Abstracts

Rationale: LGS is a severe refractory childhood-onset epilepsy characterized by triad of multiple seizure types (including drop seizures), intellectual disability, and certain electroencephalographic abnormalities. Here, we report changes in symptoms from baseline during the Core Study of Study 338 (NCT02834793; Phase III) using the CGI scale in patients aged ≥ 2 years with uncontrolled seizures with LGS.

Methods: Study 338 enrolled patients with clinical and electroencephalogram confirmation of LGS diagnosis with disease onset before 11 years of age, who were receiving 1–4 concomitant anti-seizure medications at stable doses for ≥ 30 days before screening and had an average of ≥ 2 drop seizures/week during baseline. The Core Study was a randomized, double-blind, placebo-controlled phase (4–8-week screening/baseline, 6-week Titration [2 to ≤ 8 mg/day based on response and tolerability], 12-week Maintenance). In addition to seizure response, treatment effect of perampanel was assessed by changes in CGI scores (CGI-C; rated on a 7-point scale based on the physician’s assessment vs baseline severity). Results were stratified by age (children, adolescents, and adults). Patients showing ‘minimally improved/worse’ and ‘no change’ were classified as no changes in symptoms. The ‘much/very much improved’ categories were classified as improvement in symptoms, and similar classification was used to define worsening.

Results: Seventy patients were randomized in the Core Study to receive either perampanel (n=34) or placebo (n=36). Overall, at Week 18, the majority of patients showed no changes in symptoms, irrespective of treatment (65.6% [perampanel] vs 88.6% [placebo]; Figure 1A). The proportion of patients showing an improvement in symptoms was numerically greater with perampanel (25.0%) vs placebo (8.6%); a similar trend was observed with worsening (9.4% [perampanel] vs 2.9% [placebo]; ‘very much worse’, n=0 each). When stratified by age, similar trends of CGI-C were observed among children and adult patient cohorts (Figures 1B and 1D). Among children, 62.5% (perampanel) and 77.8% (placebo) of patients showed no changes; 31.3% of patients showed improvement with perampanel vs 16.7% (placebo); 6.3% of patients showed worsening with perampanel vs 5.6% (placebo). For adult patients, 58.3% (perampanel) and 100% (placebo) of patients showed no changes; 25.0% of patients showed improvements with perampanel whereas the worsening rate was 16.7%. For adolescent patients, all showed no changes, irrespective of treatment (Figure 1C).

Conclusions: At Week 18, based on the physician’s assessment, the majority of patients showed no changes in symptoms, regardless of treatment; the proportion of patients showing an improvement in symptoms was numerically greater for adjunctive perampanel vs placebo, however, similar trends were observed with worsening. Small variations were seen across age groups; however, interpretation of these data is limited due to small sample size.  

Funding: Eisai Co., Ltd., Eisai Inc., and Eisai Ltd.