Abstracts

Rationale: Cenobamate is an antiseizure medication (ASM) approved in the US for the treatment of adults with focal seizures. Recent data suggest that uncontrolled focal epilepsy patients with high responder rates to cenobamate (≥90% and 100%) have an improvement in quality of life (Elizebath R, et al. Epilepsy Behav. 2021;116:107796). The objective of this post-hoc analysis of the phase 3, open-label C021 study was to determine how likely cenobamate-treated patients who achieved ≥50%, ≥75%, ≥90%, or 100% response would be to maintain that response after 1 and 2 years.

Methods: Adults 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 ASMs were initiated on adjunctive cenobamate 12.5 mg/day for 2 weeks, with increasing daily doses (25, 50, 100, 150, and 200 mg) at 2-week intervals. Further increases to a maximum of up to 400 mg/day (using biweekly increments of 50 mg/day) were permitted during the Maintenance Phase. Seizure data were collected from patient diaries and clinic notes from 10 US study sites participating in C021. Response was defined as reduction in 28-day seizure frequency vs baseline, measured over approximately a 3-month period, that met specific response thresholds: ≥50%, ≥75%, ≥90%, and 100% among those who completed the 12-week Titration Phase. For a given response analysis, the index event for each patient was their first occurrence of that response at any point during the Maintenance Phase, if achieved. Maintaining response was measured using a Kaplan-Meier (KM) method for time to loss of response, defined as the first occurrence of 2 consecutive visits below the given response level after the index event.

Results: There were 240 patients in the intention-to-treat (ITT) group, 214 of whom completed the 12-week Titration Phase and received at least one dose of cenobamate in the Maintenance Phase (M-ITT). The baseline characteristics of the M-ITT group were similar to those of the ITT group and are reported elsewhere. Of the 214 total eligible patients in the M-ITT group, there were 188, 177, 160, and 145 patients who achieved a ≥50%, ≥75%, ≥90%, and 100% response at any point in the Maintenance Phase, respectively, and entered each level of response analysis. For each level of response (in ascending order), 84%, 75%, 72%, and 64% of patients maintained their response after 1 year and 73%, 67%, 60%, and 53% of patients maintained their response after 2 years (see Figures 1 and 2 for KM plots for the ≥90% and 100% analyses). After the initial loss of response events, the KM curves flattened and showed that patients with ≥50%, ≥75%, ≥90%, and 100% response rates had a ≥50% probability of maintaining the response through the 2.5-year follow-up period. Most patients exited the analysis due to the end of data collection.

Conclusions: Continued treatment with cenobamate resulted in a sustained response during the Maintenance Phase of therapy. In patients who achieved a ≥50%, ≥75%, ≥90% and 100% response, the response was durable through the end of approximately 2.5 years of follow-up.

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