Effectiveness and Safety of Perampanel in Refractory Focal Epilepsy: Real‐World Evidence From a Chinese Cohort

P41 – 2776: Efficacy and safety of perampanel as add-on treatment for focal refractory epilepsy in children with autism spectrum disorder

Perampanel (PER) is an antagonist of AMPA receptors that has been approved for adjunctive treatment of partial-onset seizures. To evaluate effectiveness and safety of PER as add-on treatment in patients with severely refractory focal epilepsy. PER was introduced as add-on treatment in 22 consecutive patients with drug-resistant focal epilepsy. PER was started with 2 mg/day at bedtime and was up-titrated by 2 mg/day every 2-4 weeks. All patients suffered from severely refractory focal epilepsy (86% took 2 or more AEDs prior PER initiation; 40% had been submitted to surgery or were surgery candidates; 7 had VNS). After 12 months since PER initiation, the retention rate was 54.5% and the responder rate was 27.2%, including 9.1% seizure-free patients. Mean PER dose in the responders was 8 mg/day (range 4-10). Most common side effects were tiredness, behavioral changes (primarily aggressivity), dizziness and were reported in 59.1% of patients, leading to PER discontinuation in 31.8% of subjects. PER as add-on treatment can achieve clinically meaningful improvement in patients suffering from severely refractory focal epilepses. Further studies are warranted to explore the tolerability profile, with particular focus on psychiatric adverse events.

This systematic review and meta-analysis aims to evaluate the effectiveness and safety of perampanel (PER) as adjunctive therapy in patients with Lennox-Gastaut Syndrome (LGS), focusing on seizure outcomes and adverse events (AEs). A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to June 2025. Clinical trials and observational studies assessing PER in LGS patients were included. Screening and data extraction were performed independently by two reviewers. Bias was assessed using RoB 2.0, ROBINS-I, and NOS tools. Meta-analyses were conducted using a random-effects model to estimate pooled incidence rates with 95% confidence intervals (CI). Heterogeneity was quantified using I2 and chi-square tests. Six studies involving 247 LGS patients were included. The pooled responder rate (≥ 50% seizure reduction) was 50.0% (95% CI: 32.1%-67.9%), while seizure freedom was achieved in 9.8% (95% CI: 6.7%-26.3%). Seizure aggravation occurred in 5.3% (95% CI: 1.4%-12.0%). Discontinuation due to lack of efficacy and safety concerns was reported in 21.9% (95% CI: 8.1%-35.6%) and 11.0% (95% CI: 5.8%-16.2%), respectively. Behavioral AEs included irritability (13.7%), aggression (11.4%), and general behavioral changes (24.7%). PER demonstrates notable efficacy in reducing seizures in LGS, with a responder rate of 50%. While complete seizure freedom remains infrequent overall, a nearly 10% seizure freedom rate is clinically meaningful in this challenging context. Behavioral AEs are common and led to discontinuation in over 10% of cases. PER may serve as a second- or third-line adjunctive therapy, warranting individualized risk-benefit evaluation and close monitoring.

Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics

L-Dopa represents the mainstay of therapy of Parkinson's disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly, there remains a need to explore novel treatment strategies to manage the signs and symptoms of the later disease stages. The aim of the study was to evaluate the efficacy and safety of adjunctive perampanel (PER) in patients with PD through a meta-analysis of existing trials. Randomized, placebo-controlled, double- or single-blind, add-on studies of PER in patients with PD were identified through a systematic literature search. The following outcomes were assessed: changes from baseline to final efficacy visit in total daily OFF time, activities of daily living during OFF time and motor function during ON time, incidence of adverse events (AEs), and treatment withdrawal. Four trials were included involving 2266 participants, 1449 and 817 for PER and placebo treatment groups, respectively. Four PER daily doses were tested, namely 0.5, 1, 2 and 4mg. There were no significant differences in any efficacy outcome between PER and placebo treated patients. The risk ratios (RRs) for AEs, severe AEs and treatment withdrawal were similar between placebo and PER at 0.5, 1 and 2mg; the 4mg daily dose was associated with an increased risk of AEs [RR 1.118 (1.047-1.193)], and withdrawal for AEs [RR 1.345 (1.034-1.749)] and for any reason [RR 1.197 (1.020-1.406)]. In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.

