Long-Term Efficacy and Safety of Perampanel Monotherapy in Patients with Newly Diagnosed/Currently Untreated Recurrent Focal-Onset Seizures (FOS): FREEDOM Study 342 Extension Phase
Abstract number :
1.283
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825615
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Takamichi Yamamoto, MD, PhD - Seirei Hamamatsu General Hospital; Sung Chul Lim, MD, PhD, – The Catholic University of Korea, St. Vincent’s Hospital; Hirotomo Ninomiya, MD – Itami City Hospital; Yuichi Kubota, MD – Tokyo Women’s Medical University Medical Center East; Won Chul Shin, MD, PhD – Kyung Hee University Hospital at Gangdong; Dong Wook Kim, MD – Konkuk University School of Medicine; Dong Jin Shin, MD, PhD – Gachon University Gil Medical Center; Tohru Hoshida, MD – Takanohara Central Hospital; Koji Iida, MD, PhD, – Hiroshima University; Taku Ochiai, MD, PhD, – Ochiai Neurological Clinic; Risa Matsunaga, N/A – Eisai Co., Ltd.; Hidetaka Hiramatsu, N/A – Eisai Co., Ltd.; Ji Hyun Kim, MD, PhD – Korea University Guro Hospital
Rationale: 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. Findings from the 342 Core Study (FREEDOM; NCT03201900) showed that 26 weeks’ maintenance therapy with perampanel 4–8 mg/day monotherapy was efficacious and well tolerated in patients aged ≥ 12 years from Japan/Korea with newly diagnosed/currently untreated recurrent FOS, with/without FBTCS. We report long-term (52 weeks) efficacy and safety data from the Extension Phase of FREEDOM.
Methods: During the Core Study, patients received perampanel 4 mg/day (4-week Pretreatment; 32-week Treatment [6-week Titration; 26-week Maintenance]). 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). 52-week seizure-freedom rates, time to first seizure onset/withdrawal from the study from the first date of the Maintenance Period, and treatment-emergent adverse events (TEAEs) (Core/Extension) were assessed; seizure-freedom rates beyond 52 weeks will be available for inclusion in the presentation.
Results: Overall, 89 patients received ≥ 1 perampanel dose (Safety Analysis Set). Of these, 73 patients entered the 4-mg/day Maintenance Period (modified Intent-to-Treat [mITT] Analysis Set); 21 patients had a seizure so entered the 8-mg/day Treatment Phase. Overall, 68.7% (n=46/67) of eligible patients entered the Extension (39 who completed the 4- [n=32] or 8-mg/day [n=7] Treatment Phases and 7 who discontinued the 8-mg/day Treatment Phase); 38 patients completed the Extension and 8 discontinued, most commonly due to withdrawal of consent (n=3 [6.5%]). Median (range) duration of perampanel exposure was 44.1 (1.1–142.3) weeks; mean (standard deviation) daily permapanel dose was 4.2 (1.3) mg/day (Core/Extension). Overall, 24/32 (75.0%) patients who entered the Extension from the 4-mg/day Treatment Phase and 31/39 (79.5%) patients who entered from the 4- and/or 8-mg/day Treatment Phase while seizure free had sustained seizure freedom for 52 weeks (Core Study plus Extension). Cumulative probability of seizure onset rate and rate of withdrawal are shown in Figure 1. TEAEs occurred in 74/89 (83.1%) patients (Core/Extension). An overview of TEAEs is shown in Table 1; the most common was dizziness (38.2%).
Conclusions: Final results of FREEDOM suggest seizure freedom can be sustained during long-term (52 weeks) treatment with perampanel monotherapy at doses as low as 4mg/day in patients with newly diagnosed/currently untreated recurrent FOS with/without FBTCS. Perampanel was well tolerated and no new TEAEs were reported.
Funding: Please list any funding that was received in support of this abstract.: Eisai Co., Ltd.
Anti-seizure Medications