Abstracts

Rationale: Cenobamate, an antiseizure medication (ASM) approved in the US, Canada, and Europe for the treatment of focal seizures in adults, has demonstrated good efficacy in focal seizures. Results from a recent multicenter, randomized, double-blind, placebo-controlled study (YKP3089C035 [C035]) showed that adjunctive cenobamate (CNB) 100, 200, and 400 mg/day significantly reduced focal-onset seizure frequency compared to placebo in an Asian population with uncontrolled focal seizures. Here we report the efficacy of adjunctive cenobamate by focal seizure subtype during the C035 study.

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 ASMs were randomized 1:1:1:1 to receive either adjunctive placebo or cenobamate 100, 200, or 400 mg once daily. The study included an 18-week titration phase and a 6-week maintenance phase and used the currently approved cenobamate titration schedule. Percent change from baseline in 28-day seizure frequency and responder rates (≥50%, ≥75%, ≥90%, and 100% reduction from baseline) for FAM, FIA, or FBTC seizure subtypes were assessed in the modified intent-to-treat maintenance phase population (MITT-M, ≥1 dose of study drug and ≥1 efficacy measure during maintenance phase). Safety and tolerability were also assessed.

Results: Among 519 patients randomized, 516 received ≥1 dose of study drug and 446 were included in the MITT-M population. Of these 446 patients, 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 seizure frequency per 28 days from baseline during the maintenance phase in all assessed seizure subtypes compared to placebo (Figure 1). There was a similar significant benefit in responder rates during the maintenance phase. The ≥50% responder rates were as follows: 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 TEAEs (≥20%) were dizziness and somnolence in the cenobamate dose groups.

Conclusions: This study supports the efficacy and safety profile of cenobamate using the approved titration regimen in a multinational Asian population. Significant seizure reductions occurred across all assessed seizure subtypes.

Funding: Funded by SK Life Science, Inc.