Cenobamate shows long-term safety and effectiveness in uncontrolled partial seizures

Adjunctive cenobamate has been associated with an early and high rate of sustained seizure reductions in adult patients with uncontrolled partial seizures, according to research published in Epilepsia.

Many patients with epilepsy require lifelong treatment with anti-epileptic drugs (ASMs), but an estimated 35-40% of newly diagnosed patients cannot use these drugs to maintain seizure freedom. Uncontrolled seizures can lead to a higher risk of mortality and morbidity compared to the general population. Cenobamate, an ASM from the US Food and Drug Administration (FDA), has shown a favorable safety and tolerability profile, but its effects on long-term seizure outcomes are still unknown.

The aim of the current study was to perform a post hoc analysis focusing on the long-term efficacy and safety data of an open-label Phase 3 study of cenobamate in patients with uncontrolled partial seizures.

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The study included 255 patients with uncontrolled partial seizures who received stable doses of 1 to 3 anti-epileptic drugs (ASM). Participant data are from a phase 3 open label safety study in which the safety and tolerability of cenobamate was reported in 1347 patients (NCT02535091). A total of 240 patients in the study had data on focal conscious motor, focal impairment of consciousness or focal to bilateral tonic-clonic seizures during 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 dose of cenobamate was then increased by 50 mg / day every 2 weeks to achieve a target dose of 200 mg / day. Investigators allowed additional increases in increments of 50 mg / day biweekly 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 study was 30.2 months. At the time of the data cut-off, 73.8% (n = 177) of the patients were still being treated with cenobamate.

The researchers rated the response rates of ≥ 50%, ≥ 75%, ≥ 90%, and 100% throughout the treatment period. Patients were counted as 50%, ≥75%, ≥90%, and ≥100% responders if they had a ≥50%, ≥75%, ≥90%, or ≥100% reduction in seizure frequency from baseline every 4- Week interval.

During the entire treatment period, the responder rate was ≥ 50 71.7%. Response rates of ≥ 50% during the titration periods were 48.1% in weeks 1 to 4 and 61.7% in weeks 5 to 8.

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

The most commonly reported treatment-related adverse reactions across the patient population were fatigue (34.6%), dizziness (32.1%), and drowsiness (29.6%).

The limitations of the study included the lack of a comparator arm and its open nature, which the investigators said was not specifically designed to evaluate the effectiveness of the treatment.

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

Disclosure: This clinical study was supported by SK Life Science. Several authors stated links with the pharmaceutical industry. For a full list of the details, see the original article.


Sperling MR, Abou-Khalil B, Abumatar S, et al. Efficacy of cenobamate in uncontrolled partial seizures: post-hoc analysis of a multicenter, open-label phase 3 study. Epilepsy. Published online October 11, 2021. doi: 10.1111 / epi.17091

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