Perampanel Further Demonstrates Efficacy, Safety in Large Real-World Analysis

Adam Strzelczyk, MD

A pooled analysis of 44 real-world studies and work groups that included more than 5000 patients confirmed the safety and effectiveness of perampanel (Fycompa; Eisai), an FDA-approved antiseizure medication (ASM), in treating focal-onset and generalized-onset seizures in adult patients in the clinical setting.

Presented at the American Epilepsy Society (AES) Annual Meeting, December 3-7, 2021, the research assessed seizure freedom rate and responder rate, indicated by at least 50% reduction in seizure frequency, along with tolerability through adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation. Retention rate was evaluation at 3, 6, and 12 months. At baseline, the mean perampanel dosage was 2.3 mg/day (standard deviation [SD], 1.0) and increased to 6.4 mg/day (SD, 2.6) at the last visit.

Led by Adam Strzelczyk, MD, Department of Neurology, Goethe University, the analysis focused on those between ages 18 and 65 years and mainly comprised of those with focal-onset seizures (83.1%), followed by generalized-onset seizures (12.4%) and those with both focal and generalized-onset seizures (4.5%). Most of the patients were either on 2 or 3 concomitant ASMs at the initiation of perampanel therapy, with only 3.5% initiating it as a monotherapy.

A total of 3644 and 3817 patients, respectively, made up the efficacy and safety analysis populations. At the conclusion of the 12-month period, 52% of patients with generalized-onset seizures achieved seizure freedom, which was defined as no reported seizures since last visit. In the same group, 73.3% reported at least a 50% reduction in seizure frequency from baseline. For patients with focal-onset seizures, 14.5% demonstrated complete seizure freedom, whereas 44.6% of the group had at least a 50% response to treatment with perampanel.

In total, 50.7% of patients reported an AE, with dizziness/vertigo (16%) the most observed, followed by somnolence (10.7%), irritability (8.3%), behavioral disorders (5.1%), and instability/ataxia (4.1%). Throughout the study, 597 patients (16.8%) had AEs that led to discontinuation and 337 (9.4%) had psychiatric AEs leading to discontinuation. The most frequently reported psychiatric AEs leading to discontinuation included irritability (n = 114; 3.2%), behavioral disorders (n = 93; 2.6%), and mood disturbance (n = 48; 1.3%).

At the 3-, 6-, and 12-month time points, retention rates were 90.9% (3593 of 3954), 80.1% (3023 of 3775) and 64.8% (2302 of 3554), respectively. Investigators observed a mean retention time of 10.8 months, with 35.2% of patients discontinuing treatment throughout the trial. Of them, 8.8% were due to lack of efficacy, 14% due to AEs and 2.8% due to lack of efficacy and AEs.

Perampanel was initially approved in 2012 as an adjunctive therapy for partial-onset seizures (POS), and the indication was later expanded to include patients 12 years of age or older with primary generalized tonic-clonic seizures. In 2017, perampanel received a monotherapy indication for POS with or without secondary generalized seizures (SGS) in those with epilepsy 12 years of age and older. The FDA then expanded the indication of perampanel for monotherapy and adjunctive use in pediatric patients 4 years of age and older for the treatment of POS with or without SGS in September 2018. Notably, the approval included both tablet and oral suspension formulations.

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REFERENCES

Strzelcyk A, Wehner T, Deleo F, et al. Pooled analysis of adult epilepsy patients treated with perampanel in everyday clinical practice. Presented at AES Annual Meeting; December 3-7, 2021; Abstract V.052