Cenobamate Shows Long-Term Safety and Efficacy in Uncontrolled Focal Seizures

Adjunctive cenobamate was associated with early and high rates of sustained seizure reductions in adult patients with uncontrolled focal seizures, according to research findings published in Epilepsia.

Many patients with epilepsy require life-long treatment with antiseizure medications (ASMs), but for an estimated 35%-40% of newly diagnosed patients, these medications are unable to sustain seizure freedom. Uncontrolled seizures can lead to a higher risk for mortality and morbidity compared with the general population. Cenobamate, a US Food and Drug Administration (FDA) ASM, has shown a favorable safety and tolerability profile, but its effect on long-term seizure outcomes remains unknown.

The objective of the current study was to conduct a post-hoc analysis that would focus on the long-term efficacy and safety data from an open-label phase 3 study of cenobamate in patients with uncontrolled focal seizures. 

The study included 255 patients with uncontrolled focal seizures who were on stable doses of 1 to 3 antiseizure medications (ASMs). Participant data were obtained from an open-label, phase 3 safety study that reported the safety and tolerability of cenobamate in 1347 patients (NCT02535091). A total of 240 patients in the study had focal aware motor, focal impaired awareness, or focal to bilateral tonic–clonic seizure data while on therapy and were included in the analysis.

Patients received daily doses of cenobamate, starting at 12.5 mg/day for 2 weeks, then 25 mg/day for 2 weeks and followed by 50 mg/day for 2 weeks. The cenobamate dose was subsequently increased by 50 mg/day every 2 weeks to reach a target dose of 200 mg/day. The investigators allowed additional increases, in 50 mg/day biweekly increments, up to 400 mg/day during the maintenance phase.

At baseline, the median seizure frequency per 28 days was 2.8, while the mean was 18.1. The median treatment exposure during the open-label study was 30.2 months. At data cutoff, 73.8% (n=177) of patients were still on treatment with cenobamate.

Researchers assessed the ≥50%, ≥75%, ≥90%, and 100% responder rates during the entire treatment period. Patients counted as ≥50%, ≥75%, ≥90%, and ≥100% responders if they had a ≥50%, ≥75%, ≥90%, and ≥100% reduction from baseline, respectively, in seizure frequency during each 4-week interval.  

During the entire treatment duration, the ≥50 responder rate was 71.7%. The ≥50% responder rates during the titration periods were 48.1% during weeks 1 through 4 and 61.7% during weeks 5 through 8.

Approximately 13.1% of patients achieved a 100% seizure reduction and 40.2% of patients achieved a ≥90% seizure reduction during the overall maintenance phase (N=214; median, 29.5 months). In all patients, approximately 36.3% (n=87) experienced any consecutive ≥12-month duration of total (100%) seizure reduction.

The most frequently reported treatment-emergent adverse events in the overall patient population were fatigue (34.6%), dizziness (32.1%), and somnolence (29.6%).

Limitations of the study included its lack of a comparator arm as well as its open-label nature, which the investigators stated was not designed to evaluate treatment efficacy specifically.

Despite these limitations, the investigators wrote that their “findings suggest that cenobamate is safe and effective during long-term treatment” in patients with uncontrolled focal seizures.

Disclosure: This clinical trial was supported by SK Life Science. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Sperling MR, Abou-Khalil B, Aboumatar S, et al. Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study. Epilepsia. Published online October 11, 2021. doi:10.1111/epi.17091