Durable seizure frequency reduction with cenobamate

In a post-hoc efficacy analysis of an open-label phase 3 safety study of cenobamate, this anti-seizure medication was effective in the long term, yielding high rates of sustained (≥12 months) 100% seizure reduction. The results further support durable seizure frequency reduction with cenobamate in adults with uncontrolled focal seizures.

During the development of cenobamate, 3 cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred at starting doses of 50 or 100 mg/day. To mitigate the rate of DRESS, daily doses were started at 12.5 mg/day and slowly increased at 2-week intervals to the target dose of 200 mg/day over a 12-week period in an open‐label, multicentre, phase 3 study mandated by the FDA (NCT02535091). In 1,339 participants, no cases of DRESS were seen [1]. At the AAN 2021 meeting, post-hoc efficacy data from 10 US study sites from this study were presented [2]. Included in the analysis was available efficacy data of 240 patients with focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic seizure data while on treatment. Median duration of treatment was 30 months. Mean baseline seizure frequency per 28 days was 18.1.

A 100% seizure reduction with a duration of ≥12 months at the last visit or at any visit was seen in 62 patients (25.8%) and in 87 (36.3%), respectively. A 100% seizure reduction of ≥6 and ≥3 months at the last visit occurred in 84 (35.0%) and 107 (44.6%) patients, respectively. At the last visit, 177 patients (73.8%) were still using cenobamate. During the entire maintenance phase, 162 of 214 patients (75.7%) had a ≥50% responder rate; 29 (13.6%) had a ≥100% responder rate.

Another study analysed steady state trough plasma concentrations in patients who achieved 50% seizure reduction and seizure freedom in order to determine a reference concentration range for cenobamate [3]. A reference range of 5–35 µg/mL covered 95% of patients; it should be noted this is not a target therapeutic range.

1. Sperling ME, et al. Epilepsia. 2020 Jun;61(6):1099-1108.
2. Sperling MR, et al. Efficacy of Cenobamate for Uncontrolled Focal Seizures: Post-hoc Analysis of a Phase 3, Multicenter, Open-Label Study. S1.002, AAN 2021 Virtual Congress, 17-22 April.
3. Greene SA, et al. Cenobamate Trough Plasma Concentrations in Patients With Uncontrolled Focal Seizures Achieving 50% and 100% Seizure Reduction in Two Randomized Clinical Studies. S1.003, AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June, 2021