Perampanel Effective, Well-Tolerated in Lennox-Gastaut Syndrome

Carlo Di Bonaventura, MD

Data from a recent study suggest that treatment with perampanel (Fycompa; Eisai) is safe and well-tolerated in patients with Lennox-Gastaut syndrome (LGS). Findings were presented at the 2021 American Epilepsy Society (AES) Annual Meeting, December 3-7 in Chicago and virtually. 

Following identification of 35 patients with LGS, a total of 33 were assessed for retention, 30 were assessed for effectiveness, and 22 were assessed for safety and tolerability of treatment with perampanel for focal-onset and/or generalized-onset seizures. Of the 30 patients who were assessed for effectiveness at the time of the last visit, 17 patients (56.7%) responded to treatment, defined as 50% or greater reduction in seizure frequency, and 1 patient (3.3%) reported seizure freedom, defined as no seizures since at least the prior visit. A total of 7 patients (23.3%) had unchanged seizure frequency and 2 patients (6.7%) experienced worsening seizure frequency.

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“Treatment of LGS is challenging due to the presence of multiple seizure types and comorbidities,” study investigator Carlo Di Bonaventura, MD, Department of Human Neurosciences, University di Roma Sapienza, and colleagues wrote.¹ “In this difficult-to-treat, small population of LGS patients, perampanel demonstrated effectiveness and was generally well tolerated when used in everyday clinical practice.”

At baseline, the mean perampanel dose was 2.0 mg/day (standard deviation [SD], 0.0) and 6.1 mg/day (SD, 2.8) at the last visit. Investigators observed retention rates of 90.9% (30/33) at 3 months, 75.8% (25/33) at 6 months, and 63.3% (19/30) at 12 months. 

The mean amount of time spent undergoing treatment with perampanel was 10.3 months (95% CI, 8.2-12.0). Patients most often discontinued treatment due to adverse events (AEs) (16.7%), lack of efficacy (13.3%), or a combination of AEs and lack of efficacy (6.7%). Among the 22 patients assessed for safety and tolerability, 15 (68.2%) experienced AEs and 7 (33.3%) experienced psychiatric AEs. Five patients (22.7%) reported irritability, 2 (9.1%) reported instability or ataxia, and 2 (9.1%) reported somnolence. 

Data from another recent study also suggest perampanel significantly reduces epileptic seizures, migraine attacks, and the use of monthly rescue migraine medications over a 12-month period in a cohort of patients with comorbid epilepsy and migraine. In the observational study, senior author Claudio Liguori, MD, neurologist, Epilepsy Center, University of Rome, and colleagues aimed to confirm the effectiveness of perampanel in 31 enrolled patients (mean age, 40.13 years; 67.7% women) with comorbid epilepsy and migraine.²

Fourteen patients (45.2%) started perampanel with 1 concomitant antiseizure medication (ASM) and 17 patients started the study drug in association with 2 ASMs (54.8%).

Most patients (n = 27; 87.1%) retained treatment at 12 months, with 2 patients discontinuing due to lack of efficacy and 2 due to AEs. Treatment with perampanel over the 12-month period resulted in seizure freedom for 11 patients, while 7 experienced at least 75% reductions, 3 with at least 50%, 1 with at least 25%, and 5 that remained unchanged. There was also a statistically significant difference in epileptic seizure frequency means across baseline and the 6- and 12-month follow-up visits (X² = 33.767; P <.001).

Perampanel also demonstrated a significant effect on migraine reduction, with 10 patients not experiencing a single migraine attack over the course of the 12-month period. Additionally, 7 participants reported at least 75% reduction in migraine attacks, 5 had reductions of at least 50%, 4 had a reduction of at least 25%, and 1 patient remained unchanged.

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REFERENCES

1. Bonnani P, Di Bonaventura C, D’Souza W, et al. Perampanel for treatment of patients with Lennox-Gastaut syndrome in clinical practice. Presented at AES 2021; December 3-7, 2021; Chicago, IL and Virtual. Abstract 2.107.
2. Fernandes M, Dono F, Dainese F, et al. Perampanel may represent an effective treatment for the prevention of migraine comorbid with epilepsy. Epilepsy Behav. Published online November 4, 2021. doi:10.1016/j.yebeh.2021.108391