Authors :
Presenting Author: William E. Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA
Xintong Wu, MD – Department of Neurology, West China Hospital of Sichuan University
Ling Chen, MD – First Affiliated Hospital of Kunming 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
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.
Kensuke Kawai, MD, PhD – Jichi Medical University
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
Sunita N Misra, MD – SK Life Science, Inc.
Jungshin Park, RPh, PhD – SK Biopharmaceuticals Co., Ltd
Tiancheng Wang, MD – Lanzhou University Second Hospital
Takamichi Yamamoto, MD, PhD – Seirei Mikatahara General Hospital
Peimin Yu, MD – Huashan Hospital, Fudan University
Rationale:
Results from a recent multicenter, randomized, double-blind (DB), placebo-controlled study (YKP3089C035 [C035]) showed that, compared to placebo, adjunctive cenobamate (CNB) 100, 200, and 400 mg/day significantly reduced focal-onset seizure frequency across all assessed seizure subtypes in a generally dose-responsive manner in an Asian population with uncontrolled focal seizures. During the 6-week maintenance phase, median reductions to 28-day seizure frequency in cenobamate-treated patients ranged from 48.9%-100% for focal aware motor (FAM) seizures (vs 26.1% placebo [PBO]) and from 42.6%-100% for focal impaired awareness (FIA) seizures (vs 26.2% PBO). For focal to bilateral tonic-clonic (FBTC) seizures, the median seizure frequency reduction was 100% for all cenobamate dose groups (vs 78.4% PBO). Patients who completed the 24-week DB treatment period were eligible to continue cenobamate in a 52-week open-label extension (OLE). Here we report interim efficacy data by focal seizure subtype from the ongoing C035 OLE.
Methods:
Adults aged 18-70 years with ≥8 focal seizures (FAM, FIA, or FBTC) 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 in the DB portion of the study. All patients who entered the OLE underwent an 18-week blinded conversion to a target CNB dose of 400 mg/day. Patients then entered the 32-week OLE maintenance phase starting on CNB 300 mg/day (dose 50-400 mg/day). Percent change from DB baseline in 28-day seizure frequency and responder rates (eg, ≥50% reduction from baseline) for FAM, FIA, or FBTC seizure subtypes were assessed in the OLE maintenance phase population (≥1 dose of study drug and any seizure data during OLE maintenance phase) by randomized group and overall. Safety and tolerability were also assessed.Results:
For this interim analysis, 231 patients (mean age 35.7 years; 50.6% male) entered the OLE, of which 184 were included in the OLE maintenance phase population (n=26 FAM, n=158 FIA, n=45 FBTC; patients may have had ≥1 seizure type). There were substantial reductions in median seizure frequency per 28 days from DB baseline during the open-label maintenance phase in all assessed seizure subtypes (Figure 1). There was a similar benefit in responder rates during the maintenance phase. Overall ≥50% responder rates were: FAM, 73.1% (19/26); FIA, 70.3% (111/158); FBTC, 77.8% (35/45). Overall 100% responder rates were: FAM, 19.2% (5/26); FIA, 29.1% (46/158); FBTC, 55.6% (25/45). Among the 231 patients in the OLE, the most common TEAEs (≥20%) during the OLE were dizziness, somnolence, and COVID-19 infection. Conclusions:
During the C035 OLE, seizure frequency reductions demonstrated during the DB treatment period were maintained or increased across all assessed seizure subtypes depending on the randomization group. These results further support the long-term efficacy of cenobamate for all focal seizure subtypes in adult patients.Funding:
Funded by SK Biopharmaceuticals Co., Ltd. and SK Life Science, Inc.