Abstracts

Rationale: Cenobamate is an antiseizure medication (ASM) approved in the US and EU for treatment of focal seizures in adults. Some ASMs are associated with weight gain, which can negatively affect patient health via cardiac disease, diabetes, high blood pressure and cholesterol, as well as quality of life and mental health. Further, weight gain is associated with reduced compliance. Some commonly used ASMs associated with weight gain are valproate, gabapentin, and pregabalin. Here, we report the effects of adjunctive cenobamate and concomitant ASMs on weight from two double-blind, placebo-controlled phase 2 studies (YKP3089C013 [C013] and YKP3089C017 [C017]) and their open-label extensions (OLE), and from a global, long-term, open-label phase 3 safety study, YKP3089C021 (C021).

Methods: Patients with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled in all 3 studies. In C013, cenobamate dosage began at 50 mg/day, increasing by 50 mg/day at 2-week intervals to a target dose of 200 mg/day (max OLE dose 400 mg/day). In C017, patients were randomized to cenobamate at 100, 200, or 400 mg/day. Dosage began at 50 mg/day, increasing weekly by 50 mg/day to 200 mg/day; patients assigned to 400 mg/day received further weekly increases of 100 mg/day to 400 mg/day (max OLE dose 400 mg/day). In C021, the currently recommended titration schedule was followed with an initial dose of 12.5 mg/day, increasing at 2-week intervals (25, 50, 100, 150, and 200 mg/day) to a target dose of 200 mg/day. The dose could then be increased by 50 mg/day every 2 weeks to a maximum of 400 mg/day. Median weight changes at 1 and 2 years from baseline for patients receiving adjunctive cenobamate and concomitant ASMs were analyzed post-hoc from each study. Median weight changes were further analyzed for subsets of patients who either continued or discontinued concomitant valproate, gabapentin, or pregabalin at 1 and 2 years from baseline.

Results: Weight data were analyzed in 39, 206, and 1054 patients from C013, C017, and C021, respectively. For the C017 study, weight data for the 100, 200, and 400 mg/day dose groups were combined. Median weight changes from baseline ranged from -0.2 to -0.9 kg and from baseline to 2 years ranged from -1.0 to +1.0 kg (Table). Some numerical reductions in weight were noted in patients who discontinued valproate by 1 (-13.0 kg, C013, n=1) or 2 years (-24.5 kg, C017, n=2) and in patients who discontinued gabapentin by 1 (-7.1 kg, C017, n=2) or 2 years (-7.0 kg, C017, n=2). Otherwise, median weight changes from baseline to 1 year for patients receiving concomitant valproate, gabapentin, or pregabalin ranged from -3.1 to +2.6 kg at 1 year and from -1.6 to +2.7 kg at 2 years.

Conclusions: This post-hoc analysis of clinical studies suggests that adjunctive cenobamate was not associated with clinically significant changes in weight from baseline in patients treated for 1 and 2 years, including those receiving concomitant valproate, gabapentin, or pregabalin.

Funding: Funded by SK Life Science, Inc.