Abstracts

Rationale: Cenobamate is an antiseizure medication (ASM) approved in the US in 2020 for the treatment of adults with focal seizures. Here we report post-hoc retrospective efficacy data by focal seizure subtypes from 10 US study sites from a global, long-term, open-label phase 3 study.

Methods: Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled. Increasing daily doses of cenobamate were administered (12.5, 25, 50, 100, 150, and 200 mg/day) at 2-week intervals. Further increases to 400 mg/day by 50 mg/day increments every other week were allowed. Patient visits occurred every 2 weeks for 16 weeks and then every 1-3 months. Adjustments to concomitant ASMs were allowed during the study. Cenobamate monotherapy was not allowed.

Results: 240 patients from US sites with focal aware motor (FAM), focal impaired awareness (FIA), and focal to bilateral tonic-clonic (FBTC) seizure data were evaluated. Of the 240 patients, 177 (73.8%) were continuing cenobamate at the last clinic visit on or after September 1, 2019 (mean duration 32.9 months). Twenty-seven (11.3%), 223 (92.9%), and 56 (23.3%) patients had FAM, FIA, and FBTC seizure subtypes, respectively (patients may have had more than 1 seizure subtype). Median baseline seizure frequencies/28 days were 10.5, 2.3, and 0.9 for patients with FAM, FIA, and FBTC seizure subtypes. The median percent change in seizure frequency/28 days from baseline showed the greatest decrease in seizure frequency in the FBTC seizure subtype at each 3-month interval through Months 9-12 (Figure 1). Median percent decreases after Months 9-12 were more similar among the 3 seizure subtypes through Months 24-27 (Figure 1). The percentage of patients achieving 50% seizure reduction was greatest among the FBTC seizures subtype during Months 1-3, followed by similar percentages among the FBTC and FAM seizure subtypes during the next 3-month interval (Months 3-5) through Months 9-12 (Figure 2A). After Months 9-12, the percentages of patients achieving 50% seizure reduction were more similar among all 3 seizure subtypes (Figure 2A). The percentage of patients achieving 100% seizure reduction in the FAM, FIA, and FBTC seizure subtypes was 22.2% (6/27), 21.5% (48/223), and 50% (28/56) during Months 1-3 and increased to 47.8% (11/23), 54.3% (88/162), and 90.5% (38/42) during Months 24-27, respectively (Figure 2B).The most common treatment-emergent adverse events (≥20%) in the long-term US cohort (n=240) were fatigue, dizziness, and somnolence. No cases of DRESS were reported.

Conclusions: The FBTC seizure subtype had an early onset of seizure frequency reduction, followed by similar reductions among all 3 seizure subtypes. Reductions were sustained through Months 24-27. Together, with the high retention rate and 100% seizure reduction rates, these data support the long-term efficacy of cenobamate across a variety of seizure types.

Funding: Please list any funding that was received in support of this abstract.: Funded by SK Life Science, Inc.