Perampanel Safety, Efficacy, and Predictors of Major Response
Perampanel (FYCOMPA; Eisai, Woodcliff Lake, NJ) is approved for use as monotherapy for treatment of partial
-onset seizures (POS) with or without secondarily generalized seizures (SGS) and as adjunctive therapy of POS or primary generalized tonic-clonic seizures (PGTCS) in patients with epilepsy who are age 12 and over. A request for approval for using perampanel to treat the same indications in children age 2 to 12 has been filed based on earlier findings that pharmacokinetics for perampanel in children doesn’t differ from that in adults. Studies have been ongoing to assess safety and efficacy, patient retention, dosing experience, clinical factors related to efficacy, and the use of perampanel with a range of other antiepileptic drugs (AEDs). Results were presented at the American Academy of Neurology meeting this week.
In a post hoc univariate and multivariate analysis, the presence of SGS prior to initiating treatment with perampanel was the biggest predictive factor for achieving a major response to treatment, defined as a ≥75% reduction from baseline seizure frequency per 28 days. The 175 patients (12.7% of total subjects in phase 3 trials) who had a major response were more likely to have SGS before treatment.
Efficacy was measured specifically for adolescents, age 2 to 17 who were in phase 2 and phase 3 trials and continued on perampanel after a 6-week blinded conversion period, during which perampanel dose was optimized (≤12 mg/day). These patients then continued an open-label extension trial for 27 to 256 weeks (≤1 to ≤5 years’ exposure). At the 1-year point, patients had a median reduction of 62.8% in seizures per 28 days for patients with SGS and a 84% reduction in seizures per 28 days for patients with PGTCS.
In an interim analysis of an ongoing phase 4 retrospective study, more than half of patients who began taking perampanel were still doing so 24 months later (n = 187); 84.9% and 58.5% of patients continued treatment with perampanel at 3 and 24 months respectively. The most frequent reasons for discontinuing perampanel were adverse events (25%) or inadequate therapeutic responses (10%). The mean (range) maximum perampanel dose was 7.1 (1.5-20.0) mg, and the mean cumulative duration of exposure to perampanel was 15.4 months.
The effect of common concomitant AEDs on discontinuation and adverse events were also reported in a post hoc analysis of the open-label extension trial for PGTCS. The most commonly concomitant AEDs were valproic acid (n = 55), lamotrigine (n = 53), levetiracetam (n = 37), topiramate (n = 21), and zonisamide (n = 12). Some patients took more than 1 of the concomitant drugs while taking perampanel. The most common reasons for discontinuing perampanel were adverse event(s) (AE), patient choice, and ‘other.’ The primary reasons for discontinuation and the incidence of adverse events differed among the most common concomitant AEDs, although the types of adverse events were similar.
Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer of Eisai’s Neurology Group stated, “At Eisai, we are always exploring new solutions for those living with epilepsy including ways that FYCOMPA may help patients across the age spectrum. We are committed to helping patients achieve seizure-freedom and live their lives to the fullest. The data, including the real-world evidence, presented at AAN brings us closer to unlocking answers to make that possible.”