Background: Epilepsy is one of the most common neurological disorders. Existing antiseizure medications (ASMs) are still unable to control seizures in one-third of these patients, making the discovery of antiseizure therapies with novel mechanisms of action a necessity. Aim of the Study: This study aimed to determine the safety and efficacy of perampanel (PER) as an adjuvant treatment for children with drug-resistant focal-onset seizures with or without focal to bilateral tonic-clonic seizures. Patients and methods: This is a single-center retrospective study of 38 epileptic pediatric patients, aged 2 to 14, at King Faisal Specialist Hospital and Research Center whose seizures were pharmaco-resistant to more than two antiseizure medications and followed for at least three months after PER adjuvant therapy initiation. Efficacy was assessed by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and side effects were also reported. Results: Multiple seizure types were reported. Myoclonic seizures were the predominant type of epilepsy in 17 children (44.7%). At 3 months, 6 months, and 12 months of follow-up, approximately 23.4%, 23.4%, and 18.4% of the patients were seizure-free at these time points, respectively. Adverse events were documented in 14 patients (35.7%) and led to the discontinuation of PER in 26.3%, 31.6%, and 36.8% of the studied group at the 3-, 6-, and 12-month follow-ups, respectively. The most common adverse events included dizziness or drowsiness, irritability, gait disturbance, and confusion; however, all were transient, and no serious adverse effects occurred. Conclusion: Our findings confirm the therapeutic efficacy of adjunctive PER in the treatment of drug-resistant epilepsy in children. As an adjunctive treatment for epilepsy, perampanel demonstrated sufficient effectiveness and tolerability.

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE).Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups.Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children’s Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%–87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups.Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE.Clinical Trial Registration: Identifier ChiCTR2300074696

Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy

Efficacy and safety of perampanel in genetic generalized epilepsy: A retrospective, single-center study in China.

Summary Introduction. Perampanel (PER) (Fycompa) 5′-(2-cyanophenyl)-1′-phenyl-2,3′-bipyridinyl-6′(1′H)-on is the newest antiepileptic drug and is the first-in-class selective non-competitive antagonist of ionotropic AMPA glutamate receptors of the postsynaptic neuronal membrane. The aim was to summarize Russian experience in using PER in daily clinical practice, and for this purpose the results of its use as an add-on treatment for focal epilepsy were assessed retrospectively Material and Method. The results of the study of PER efficacy and safety in 52 patients with refractory focal epilepsy are presented. Mean age was 28.9 ± 14.0 years; proportion of male patients was 56%, duration of the disease over 10 years - 69.2%, symptomatic epilepsy - 76.9%, with frontal - 46.2% and temporal - 44.2% localization of epileptic lesion. Majority of patients - 71.2% started PER treatment after 3 preceding lines of therapy Results. The baseline seizure frequency of all types was 127.3 ± 82.3 per month; secondary generalized seizures - 6.7 ± 1.9 per month. After PER was added, a significant decrease in seizure frequency was observed already during the first month, to 52.1 ± 29.3 seizures per month (Sign test, p = 0.00001) for seizures of all types and to 3.7 ± 1.7 (Sign test, p = 0.00001) for secondary generalized seizures. In an overwhelming majority of cases, duration of PER treatment was more than 6 months. In 58% of patients, seizure frequency decreased by more than 50% (responders). Seizure-free status for all seizure types was observed in 9% of cases at 12 month, and absence of secondary generalized seizures only was achieved in 31% of patients. Adverse events were observed in 30.1% of patients: aggression - 11.5% and drowsiness - 9.6%, with all other AEs observed more rarely. PER dose was reduced due to side effects in 7 patients (13.5%), and in 4 patients (7.7%) PER was discontinued. Average PER dose in adult patients was as low as 6 mg. Conclusions. PER was effective in the treatment of refractory forms of focal epilepsy, reducing seizure frequency on average by 76% by the second month of treatment. In addition to a good clinical effect, PER demonstrated a rather acceptable and predictable safety profile.

Perampanel (PER) is used less extensively in children than in adults. Currently, there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy, especially those with refractory epilepsy. To evaluate the effectiveness, retention, and safety of PER in the treatment of children and adolescents with epilepsy in China. This was a multicenter, prospective, observational study. Children and adolescents with epilepsy who received PER as adjunctive therapy were included. The primary effectiveness endpoint was the proportion of patients achieving a ≥50% reduction in seizure frequency after 6 months of treatment compared to baseline. The secondary effectiveness endpoints included retention and seizure-free rates. The safety outcome was the incidence of treatment-emergent adverse events (TEAEs). A total of 240 patients with epilepsy were enrolled in the study. Prior to initiating PER treatment, approximately 87.9% of them took two or more antiseizure medications. After a 6-month treatment regimen with PER, 70.4% of the patients experienced a reduced seizure frequency of at least 50%, and 22.1% achieved complete seizure freedom. The retention rate was 90.2%. TEAEs were reported by 89 patients, leading to the discontinuation of PER in seven cases. No severe TEAEs were observed in this study. Under routine clinical conditions, PER demonstrated good effectiveness and retention in Chinese children with epilepsy, particularly in those with refractory epilepsy.

Safety and Efficacy of Perampanel as Adjunctive Therapy in Patients with Refractory Focal Epilepsy Over 12 Months: Clinical Experience in a Real-World Setting

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study

Improved irritability, mood, and quality of life following introduction of perampanel as late adjunctive treatment for epilepsy

Peginterferon-α-2a (40KD) and Ribavirin for 16 or 24 Weeks in Patients With Genotype 2 or 3 Chronic Hepatitis C