Long-term Efficacy of Adjunctive Cenobamate: Open-label Extension of a Randomized Clinical Study in a Multinational Asian Population
Louis Ferrari1, Sang Kun Lee2, Peimin Yu3, Eunyeong Choe4, Kyoung Heo5, Seung Bong Hong6, Zhen Hong3, Koji Iida7, Yong Heui Jeon4, Jiwon Jung4, Marc Kamin1, Kensuke Kawai8, Ji Hyun Kim9, Myung Won Kim4, Xiaorong Liu10, Sunita Misra1, Jungshin Park4, William Rosenfeld11, Takamichi Yamamoto12, Dong Zhou13, Suiqiang Zhu14
1SK Life Science, Inc., 2Seoul National University College of Medicine, 3Huashan Hospital, Fudan University, 4SK Biopharmaceuticals Co., Ltd., 5Yonsei University College of Medicine, 6Epilepsy & Sleep Center, St. Peter’s General Hospital, 7Hiroshima University Hospital, 8Jichi Medical University, 9Korea University Guro Hospital, Korea University College of Medicine, 10Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical University, 11Comprehensive Epilepsy Care Center for Children and Adults, 12Seirei Mikatahara General Hospital, 13West China Hospital of Sichuan University, 14Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Objective:
To report interim efficacy and safety from the YKP3089C035 (C035) open-label extension (OLE) study.
Background:
Results from the multicenter, randomized, double-blind, placebo-controlled C035 study in a multinational Asian population with uncontrolled focal seizures showed that adjunctive cenobamate 100, 200, and 400 mg/day significantly reduced focal-onset seizure frequency in a dose-responsive manner.
Design/Methods:
In C035, adults 18-70 years old with ≥8 focal seizures during an 8-week baseline despite treatment with 1-3 antiseizure medications were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400 mg/day. Patients entering the OLE underwent an 18-week blinded conversion to cenobamate target dose of 400 mg/day. Then to maintain blinding, all patients entered the 32-week OLE maintenance phase starting at cenobamate 300 mg/day (doses could be adjusted from 50-400 mg/day). Percent change from double-blind baseline in 28-day focal seizure frequency and responder rates were assessed in the OLE maintenance phase efficacy population (OLE-EM, ≥1 dose of study drug and any seizure data during OLE maintenance phase). Safety was also assessed.
Results:
This OLE interim analysis included 231 patients (mean age 35.7 years; 50.6% male). Of these, 184 were included in the OLE-EM population (136 originally randomized to cenobamate; 48 transitioned from placebo). Median percent reductions of 76.8%, 84.5%, 90.6%, and 85.1% were demonstrated for patients originally randomized to placebo and cenobamate 100, 200, and 400 mg/day, respectively. Responder rates of ≥50% and 100% by original randomization group were: 67% and 17% for placebo; 71% and 25% for cenobamate 100 mg/day; 76% and 24% for cenobamate 200 mg/day; and 69% and 36% for cenobamate 400 mg/day. TEAEs reported in ≥20% of patients were dizziness, somnolence, and COVID-19 infection. Serious TEAEs occurred in 10% (23/231) of patients.
Conclusions:
Reductions in seizure frequency increased or were maintained during the 32-week OLE maintenance phase. The safety profile was generally consistent with the double-blind phase.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.