Efficacy of Adjunctive Cenobamate by Focal Seizure Subtypes: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study in a Multinational Asian Population
Louis Ferrari1, Zhen Hong2, Kensuke Kawai3, Sunita Misra1, William Rosenfeld4, Peimin Yu2, Sang Kun Lee5
1SK Life Science, Inc., 2Fudan University, 3Jichi Medical University, 4Comprehensive Epilepsy Care Center for Children and Adults, 5Seoul national University Hospital
Objective:
To report the efficacy of adjunctive cenobamate by focal seizure subtype during the YKP3089C035 (C035) study.
Background:
Results from the recent multicenter, randomized, double-blind, placebo-controlled C035 study (NCT04557085) showed that adjunctive cenobamate 100, 200, and 400 mg/day significantly reduced focal-onset seizure frequency vs placebo in an Asian population with uncontrolled focal seizures.
Design/Methods:
Adults aged 18-70 years with ≥8 focal seizures (focal aware motor [FAM], focal impaired aware [FIA], or focal to bilateral tonic-clonic [FBTC]) during an 8-week baseline period despite treatment with 1-3 antiseizure medications were randomized 1:1:1:1 to either placebo or cenobamate 100, 200, or 400 mg once-daily. The study included an 18-week titration phase and 6-week maintenance phase and used the currently approved cenobamate titration schedule. Percent change from baseline in 28-day seizure frequency and responder rates for FAM, FIA, or FBTC seizure subtypes were assessed in the modified intent-to-treat maintenance phase population (MITT-M).
Results:
Among 519 patients randomized, 446 were in the MITT-M population; 79 (17.7%), 375 (84.1%), and 115 (25.8%) had FAM, FIA, and FBTC seizures at baseline, respectively. Patients may have had ≥1 seizure subtype. There were significant reductions in median 28-day seizure frequency from baseline during the maintenance phase in all assessed seizure subtypes vs placebo. Across subtypes, ≥50% responder rates were: FAM, 27.8% placebo vs 47.1% 100 mg (P=0.245), 85.7% 200 mg (P<0.001), and 82.6% 400 mg (P<0.001); FIA, 27.6% placebo vs 42.7% 100 mg (P=0.025), 64.9% 200 mg (P<0.001), and 80.0% 400 mg (P<0.001); FBTC, 68.8% placebo vs 66.7% 100 mg (P=0.859), 90.9% 200 mg (P=0.057), and 85.7% 400 mg (P=0.124). The most common treatment-emergent adverse events (≥20%) with cenobamate were dizziness and somnolence.
Conclusions:
This study supports the efficacy and safety profile of cenobamate using the approved titration regimen in a multinational Asian population. Statistically significant seizure reductions occurred across all assessed seizure subtypes.
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