A Phase 4, multicenter, prospective, non-interventional, observational study to investigate the effectiveness and safety/tolerability of perampanel when used as first adjunctive therapy in routine clinical practice in people with epilepsy: Study 512

Sergey Burd ^1,2* Giovanni Assenza ^3,4 Sofia Mendes Quintas ⁵ Francisco José Gil López ⁶ Jan Wagner ⁷ Anna Lebedeva ^1,2 Pavel Vlasov ⁸ Nina Pantina ² Anna Patten ⁹ Samantha Goldman ⁹ Ricardo Sáinz-Fuertes ⁹ Marta Torres Arlandis ⁹ Stanislas Lagarde ^10,11 Tobias Sejbaek ^12,13 Vadim Kharkovsky ⁸

• ¹ Pirogov Russian National Research Medical University, Moscow, Russia
• ² Federal Center of Brain Research and Neurotechnologies, Moscow, Moscow Oblast, Russia
• ³ UOC Neurologia, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
• ⁴ Research Unit of Neurology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
• ⁵ Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
• ⁶ Hospital Universitari del Sagrat Cor, Barcelona, Spain
• ⁷ University of Ulm and Universitäts-und RehabilitationsklinikenUlm, Ulm, Germany
• ⁸ Department of Neurology, Scientific Research Institute of Clinical Medicine named after N.A. Semashko, Russian University of Medicine, Moscow, Russia
• ⁹ Eisai Europe Ltd, Hatfield, United Kingdom
• ¹⁰ APHM, Timone Hospital, Epileptology and Cerebral Rhythmology, Marseille, France
• ¹¹ Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France
• ¹² Hospital Southwest Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
• ¹³ University of Southern Denmark, Odense, Denmark

Introduction: Study 512 aimed to assess the efficacy and safety of perampanel (PER) as first add-on therapy. Methods: In this 12-month, prospective, observational, multicenter study, people with epilepsy (PWE) aged ≥12 years with focal-onset seizures or generalized tonic-clonic seizures (GTCS) associated with idiopathic generalized epilepsy received PER as first add-on therapy to antiseizure medication (ASM) monotherapy. The primary efficacy endpoint was retention rate at 12 months. Other endpoints included change in seizure frequency from baseline; pragmatic seizure freedom rate (proportion of PWE in the full analysis set achieving freedom from all seizures); responder rate (≥50% seizure frequency reduction from baseline), changes from baseline in the 10-item Quality of Life in Epilepsy questionnaire (QOLIE-10) total score, the Epworth Sleepiness Scale (ESS) and the age-corrected EpiTrack and EpiTrack Junior total score; safety/tolerability (treatment-emergent adverse events [TEAEs]); and PER dose. Results: Of 184 PWE (Safety Set, n=182; Full Analysis Set, n= 174;), 135 (73.4%) completed the 12-month study. Mean PER dose was 4.7 mg/day. Retention rate at 12 months was 74.2% in the overall population, 81.8% in the 12 to <18 years age group, 74.3% in the 18 to <65 years age group, and 66.7% in the ≥65 years age group. Retention rates were similar between PWE with focal-onset seizures (74.5%) and GTCS (75.0%). Median reduction in monthly seizure frequency per 28 days from baseline to 12 months was 78.6% in the overall population, 92.3% in the 12 to <18 age group, 75.0% in the 18 to <65 years age group, and 87.5% in the ≥65 years age group. In the overall population, pragmatic seizure freedom rates at 12 months were 36.2% (all seizures), 34.1% (all focal seizures) and 45.5% (GTCS); responder rate at 12 months was 64.4% in the overall population. In total, 52.7% of PWE experienced TEAEs and 12.1% discontinued due to TEAEs. No significant changes were identified from baseline to 12 months in QOLIE-10, ESS and the age-corrected EpiTrack and EpiTrack Junior scores. Conclusion: PER was efficacious for focal and generalized seizures across all age groups and was generally well-tolerated, as demonstrated by the high retention rates at 12 months