Perampanel Reports High Compliance and Good Tolerance in Phase 4

Vineet Punia, MD, MS

Data from the phase 4 ELEVATE study (Study 410; NCT03288129) presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, demonstrated that patients were compliant with perampanel (Fycompa; Eisai) treatment and that the therapy was well tolerated.¹

The data, presented by Vineet Punia, MD, MS, neurologist, Cleveland Clinic, showed that patients were compliant with using perampanel as monotherapy or as the first adjunctive treatment for partial onset seizures (POS), secondarily generalized seizures (SGS), or primary generalized tonic-clonic seizures (PGTCS). (editor’s note: PGTCS seizures are now officially referred to as genetic generalized tonic-clonic seizures.)

Punia and colleagues note that the ongoing 12-month, multicenter, open-label, phase 4 study is the first prospective study of perampanel administered as monotherapy or first adjunctive therapy in patients aged ≥4 years with POS, with or without SGS or PGTCS. Data from 13 patients were presented, 10 with POS, 1 with SGS, and 3 with PGTCS. The mean age of patients was 45.2 years (standard deviation, 14.2). Perampanel was used as a monotherapy in 4 patients and as the first adjunctive therapy in 9. None converted to monotherapy during the trial.

Compliance was high, with 69.2% (n = 9) of patients having compliance rates of >90%, 7.7% (n = 1) with rates ≥80% but <90%, and 23.1% (n = 3) with rates ≥70% but <80%. Mean compliance was 93.2% (SD, 12.5) in the total patient population. 

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Researchers gave 2 mg/day doses of perampanel that were in some cases uptitrated to 4 mg/day based on clinical response and tolerability. Patients were permitted to receive ≤12 mg/day depending on their need for additional efficacy (titration: 2-mg/day increments at a minimum of 2-week intervals). One patient used enzyme-inducing anti-seizure medications (ASMs) and was permitted to be uptitrated in 2-mg/day increments at 1-week intervals. The primary end point was retention rate at 3, 6, 9, and 12 months, and the secondary end points were safety and seizure freedom.

The last dose of perampanel received was 4 mg (n = 3), 6 mg (n = 2), 8 mg (n = 6), 10 mg (n = 1) and 12 mg (n = 1). Treatment emergent adverse events (TEAEs) occurred in 84.6% (n = 11) of patients, though no patients withdrew from the trial.

Additional data presented at AES 2020 by Ji-Woong Lee, BS, MS, PhD, assistant professor, University of Copenhagen, and colleagues included multivariate analyses on the FAME study (Study 412; NCT02726074) that found that longer total administration period, higher perampanel dose, and presence of a concomitant non-ASM were potential predictors of response to perampanel. Concomitant non-antiepileptic medication was also a significant predictor of seizure freedom (P = .0421). No epilepsy-specific or demographic variables were found to predict seizure reduction.²

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REFERENCES
1. Punia V, Klein P, Kumar D, Salah A, Malhotra M. ELEVATE study 410 initial results: Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥4 years with partial-onset or primary generalized tonic-clonic seizures. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 766.
2.Lee JW, Kim DW, Seo DW, Dash A, Malhotra M. Clinical factors associated with response to perampanel as first adjunctive treatment in patients with partial-onset seizures in the FAME study. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 769.