Abstracts

Rationale: Cenobamate is an antiseizure medication (ASM) approved in the US and EU for the treatment of adults with focal seizures. Many patients with epilepsy require adjunctive therapy, which can increase their ASM drug load. Higher drug load may lead to higher rates of treatment emergent adverse events (TEAEs) and serious TEAEs. This post-hoc analysis evaluated changes in concomitant ASM drug load after adding cenobamate and any concurrent efficacy changes in patients from 10 U.S. study sites from the open-label phase 3 safety study (Sperling et al. 2020).

Methods: Patients 18 to 70 years old with uncontrolled focal seizures taking stable doses of 1 to 3 ASMs were enrolled. Dose adjustments of cenobamate and concomitant ASMs were allowed. Total concomitant ASM drug load (not including cenobamate) was calculated by dividing the patient’s prescribed dose by its defined daily dose, a standardized daily maintenance dose provided by the World Health Organization, then summing the ratios. Changes in concomitant ASM drug load were measured from baseline in 3-month intervals and were assessed for up to 24 months by both total concomitant ASM drug load and class-specific ASM drug load (sodium channel blocker [SCB], synaptic vesicle protein 2A [SV2A], benzodiazepine [benzo], and other). Subgroups of interest included: older adults (65-70 years), prior epilepsy-related surgery vs nonsurgical, and baseline seizure frequency < 3 vs. ≥ 3 seizures/28 days. The impact of changes in drug load on efficacy maintenance was measured as percentage of patients who maintained ≥ 50% or 100% response rate between visits (3-month interval) with drug load reductions, compared to patients with no drug load reduction.

Results: Data from 240 patients were available (median duration of exposure, 30.2 months; mean age, 41.8 years). Total concomitant ASM drug load reductions began following cenobamate treatment initiation and decreased in the overall population and in all patient subsets (Table 1). Mean concomitant ASM drug load was reduced for all ASM drug classes (Figure), with the largest mean percent reduction in benzos (55.24% reduction at Month 24) which may be related to cenobamate’s drug-drug interaction with clobazam. All assessed patient subgroups exceeded 30% reduction in concomitant ASM drug load at Month 24 (Table). Patients with low (-0.25 to < 0), moderate (-0.59 to -0.25), or high (-3.3 to -0.59) change in concomitant ASM drug load vs. no change, respectively, had similar maintenance of ≥ 50% (89.29%, 86.42%, 90.57% vs. 85.99%) and 100% response rates (80.65%, 84.29%, 70.00% vs. 82.00%).