Abstracts

Patients with Dravet syndrome (DS) often require polypharmacy with multiple concomitant antiepileptic drugs (AEDs) for seizure management. The objective of this analysis was to evaluate the efficacy of add-on fenfluramine (FFA) when used in different combinations of commonly used concomitant AEDs in DS: stiripentol, clobazam, and/or the combination of clobazam/valproate.

Patients with Dravet syndrome (ages 2-18 years, inclusive) who were enrolled in 2 double-blind, parallel-group, placebo-controlled phase 3 studies (Study 1, NCT02682927, NCT02826863; Study 1504, NCT02926898) were included in this analysis. Depending on the study, patients received FFA doses ranging from 0.2 to 0.7 mg/kg/day (maximum daily doses: 26 mg/day without stiripentol and 17 mg/day with stiripentol). Percent difference in convulsive seizure frequency per 28 days (monthly convulsive seizure frequency, MCSF) was calculated from baseline relative to the combined titration and maintenance periods. Differences among subgroups were statistically evaluated using an analysis of covariance model (ANCOVA; α=0.05).

A total of 206 patients with DS were enrolled in the double-blind studies (placebo: n=84; 0.2 mg/kg/day FFA: n=39; 0.4 mg/kg/day FFA: n=43; 0.7 mg/kg/day FFA: n=40), with a median age of 8.5 years (range, 2-19 years) and a mean (+-SD) body mass index of 18.4+-4.3; 55.3% were male. FFA provided clinically meaningful relief in patients with or without stiripentol (change in MCSF from prerandomization baseline without stiripentol: ‑62.3%, P<0.001; with stiripentol: ‑54.0%, P<0.001); with or without clobazam (without clobazam: ‑57.2%, P<0.001; with clobazam: ‑52.4%, P<0.001), and with or without the combination of clobazam/valproate (without combination: ‑49.8%,