Long-Term Seizure Freedom with Adjunctive Perampanel in Patients with Focal-Onset and Focal to Bilateral Tonic-Clonic Seizures: Post Hoc Analysis of Study 335 Open-Label Extension (OLEx)
Abstract number :
2.202
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825641
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Manoj Malhotra, MD - Eisai Inc.; Takuji Nishida, MD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Sang Kun Lee, MD, PhD – Seoul National University Hospital, Seoul, Republic of Korea; Yushi Inoue, MD, PhD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Kazunori Saeki – Eisai Co., Ltd.; Kohei Ishikawa, MSc – Eisai Co., Ltd.; Anna Patten, PhD – Eisai Europe Ltd.; Sunao Kaneko, MD, PhD – North Tohoku Epilepsy Center, Minato Hospital
Rationale: In the US/Japan, perampanel is approved for focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS; monotherapy/adjunctive), and generalized tonic-clonic seizures. Here, we report long-term seizure-freedom rates with adjunctive perampanel in patients (aged ≥ 12 years) from Asia-Pacific with refractory FOS, with/without FBTCS, who participated in Study 335 OLEx (NCT01618695).
Methods: Study 335 was a Phase III, multicenter, randomized, double-blind, placebo-controlled trial with an OLEx Phase. The Core Study comprised 6-week Prerandomization, 6-week Titration, and 13-week Maintenance Periods. The OLEx comprised 4-week Preconversion, 6-week Conversion, and at least 46-week Maintenance Periods. In this post hoc analysis, seizure-freedom rates for up to 12 months were assessed in perampanel-treated (4–12 mg/day) patients who achieved seizure freedom during the 13-week Core Study Maintenance Period to determine if their seizure-free status was maintained during the OLEx Phase. Additional analyses were also carried out to assess the number (proportion) of patients who achieved seizure freedom for a period of ≥ 6 and/or ≥ 12 consecutive months during the Core Study and/or OLEx Phase; some of these patients may have received placebo during the Core Study but only their time on perampanel is included in the seizure-free analysis. Treatment-emergent adverse events (TEAEs) across the entire study are also presented.
Results: Overall, 677/679 (99.7%) patients were enrolled and had seizure follow-up data recorded. A total of 599 patients completed the Core Study and 596 patients entered the OLEx; of these, 445 patients were randomized to perampanel and 151 to placebo during the Core Study. During the OLEx, 65.0% (n=13/20) and 45.0% (n=9/20) of patients who received perampanel and were free from all FOS during the Core Study Maintenance Period remained seizure free for 6 and 12 months, respectively (Figure 1A). For the subgroup of patients with FBTCS, 87.5% (n=35/40) and 55.0% (n=22/40) of patients who received perampanel and were free from FBTCS during the Core Study Maintenance Period, remained seizure free for 6 and 12 months, respectively (Figure 1A). Across the entire study (Core/OLEx), 8.0% (n=54/677; FOS) and 27.5% (n=64/233; FBTCS) of patients were seizure free for a period of ≥ 6 consecutive months, and 4.1% (n=28/677; FOS) and 14.2% (n=33/233; FBTCS) of patients were seizure free for a period of ≥ 12 consecutive months (Figure 1B). Perampanel was generally well tolerated. Table 1 shows an overview of TEAEs; the most common was dizziness. For both seizure types, 17.5% or fewer seizure-free patients discontinued perampanel due to TEAEs.
Conclusions: Seizure-freedom rates were sustained for up to 12 months and perampanel was generally well tolerated in patients aged ≥ 12 years from Asia-Pacific with refractory FOS, with/without FBTCS, suggesting perampanel may be a suitable long-term treatment option for these patients.
Funding: Please list any funding that was received in support of this abstract.: Eisai Co., Ltd.
Anti-seizure Medications