Efficacy and Safety of Perampanel Monotherapy in Patients Aged ≥12 to <18 Years with Newly Diagnosed/currently Untreated Recurrent Focal-onset Seizures (FOS): FREEDOM Study 342

Background: In the US, Japan, and Korea, perampanel is approved as monotherapy and adjunctive therapy for FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥4 years, and adjunctive treatment of generalized tonic-clonic seizures in patients aged ≥12 (≥7, Korea) years. Study 342 (FREEDOM; NCT03201900) was a multicenter, Phase III, open-label study of perampanel monotherapy in patients aged ≥12 years with newly diagnosed/currently untreated recurrent FOS, with/without FBTCS. We report long-term (52 weeks) efficacy/safety data from the FREEDOM Study in patients aged ≥12– <18 years.

Methods: During the Core Study (4-week Pretreatment; 32-week Treatment [6-week Titration; 26-week Maintenance]), patients received perampanel 4 mg/day. If a patient had a seizure, they could be up-titrated to 8 mg/day (4-week Titration; 26-week Maintenance). Patients could enter the Extension for an additional 26 weeks (total: 52 weeks). Study outcomes included median percent change in seizure frequency per 28 days, seizure-freedom rates, time to first seizure onset, time to withdrawal from the study from the first date of the Core Maintenance Period, and incidence of treatment-emergent adverse events (TEAEs).

Results: Overall, 7/89 patients who received ≥1 dose of study drug were aged ≥12– <18 years (4-mg group, n=4; 4- and/or 8-mg/day, n=3). All seven patients completed the Core Study and Extension Phase. The median (minimum, maximum) percent reduction in seizure frequency/28 days was 100.0% (52, 100) at the end of the Extension Phase. A total of 3/7 (42.9%) patients who entered the Extension from the 4-mg/day Treatment Phase and 5/7 (71.4%) patients who entered from the 4- and/or 8-mg/day Treatment Phase while seizure free had sustained seizure freedom for 52 weeks (Core plus Extension). In addition, 1/7 (14.3%) patients achieved seizure freedom during the Core Study (4-mg) but reported seizures during the Extension, and 1/7 (14.3%) patients did not achieve seizure freedom during the Core Study on 4- and/or 8-mg/day. Following 52 weeks of perampanel treatment, the probability of seizure onset rate was 57.1% (95% confidence interval [CI]: 26.6, 90.2) in patients who entered the Extension from the 4-mg/day Treatment Phase and 28.6% (95% CI: 8.0, 74.2) in patients who entered from the 4- and/or 8-mg/day Treatment Phase.

TEAEs occurred in 6/7 (85.7%) patients (Core/Extension) with no TEAEs considered related to perampanel treatment. No serious TEAEs occurred; only 1 (14.3%) patient required dose adjustment (reduction). The most common TEAEs were nasopharyngitis (n=4 [57.1%]), dizziness, and headache (both n=3 [42.9%]).

Conclusion: Results of FREEDOM Study 342 suggest seizure freedom can be sustained during long-term treatment with perampanel monotherapy in patients aged ≥12– <18 years with newly diagnosed/currently untreated recurrent FOS with/without FBTCS at doses as low as 4 mg/day. Perampanel was well tolerated and no unexpected TEAEs were reported.

Funding: Eisai Co., Ltd.