Efficacy and Safety of Adjunctive Perampanel in Indian Patients with Focal Seizures

2 Aug, 21

Introduction

There is a high prevalence of epilepsy in Asian countries including India. Unfortunately, the results of all clinical trials related to various antiepileptic drugs (AEDs) may not be applicable to Asian population owing to the differences in their genetic backgrounds. It is therefore critical to assess the efficacy and safety of various AEDs at the individual country level. Perampanel is approved as an adjunctive therapy for focal seizures (FS) in more than 55 countries, and for generalized tonic-clonic seizures (GTCS) in more than 50 countries. Currently, long-term data on the safety and efficacy of perampanel is lacking.

Aim

To assess the efficacy and safety of long-term adjunctive perampanel therapy in Indian patients

Patient Profile

Indian patients (aged ≥ 12 years) with FS, with/without FBTCS

Methods

Study Design

A post hoc analysis of six double- blind, randomized, Phase II and Phase III trials and their open-label extension (OLEx)
All the trials evaluated the efficacy and safety of adjunctive perampanel (2–12 mg/day) and recruited patients in India

Treatment Strategy

Participants from various double-blind trials were already receiving 1-3 AEDs and were further randomized to receive either placebo or adjunctive perampanel (2-12 mg/day). The treatment phase for the various trials included in this post hoc analysis ranged from 17-19 weeks
Patients in the OLEx studies received perampanel at a maximum dose of 12 mg/day and the exposure to perampanel ranged from 1-5 years.

Outcomes

Efficacy Outcomes

Median % change in seizure frequency per 28 days
50% and 75% responder rate (Proportion of patients with ≥50% or ≥75% reduction in seizure frequency per 28 days during the maintenance phase of the double-blind studies or each respective OLEs)
Seizure-freedom rate

Safety Outcomes

Treatment-emergent adverse events (TEAEs)

Results

The study population for the double-blind-Safety Analysis Set comprised of 128 patients (placebo, n=39; perampanel, n=89) and that for the Full Analysis Set comprised of 126 (FS, n=113 [placebo, n=32; perampanel, n=81]; FBTCS, n=35 [placebo, n=14; perampanel, n=21])
Indian patients treated with perampanel (4-12 mg/day) had a greater median percent reduction in seizure frequency per 28 days when compared with placebo, though the difference was statistically non-significant; (FS: 49.8% vs. 34.8% and FBTCS: 60.5% vs. 43.1%) at 4–12 mg/day, respectively. Similarly, perampanel (8 mg/day) was associated with a nonsignificant greater reduction in seizure frequency as compared with placebo.
The ≥ 50% responder rate with perampanel was non-significantly greater as compared with placebo for FS (55.1% vs. 37.5%) and FBTCS (60.0% vs. 42.9%). The ≥75% responder rate with perampanel treatment was significantly greater than placebo.
Higher proportion of patients treated with perampanel vs. placebo remained seizure-free (FDS: 5.8% vs. 0%; FBTCS: 10.0% vs. 7.1%), though the difference was insignificant.
The incidence of TEAE was similar in perampanel-treated and placebo-treated Indian patients (58.4% vs. 53.8%), and was lesser as compared with non-Indian patients.
The incidence of treatment-related TEAE was similar for perampanel-treated and placebo-treated Indian patients (39.3% vs. 38.5%) and was lesser than that seen in non-Indian patients (38.9% vs. 61.7%)
Overall, 110 patients entered OLEx studies and were included in the Full Analysis (FS, n = 99; GTCS, n = 11).
The seizure frequency for FS and FBTCS reduced during the long-term follow-up period in perampanel-treated Indian and non-Indian patients. The 50% and 75% responder rates were maintained for up to four years for FS and FBTCS. Seizure freedom was also maintained for up to four years FS and FBTCS.

Conclusions

Adjunctive treatment with perampanel as compared with placebo, was efficacious for up to four years in terms of greater reduction in frequency of FS and FBTCS, though the difference did not reach statistical significance.
Efficacy and safety outcomes for adjunctive perampanel treatment were generally similar for Indian and non-Indian patients.

Epilepsia Open. 2021;6:90–101.