Efficacy and safety of adjunctive cenobamate based on patient etiology: Post-hoc analysis of YKP3089C017 randomized clinical trial

Jie Xu; Wei Wei; Yutong Liu; Hui Ye; Xiaorong Liu

doi:10.1016/j.seizure.2024.04.017

Efficacy and safety of adjunctive cenobamate based on patient etiology: Post-hoc analysis of YKP3089C017 randomized clinical trial

Seizure. 2024 Apr 22:118:95-102. doi: 10.1016/j.seizure.2024.04.017. Online ahead of print.

Authors

Jie Xu¹, Wei Wei¹, Yutong Liu², Hui Ye², Xiaorong Liu³

Affiliations

¹ Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China.
² Ignis Therapeutics (Shanghai) Limited, Shanghai 200000, China.
³ Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China. Electronic address: happyxiaorongo@163.com.

PMID: 38652999
DOI: 10.1016/j.seizure.2024.04.017

Abstract

Introduction: Adjunctive cenobamate was effective and safe for the treatment of uncontrolled focal onset seizures in a randomized, double-blind, placebo-controlled, phase 2 study (YKP3089C017; NCT01866111). This post-hoc analysis assessed the efficacy of adjunctive cenobamate in the treatment of patients with different epileptic etiologies during the study.

Methods: Adult patients with uncontrolled focal seizures who previously received 1 to 3 antiseizure medications (ASMs) were randomly assigned in a ratio of 1:1:1:1 to receive placebo or cenobamate 100, 200 or 400 mg/day. Patients were further stratified based on their etiologic causes as genetic/presumed genetic, unknown cause, structural cause, and not reported (NR) groups. The frequency per 28 days for an 18-week double-blind treatment period, responder rates (≥50 %, ≥75 %, ≥90 %, and 100 %) during the maintenance phase (12 weeks), and safety were assessed.

Results: A total of 394 patients were categorized into the genetic/presumed genetic (n = 9; 2.28 %), unknown cause (n = 199; 50.51 %), structural cause (n = 177; 44.92 %), and NR (n = 13; 3.30 %) groups, with 4 patients were classified into either of the two etiological causes each. The baseline characteristics were comparable. The percentage of reduction in seizure frequency per 28 days was significantly higher in the cenobamate-treated structural (p = 0.01) and unknown cause (p = 0.0003) groups compared with the placebo group. Responder rates of ≥50 %, ≥75 %, ≥90 %, and 100 % were also higher with cenobamate therapy. Notably, no serious treatment-emergent adverse events (TEAEs) were observed in the genetic/presumed genetic group treated with cenobamate. The most common TEAEs (≥10 %) occurring in patients treated with cenobamate were nervous system disorders by system organ class, and somnolence was the most commonly reported TEAE.

Conclusion: Cenobamate reduces seizures in adult patients previously treated with ASMs, with high responder rates and acceptable safety, regardless of underlying causes.

Keywords: Antiseizure medication; Cenobamate for different epilepsy etiology; Epilepsy etiology; Focal epilepsy; Structural epilepsy.