Efficacy and Safety of Perampanel as First or Only Adjunctive Therapy in Patients with Focal-onset Seizures (FOS) or Generalized Tonic-clonic Seizures (GTCS) in Studies 412, 501, 410, and 509
Abstract number :
2.121
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2022
Submission ID :
2204529
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:25 AM
Authors :
Anna Gentile, PhD – Eisai S.r.l., Epilepsy; Stefano Meletti, MD, PhD – University of Modena and Reggio Emilia; Vineet Punia, MD, MS – Charles Shor Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA; Ji Woong Lee, BPharm – Eisai Korea Inc., Seoul, Republic of Korea; Samantha Goldman, MD, B.Sc (Hons) – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Ricardo Sáinz-Fuertes, LMS, MSc, MRCPsych, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Tobias Goldmann, PhD – Eisai GmbH, Frankfurt am Main, Germany; Edgar Kockelmann, MD – Eisai GmbH, Frankfurt am Main, Germany; Bernhard Steinhoff, MD – Kork Epilepsy Center, Kehl-Kork, Germany
Rationale: Around 50% of patients achieve seizure freedom with their first anti-seizure medication (ASM). However, some patients will require an adjunctive ASM to achieve seizure control. Perampanel is a once-daily oral ASM for FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), and GTCS. We examine the efficacy and safety of perampanel as a first/only adjunctive ASM in patients in Studies 412 (NCT02726074; FAME; Korea), 501 (NCT04257604; AMPA; Italy), 410 (NCT03288129; ELEVATE; US), and 509 (NCT04202159; PERPRISE; Germany).
Methods: Patients in Studies 412 and 501 were aged ≥ 12 years with FOS, with/without FBTCS. Study 412 was a Phase IV open-label study of perampanel as first adjunctive ASM (≤ 12 mg/day; 36 weeks). Study 501 included patients prescribed perampanel (≤ 12 mg/day) during routine clinical care over 12 months. Study 410 was a Phase IV open-label study of monotherapy and first adjunctive perampanel in patients aged ≥ 4 years with FOS, with/without FBTCS, or GTCS (≤ 12 mg/day; up to 52 weeks). The Phase IV Study 509 evaluated perampanel as the only adjunctive ASM in adults (≥ 18 years) with FBTCS or GTCS with idiopathic generalized epilepsy during 12 months of clinical practice. Efficacy endpoints included median percent change in seizure frequency/28 days, 50% and 75% responder rates, seizure freedom, and retention rate (as available); safety endpoints included treatment-emergent adverse events (TEAEs). Only patients receiving perampanel as first adjunctive ASM (only adjunctive ASM in Study 509) were included in these analyses.
Results: In Study 412, 85 patients with FOS, including 16 with FBTCS, were included in the Full Analysis Set (FAS). The most common concomitant ASM was levetiracetam (n=34 [40.0%]). In Study 501, 8 patients who received perampanel as first adjunctive ASM were included in the FAS. The most common concomitant ASM was carbamazepine (n=5 [45.5%]). In Study 410, 44 patients received perampanel as first adjunctive ASM (FOS, n=30; GTCS, n=9; FOS+GTCS, n=5; FAS); levetiracetam was the most common ASM at baseline (n=24 [54.5%]). The Interim Analysis Set of Study 509 included 100 patients. The most common concomitant ASM was lamotrigine (n=35 [35.0%]). Efficacy data are shown in Table 1. Median reduction from baseline in seizure frequency/28 days ranged from 61.6% to 100.0% (various seizure types and time periods). The 50% and 75% responder rates were 62.5–87.5% and 25.0–87.5%, respectively, and seizure freedom rates were 12.5–75.0%. Retention rate at Month 6 was up to 78.0%. A summary of TEAEs is presented in Table 2.
Conclusions: Based on the available data from these studies, perampanel as a first or only adjunctive ASM was found to be efficacious and generally well tolerated. These data support the use of perampanel as an early-line treatment option for patients with various seizure types (FOS, FBTCS, and GTCS).
Funding: Eisai Korea Inc., Eisai S.r.l., Eisai Inc., Eisai GmbH
Clinical Epilepsy