Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342)

FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12–74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS). In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed. In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-‍‍‍mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for > 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4–8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4–8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event. Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4–8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings. •Clinical outcomes of perampanel monotherapy 4–8 mg/day were studied for ≤ 104 weeks.•The 52-week seizure-freedom rate with perampanel was 42.5 % (n = 31/73) at 4–8 mg/day.•The risk of seizure recurrence within 52 weeks was 28.9 % with perampanel 4–8 mg/day.•No new safety concerns emerged over ≤ 104 weeks of perampanel monotherapy treatment.