Efficacy and safety of perampanel as first adjunctive therapy in patients with focal-onset seizures or generalized tonic-clonic seizures in four post-marketing studies across regions

Objective: Early response to anti-seizure medication (ASM) is associated with a favorable prognosis in patients with epilepsy. Research is required to confirm existing data on the clinical use of perampanel as first adjunctive therapy in different patient groups and different regions. Here, we present a post hoc analysis of four post-marketing studies to examine side by side the efficacy and safety of perampanel administered as the first adjunctive ASM across different geographic settings. Methods: Data from patients receiving first adjunctive perampanel were included in this post hoc analysis from Study 412 (NCT02726074, South Korea), Study 410 (NCT03288129, US), Study 509 (NCT04202159, Germany), and Study 501 (NCT04257604, Italy). Assessments included the median percent reduction from baseline/screening in seizure frequency, seizure-freedom rate, retention rate, and safety. Results: A total of 170 patients who received first adjunctive perampanel were included in this study, including 102 patients from Study 412, 44 from Study 410, 13 from Study 509, and 11 from Study 501. At the latest time point in each study, 50% responder rates were ≥62.5% (range, 62.5%–100.0%) across seizure types, while seizure-freedom rates ranged from 25.0% to 100.0% (median, 51.6%). Retention rates were ≥61.8% at Month 6 in all studies and ≥54.5% at Month 12 in Studies 410 and 501 where these data were available. Overall, 46.2%–90.9% of patients experienced ≥1 treatment-emergent adverse event (TEAE) and 13.7%–27.3% discontinued perampanel due to TEAE(s). The most common TEAEs reported across each study were dizziness (≤50.0%), somnolence (≤36.4%), and fatigue (≤13.6%). Significance: The results from this post hoc analysis demonstrated that perampanel as first adjunctive therapy had a good treatment response with no new safety signals observed. Limitations included the post hoc nature of the analysis and the inability to pool data due to study design differences. Overall, these data support the use of perampanel as an early-line treatment in patients with epilepsy. Plain Language Summary: This analysis looked at a medicine called perampanel and how well it works for people with epilepsy when it was one of the first medicines added to their regular seizure treatment. Data were collected from four separate studies that were done in South Korea, the United States, Germany, and Italy. Most patients had fewer seizures across all four studies after 6 months of treatment. The most common side effects reported in patients included dizziness and sleepiness. Perampanel worked well when used early during treatment, and most people were able to keep taking perampanel without significant difficulties.