Abstract Details

Title Phase 2b Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy (X-TOLE)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-006

Background

XEN1101 is a novel, potent, selective KCNQ2/3 (Kv7.2/7.3) potassium channel positive allosteric opener being developed for focal onset seizures (FOS) and major depressive disorder. Its pharmacokinetic properties support once daily oral dosing without titration.

Objective

To assess the dose dependent efficacy, safety, and tolerability of XEN1101 as adjunctive treatment in adults with focal epilepsy.

Design/Methods

X-TOLE is a Phase 2b randomized, double-blind, placebo-controlled, dose-ranging study in adults with ≥4 countable FOS per month recorded with an eDiary, while receiving stable treatment with 1-3 antiseizure medications (ASMs). Subjects were randomized to one of three treatment groups or placebo in a 2:1:1:2 ratio (25 mg: 20 mg: 10 mg: placebo).

Results

A total of 325 patients with a median of 13.5 FOS per month at baseline were randomized and treated. The trial met its primary and secondary endpoints with XEN1101 demonstrating a dose-dependent reduction of 33.2% (p=0.035, n=46), 46.4% (p<0.001, n=51), and 52.8% (p<0.001, n=112) in the 10mg, 20mg, and 25mg groups, respectively, from baseline in median monthly FOS compared to placebo (18.2%, n=114). Response rates of ≥50% reduction in FOS were achieved in 28.3% (p=0.037), 43.1% (p<0.001) and 54.5% (p<0.001) in the 10mg, 20mg, and 25mg groups, respectively, compared to placebo (14.9%). Using CGI: 46.4% vs 22.8%(p<0.001) and PGI scales: 42.9% vs 21.9%(p=0.001) of patients were at least much improved with XEN1101 vs Placebo, respectively.

Incidence of TEAEs was 67.4%, 68.6%, and 85.1% in the 10mg, 20mg, and 25mg groups, respectively, compared to placebo (62.3%). Incidence of treatment-emergent SAEs was balanced across study arms. The overall dropout was 12.3%; 96.5% of study completers entered the OLE.

Conclusions

X-TOLE met all primary and secondary efficacy endpoints with XEN1101 demonstrating a statistically significant, dose-dependent, clinically relevant reduction from baseline in monthly focal seizure frequency compared to placebo. XEN1101 was well-tolerated; no adverse safety signal emerged.

Authors/Disclosures
Jacqueline French, MD, FAAN (NYU Comprehensive Epilepsy Ctr) PRESENTER	Dr. French has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Epilepsy Foundation. The institution of Dr. French has received research support from Epilepsy Study Consortium/ Epilepsy Foundation (Funded by UCB). The institution of Dr. French has received research support from GW/One8 Foundation/FACES. The institution of Dr. French has received research support from NINDS. The institution of Dr. French has received research support from Xenon. The institution of Dr. French has received research support from Cerevel. The institution of Dr. French has received research support from FACES. The institution of Dr. French has received research support from UCB. The institution of Dr. French has received research support from Epilepsy Study Consortium. The institution of Dr. French has received research support from UCB. Dr. French has received personal compensation in the range of $100,000-$499,999 for serving as a Chief Medical/Innovation Officer with Epilepsy Foundation. Dr. French has a non-compensated relationship as a Consultant with Angelini that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Alterity Therapeutics Limited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Bright minds Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cerecin Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cognizance Biomarkers that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Arvelle that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Beacon biosignals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Biohaven Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Bloom Science Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with BridgeBio Pharma Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant, scientific advisory board with Camp4 Therapeutics Corporation that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Scientific Advisory Board with Cerebral Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cerevel that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Coda Biotherapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Genentech Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Crossject that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Eisai, that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Eliem Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Encoded Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with iQure Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Engrail that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Epihunter that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Epiminder that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Epitel Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Equilibre BioPharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Greenwich Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Grin Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with GW Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Janssen Pharmaceutica that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Jazz Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Knopp Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Lipocine that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with LivaNova that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Longboard Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Lundbeck that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Marinus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Modulight Bio that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Leal therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neumirna Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant,SAB with Neurocrine that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neuroelectrics USA Corporation that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neuronetics Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Ono Pharmaceutical Co that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Otsuka Pharmaceutical Development that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Ovid Therapeutics Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Paladin Labs Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Rapport Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Praxis that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with PureTech LTY Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with SK Life Sciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Stoke that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Supernus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Takeda that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with UCB Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Ventus Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting, steering committee with Xenon that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Korro Bio Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with NeuroPro Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory board with Receptor that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory board with Sage Therpeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory Board with Third Rock Ventures that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Vida Ventures Management that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Pfizer that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Agrithera, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting with Autifony therapeutics, Unlimited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Baergic Bio that is relevant to AAN interests or activities.
Roger J. Porter, MD, FAAN	Dr. Porter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Xenon. Dr. Porter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Porter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Longboard. Dr. Porter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Engrail. Dr. Porter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axonis. Dr. Porter has received publishing royalties from a publication relating to health care.
Emilio Perucca	No disclosure on file
Martin Brodie	No disclosure on file
Michael A. Rogawski, MD, PhD (University of California - Davis)	Dr. Rogawski has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Xenon Pharmaceuticals.
	No disclosure on file
Ernesto Aycardi, MD (Kyowa Kirin)	Dr. Aycardi has received personal compensation for serving as an employee of XENON. Dr. Aycardi has received stock or an ownership interest from XENON.
Cynthia L. Harden, MD (Xenon Pharmaceuticals Inc)	Dr. Harden has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc.. Dr. Harden has stock in Xenon Pharmaceuticals Inc.. Dr. Harden has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Constanza Luzon	Constanza Luzon has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc.. Constanza Luzon has stock in Xenon Pharmaceuticals.
Christopher J. Kenney, MD, FAAN	Dr. Kenney has received personal compensation for serving as an employee of Xenon Pharmaceuticals. Dr. Kenney has stock in Xenon Pharmaceuticals.
Gregory N. Beatch, PhD	Dr. Beatch has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc. Dr. Beatch has stock in Xenon Pharmaceuticals Inc. Dr. Beatch has received intellectual property interests from a discovery or technology relating to health care.