Efficacy and Safety of Perampanel in Asian Patients: Evaluating Data from Five Phase III or IV Studies
Abstract number :
V.066
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825644
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Amitabh Dash, PhD - Eisai Singapore Pte., Ltd., Singapore; Hiroo Omatsu, MD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Takamichi Yamamoto, MD, MS, DMSc, FAES – Seirei Hamamatsu General Hospital; Sunao Kaneko, MD, PhD – North Tohoku Epilepsy Center, Minato Hospital, Hachinohe, Japan; Dong Wook Kim, MD – Konkuk University School of Medicine; Anshu Rohatgi, MD – Sir Ganga Ram Hospital; Rahul Kulkarni, MD, DM, DNB – Deenanath Mangeshkar Hospital and Research Center; Ji Woong Lee, BPharma – Eisai Korea Inc.; Balaji Patil, MD – Eisai Pharmaceuticals India Pvt., Ltd.; Anna Patten, PhD – Eisai Europe Ltd.; Leock Y. Ngo, PhD – Eisai Inc.; Manoj Malhotra, MD – Eisai Inc.
Rationale: Perampanel is a once-daily oral anti-seizure medication (ASM) for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCS). Reducing the treatment gap for epilepsy is a key challenge in Asia. This may be improved through better choice and availability of effective ASMs. Here, we report data from five clinical studies of perampanel in Asian patients.
Methods: Data were derived from 1135 Asian patients with FOS or GTCS who received perampanel in three Phase III studies with open-label extensions (Study 311 [Japan/Korea from global study; NCT02849626]; Study 335 [Asia-Pacific; NCT01618695]; Study 342 [Japan/Korea; NCT03201900]) and two Phase IV studies (Study 412 [Korea; NCT02726074]; Study 508 [India; NCT03836924]). Studies were single-arm and open-label except Study 335 (double-blind, placebo-controlled), and in patients aged ≥ 12 years except Study 311 (aged 4 to < 12 years). Patients received perampanel (2–12 mg/day) as adjunctive therapy (Studies 311, 335, 508); first add-on therapy (Study 412); or monotherapy (Study 342). Efficacy outcomes included percent change in seizure frequency/28 days and seizure-freedom rates; treatment-emergent adverse events (TEAEs) and tolerability were also assessed.
Results: Perampanel (adjunctive/first add-on/monotherapy) reduced seizure frequency in all Phase III and real-world studies; efficacy data are summarized in Table 1. In Study 311, the median percent reduction in seizure frequency/28 days at 13 and 52 weeks was 36.6% (n=66) and 58.9% (n=51), respectively. The seizure-freedom rate at 13 and 52 weeks was 4.5% and 5.9%, respectively. In Study 335, the median percent reduction in seizure frequency/28 days at 19 and 55 weeks was 26.6% (n=529) and 53.9% (n=338), respectively. Seizure-freedom rates at 19 weeks ranged from 2.9% to 4.4% across dose cohorts. In Study 342, seizure-freedom rate at 26 weeks was 63.0% (n=46/73) with 4 mg/day; 24/32 (75.0%) patients who entered the OLEx on 4 mg/day remained seizure free for 52 weeks. In real-world studies 412 and 508, seizure freedom was achieved by almost 50% of patients after 6–9 months of adjunctive perampanel. In Study 412, median reduction in seizure frequency/28 days was 95.0% (n=84) at Week 36 and the seizure-freedom rate was 47.1%. In Study 508, reduction in seizure frequency/28 days at 6 months was 100.0% (n=174) and the seizure-freedom rate was 49.4%. Assessed over a mean perampanel exposure period of up to 98 weeks, most TEAEs were mild to moderate in severity, with generally low rates of serious TEAEs and withdrawals due to TEAEs (Table 2). Consistent across studies, the most common TEAEs included dizziness, nasopharyngitis, somnolence, and headache.
Conclusions: Treatment with perampanel as monotherapy, first add-on, or adjunctive therapy resulted in improved seizure control in all Asian subgroups across a variety of settings and at doses as low as 4 mg/day. Perampanel was safe and well tolerated in this subpopulation. These data are consistent with those from the overall populations.
Funding: Please list any funding that was received in support of this abstract.: Eisai Inc., Eisai Co., Ltd., Eisai Korea Inc., and Eisai India Pvt. Ltd.
Anti-seizure Medications