Perampanel as Monotherapy or First Adjunctive Therapy Effectively Reduced Seizures in a Phase 4 Study

In the ELEVATE study (NCT03288129), 63% (34/54) of individuals, age 4 or more, who were treated with perampanel (Fycompa; Eisai, Woodcliff Lake, NJ) as monotherapy or a first adjunctive therapy continued treatment over a 12-month period. The retention rate was higher when perampanel was used as monotherapy vs first adjunctive therapy (80% vs 59%).

After titration from 2 mg/day to an effective dose (mean 6.4±2.1 mg/day), seizure frequency was reduced by 50% or more for 78.7% of the participants. Profound seizure reduction of 75% or more was seen in 55.3%, and seizure freedom was attained by 32.7% of participants. The mean length of treatment after titration was 39.8±20.0 weeks (range 1-65). Seizure reduction was observed in those with focal-onset seizures (FOS), with or without bilateral tonic-clonic seizures (FBTCS), as well as with generalized tonic-clonic seizures.

Perampanel treatment did not decrease quality of life for adult participants or subjective measures of sleep for participants over the age of 12. At the end of the study, the mean change in QoL for adults was +2.4±9.5 points measured on the Quality-of-Life Inventory in Epilepsy-31 (QOLIE-31; scale 1-100) on which a higher score equates to higher QoL. Changes in sleep quality were -0.2±3.9 points on the Pittsburgh Sleep Quality Index (PSQI; scale 1-21) on which lower numbers reflect better sleep quality. QoL and sleep were not evaluated in participants under age 12. Negative effects on cognitive functioning or depression also were not observed.

Treatment emergent adverse events (TEAEs) occurred in 88.9% of participants. The most common TEAEs were dizziness (27.8%) and fatigue (16.7%). There were 4 individuals who had serious TEAEs were including sudden unexpected death in epilepsy (SUDEP unrelated to perampanel; n=1), transient ischemic attack (n=1), depression and suicidal ideation (n=1), and mental status changes (n=1).  

In this study titration of perampanel from 2 mg/day to 4 mg/day occurred over a 3-week period. Additional dose escalation by 2 mg/day every 2 weeks up a maximum of 12 mg/day was permitted based on clinical response and tolerability. For individuals taking concomitant enzyme-inducing antiseizure medications, perampanel could be increased at 1-week intervals.