(335) Efficacy of Cenobamate by Concomitant Antiseizure Medications in Patients With Uncontrolled Focal Seizures: Post-hoc Analysis of a Phase 3, Multicenter, Open-Label Study
Director Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA Bethesda, Maryland
Rationale: Cenobamate is an antiseizure medication (ASM) approved in the U.S. for the treatment of adults with focal seizures. Here, we report post-hoc efficacy of cenobamate by concomitant ASMs from ten U.S. study sites from an ongoing, global, open-label, Phase 3 safety study. Methods: Patients 18-70 years old with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled. Increasing daily doses of cenobamate were administered (12.5, 25, 50, 100, 150, and 200 mg/day) at two-week intervals. Further increases to 400 mg/day, using 50-mg/day increments every other week, were allowed. Patient visits occurred every two weeks for 16 weeks and then every one to three months. Results: Data were available for 249 patients; 183 (73.5%) were still receiving cenobamate (mean duration 33.9 months). Of 183 patients still on cenobamate, 62 (33.9%) were seizure-free for ≥12 months at last visit. Among the 62 patients, the most common concomitant ASMs were lacosamide and levetiracetam (41.9%, each), lamotrigine (27.4%), and zonisamide (22.6%). Combinations including lacosamide/levetiracetam were taken by 14.5% of the 62 patients, lamotrigine/levetiracetam by 8.1%, zonisamide/levetiracetam by 6.4%, lacosamide/lamotrigine by 4.8%, zonisamide/lacosamide by 4.8%, and zonisamide/lamotrigine by 4.8%. Responder rates (≥50%, ≥75%, 100%) were evaluated in 173/183 patients still on cenobamate (Figure 1). Excluded patients generally had < 1 focal to bilateral tonic-clonic seizure/year or missing data. Among the 173 patients, cumulative seizures decreased from 1823 at screening to 416 (77% decrease) during the last three months. The following three groups were analyzed relative to baseline ASM use: 1) patients still on cenobamate (n=183), 2) patients who discontinued cenobamate (n=66), and 3) patients seizure-free for ≥12 months (n=62) (Figure 2). A slightly greater percent of seizure-free patients took levetiracetam and zonisamide with cenobamate compared with other outcome groups. Slightly fewer patients remained on lacosamide and zonisamide in the group that discontinued cenobamate. The percent of patients taking lamotrigine remained stable across outcomes. The most common adverse events (AEs) when taking cenobamate with concomitant ASMs were dizziness, unsteadiness for lacosamide; dizziness, diplopia, sleepiness for lamotrigine; sleepiness, fatigue, somnolence, irritability for levetiracetam; and sleepiness, fatigue for zonisamide. Conclusions: Cenobamate was associated with clinically relevant seizure reduction when combined with commonly used ASMs. Relevant clinical outcomes were generally consistent by baseline ASM. The AE profile of the combinations was consistent with the known profiles of these ASMs, and no new tolerability issues were identified. Funding: Please list any funding that was received in support of this abstract.:
