Objective:

To examine the initial doses of cenobamate that were associated with seizure freedom (SF) in the phase 3 open-label efficacy subset.

Background:

Design/Methods:

Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications (ASMs) were administered cenobamate using the currently approved titration schedule. Post-hoc focal seizure data were available for 240 patients from 10 eligible US study sites.

Results:

Among the 240 patients, 62 (25.8%) had SF for ≥12 months at their last study visit. Of these 62 patients (median SF duration 25 months [range: 11.6-40.1 months]), 56.5% (35/62) started their seizure-free interval at cenobamate doses of 12.5 to 200 mg/d. The breakdown of cenobamate doses that patients were on at the start of their ≥12 seizure-free interval were 12.5 (n=10), 25 (n=2), 50 (n=3), 100 (n=3), 150 (n=9), 200 (n=8), 250 (n=3), 300 (n=7), 350 (n=4), and 400 (n=13) mg/d. Among the 42 patients who had <3 seizures per 28 days at baseline, 61.9% (26/42) started their ≥12-month seizure-free interval on cenobamate doses of 12.5 to 200 mg/d. Among the 20 patients who had ≥3 seizures per 28 days at baseline, 45.0% (9/20) started their ≥12-month seizure-free interval on cenobamate doses of 12.5 to 200 mg/d.

Conclusions:

Among the efficacy subset of patients in the open-label phase 3 study who achieved long-term SF for ≥12 months, the initial seizure-free interval occurred at a wide range of cenobamate doses. These data highlight the potential for flexible and individualized dosing with cenobamate. Further research would help determine if the wide range of dosing with cenobamate provides an advantage in achieving seizure reduction, particularly SF, over ASMs with a limited dosing range.