Long-Term Quality-of-Life Improvements in Adults with Focal Onset Seizures Treated with XEN1101 in an Ongoing Open-Label Extension of a Phase 2b Study (X-TOLE)
Abstract number :
2.26
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2023
Submission ID :
545
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
First Author: Christian Brandt, MD – Bethel Epilepsy Centre, Mara Hospital, University Hospital for Epileptology, Bielefeld, Germany
Presenting Author: Constanza Luzon Rosenblut, MD – Xenon Pharmaceuticals Inc.
Vicente Villanueva, MD – Refractory Epilepsy Unit, Hospital Universitario Y Politécnico La Fe, Valencia, Spain; 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; Joanne Wagner, PhD – 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:
The patient perception of well-being and functional capabilities is a critical outcome of clinical care, measured by quality-of-life (QoL) assessments that evaluate the impact of treatment interventions. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) is a validated tool that provides an overall QoL assessment and additional insights into the patients’ self-perceived health status and includes evaluations of specific functional and psychosocial domains. In a randomized, double-blind, placebo-controlled phase 2b study (X-TOLE) in adult patients with focal onset seizures (FOS), XEN1101, a potent, selective Kv7 potassium channel opener, showed a dose-dependent, highly statistically significant, and rapid onset seizure frequency reduction. We report interim QOLIE-31 results from the ongoing, long-term, open-label extension (OLE) of X-TOLE. This is the first large epilepsy study for XEN1101; the long-term QoL assessments will bring insight into the patient-perceived effects of treatment.
Methods:
On completion of the double-blind period (DBP), eligible patients transitioned to the OLE at 20 mg QD in the fed state. Beginning at week 15 in the OLE, the QOLIE-31 was completed at three month intervals for the first year, then every six months thereafter. Results are reported for the OLE at 1.5 years compared to the double-blind baseline assessment. Minimally important change (MIC) thresholds in QOLIE-31 scores (Borghs et al. Epilepsy Behav 2012;23:230-4) were applied to the overall group and seizure-free group.
Results:
A total of 285 patients completed the DBP and 275 (96.5%) enrolled in the OLE. In the interim analysis (data cut April 12, 2023), 170 patients were treated for ≥18 months in the ongoing X-TOLE OLE, and monthly (28-day) FOS median reduction at 18 months was 83.4%. Of these patients, 33 (19.4%) were seizure-free for ≥12 consecutive months. At 1.5 years, QOLIE-31 subscale scores met the MIC threshold for improvement in the overall and seizure-free groups, as follows: overall QoL of 6.4 and 13.2 points, respectively, seizure worry of 12.8 and 23.7 points, and social functioning of 8.3 and 22.3 points. Additionally, for the seizure-free group only, QOLIE-31 subscale scores met the MIC threshold for improvement for energy/fatigue (6.4 points), cognitive functioning (10.6 points), medication effects (15.2), and QOLIE-31 total score (13.1).
Conclusions:
The overall group achieved important QoL improvements following long-term XEN1101 treatment, including overall QoL, seizure worry, and social functioning. Seizure worry and social functioning are meaningful QoL domains because they are associated with seizure severity (Harden et al. Epilepsy Behav 2007;11:208-11). The seizure-free patients had self-reported improvement in cognitive functioning and reduced medication adverse effects as well as other positive QOLIE-31 changes with XEN1101 treatment, indicating that this subgroup of patients are achieving the goal of antiseizure medicine therapy, which is seizure freedom with minimal adverse effects.
Funding:
Xenon Pharmaceuticals Inc.
Anti-seizure Medications