 6 anti-seizure medications (ASMs) with 50.8% of patients on 3 background ASMs. Patients in the study had ≥4 FOS per month at baseline and were on stable treatment with 1-3 ASMs. In this analysis, the potential impact of disease severity on efficacy in X-TOLE was assessed.
Methods: A total of 325 subjects were randomized and treated across 3 treatment groups or placebo in a 2:1:1:2 ratio (25 mg: 20 mg: 10 mg: placebo). Post-hoc analyses to assess the influence of disease severity on the response were performed. Evaluations were made based on baseline seizure burden, number of prior failed ASMs, and concomitant ASMs during the study. The data presented pertain to the 25 mg treatment group.
Results: Subjects with ≤8.5 seizures/month at baseline experienced a 70.6% reduction compared with 50.8% for those with >8.5 seizures/month. Median monthly FOS reduction was 58% in subjects who failed ≤6 ASMs at baseline and 43% in subjects who failed >6 ASMs. Median monthly FOS reduction was 60.9% for subjects with 1 to 2 concomitant ASMs and 50.8% for subjects with 3 concomitant ASMs.
Conclusions: In the overall analysis, XEN1101 treatment was associated with statistically significant reductions in monthly FOS frequency at all doses evaluated. The study included subjects with various degrees of disease severity based on seizure burden, prior failed ASMs, and concomitant ASMs. The present post-hoc analysis suggests that XEN1101 is effective in patients with both severe and less severe disease. As expected with any ASM, however, XEN1101 is relatively more effective in patients with less severe disease. Although the study population was generally difficult to treat, these results indicate that XEN1101 is appropriate for use in a broad range of patients with focal epilepsy.
Funding: Xenon Pharmaceuticals, Inc.
Anti-seizure Medications