Abstracts

Rationale: Cenobamate is approved in the US for treatment of focal seizures in adults. Here we report the efficacy of cenobamate treatment in patients with uncontrolled focal seizures who had previous epilepsy-related surgery (resection, corpus callosotomy, tumor removal, ablation, vagus nerve stimulation [VNS] or responsive neurostimulation [RNS]) in a post-hoc analysis of the open-label C021 safety study.

Methods: Adults 18-70 years old with uncontrolled focal seizures on stable doses of 1-3 antiseizure medications (ASMs) were enrolled in the long-term, global, phase 3, open-label study (N=1347 enrolled). Dose increases of cenobamate (from 12.5 to 25, 50, 100, 150, 200 mg/day) occurred biweekly. Further increases up to 400 mg/day by 50-mg/day increments biweekly were permitted during a maintenance phase. Adjustments to concomitant ASMs were allowed. Cenobamate monotherapy was not allowed. Patient visits occurred every 2 weeks for 16 weeks and then every 1-3 months. A protocol amendment permitted the post-hoc collection of focal seizure data. Efficacy was examined in all patients with seizure data as the percentage of patients achieving seizure freedom (SF) ≥12 months (ie, 100% seizure reduction) at the last clinic visit and ≥12 months at any interval (ie, does not have to include the last visit). Efficacy was examined in patients still receiving cenobamate as SF ≥12 months at the data cut-off visit.

Results: Focal seizure data were available for 240 patients from 10 eligible US study sites and 177 patients were still receiving cenobamate as of data cut-off (mean duration of time on-study was 33.6 months). Of the 240 patients, 85 (35.4%) had prior epilepsy-related surgery: 40 patients had ≥1 procedure that were not VNS/RNS; 31 patients had VNS/RNS only; and 14 patients had both VNS and a resection, ablation, or disconnection surgery. In these 85 patients, 23.5% (20/85) had SF≥12 months at the last clinic visit and 30.6% (26/85) had SF≥12 months at any interval. Of the 177 patients still receiving cenobamate, 65 had prior epilepsy-related surgery and 29.2% (19/65) had SF ≥12 months at data cut-off (mean duration was 23.5 months). The corresponding SF ≥12 months outcomes for nonsurgical patients were 27.1% (42/155; last clinic visit), 39.4% (61/155; any interval), and 26.5% (41/155; ongoing patients at data cut-off) (Figure 1). Across surgical procedures, SF for ≥12 months with cenobamate treatment ranged from 20% to 35.7% of patients (Figure 2).

Conclusions: In this post-hoc analysis, high rates of sustained seizure freedom (≥12 months) were achieved with cenobamate in adult patients with uncontrolled focal seizures who were refractory to prior epilepsy-related surgery as well as to 1-3 ASMs. These findings support cenobamate as highly effective even in patients with very refractory seizures despite surgery and suggest cenobamate should be considered early in the treatment regimen, including prior to surgery.

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