Authors :
Presenting Author: Sunita N Misra, MD – SK Life Science, Inc.
Kensuke Kawai, MD, PhD – Jichi Medical University
Eunyeong Choe, RN – SK Biopharmaceuticals Co., Ltd
Louis Ferrari, RPh – SK Life Science, Paramus, New Jersey, USA
Kyoung Heo, MD, PhD – Yonsei University College of Medicine
Seung Bong Hong, MD, PhD, ABCN – Epilepsy & Sleep Center, St. Peter’s General Hospital
Huapin Huang, MD – Fujian Medical University Union Hospital
Koji Iida, MD, PhD – Hiroshima University Hospital
Yong Heui Jeon, PhD – SK Biopharmaceuticals Co., Ltd
Jiwon Jung, RPh, PhD – SK Biopharmaceuticals Co., Ltd
Marc Kamin, MD – SK Life Science, Inc.
Ji Hyun Kim, MD, PhD – Korea University Guro Hospital, Korea University College of Medicine
Myung Won Kim, RPh – SK Biopharmaceuticals Co., Ltd
SangKun Lee, MD, PhD – Seoul National University
Songqing Pan, MD – Renmin Hospital of Wuhan University (Hubei General Hospital)
Jungshin Park, RPh, PhD – SK Biopharmaceuticals Co., Ltd
Pranoti Pradhan, MD, MPH – SK Life Science, Inc.
William E. Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA
Huiqin Xu, MD – First Affiliated Hospital of Wenzhou Medical University
Takamichi Yamamoto, MD, PhD – Seirei Mikatahara General Hospital
Rationale:
Results from a recent multicenter, randomized, double-blind (DB), placebo-controlled study (YKP3089C035 [C035]) showed that adjunctive cenobamate (CNB) 100, 200, and 400 mg/day demonstrated early treatment responses in an Asian population, including a 42.9% median reduction in 28-day seizure frequency (Weeks 5-6, P=0.002) and a seizure-free rate of 26.7% (Weeks 7-8, P< 0.001). Patients who completed the 24-week DB treatment period were eligible to continue cenobamate in a 52-week open-label extension (OLE). In this interim analysis, we report treatment responses during the first 8 weeks of the OLE conversion phase (corresponding to Study Weeks 25-32) for patients originally randomized to PBO during the DB phase (PBO/CNB).Methods:
In the DB portion of the study, adults aged 18-70 years with ≥8 focal seizures during an 8-week baseline period despite treatment with 1-3 ASMs were randomized 1:1:1:1 to receive either adjunctive placebo or cenobamate 100, 200, or 400 mg once daily. Patients who entered the OLE underwent an 18-week blinded conversion to a target CNB dose of 400 mg/day at different rates, depending on their randomized group during the DB treatment period. Safety and tolerability were also assessed. Results:
For this interim analysis, 231 patients (mean age 35.7 years; 50.6% male) entered the OLE, including 168 originally randomized to CNB and 63 originally randomized to PBO who transitioned to CNB. Placebo patients were converted to cenobamate as follows: 12.5 mg/day for 2 weeks, then 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, and 100 mg/day for 2 weeks. Consistent with the early results in the DB treatment period, early responses to CNB treatment were observed during each 2-week interval during the first 8 weeks of the OLE conversion phase in the group converting from PBO. At Weeks 31-32, these included a 66.2% median reduction in seizure frequency (Figure 1) and a 100% responder rate of 31.3% at CNB 100 mg/day (Figure 2A-B) for PBO/CNB OLE patients. Among the 231 patients in the OLE, the most common TEAEs (≥20%) during the OLE were dizziness, somnolence, and COVID-19 infection. Conclusions:
As patients initially randomized to PBO during the DB study were converted to CNB during the OLE, early seizure reductions and treatment responses occurred in pattern generally similar to that observed in all CNB patients during the initial DB titration. This further supports that positive responses to CNB may be observed early during the currently approved titration schedule.Funding:
Funded by SK Biopharmaceuticals Co., Ltd. and SK Life Science, Inc.