Abstracts

Rationale:
FINTEPLA (fenfluramine, FFA) markedly reduced convulsive seizure frequency in 2 phase 3 clinical studies of children with Dravet syndrome (DS). Weight decrease is a known effect of FFA. Appetite disturbance is also common in DS. Decreased appetite was observed in FFA clinical trials, but most patients who initially lost weight resumed weight gain on treatment. In a recent study of 68 patients with DS, Eschbach (Seizure 2017;52:117-122) reported decreases in height and weight Z-scores of ~ 0.1 standard deviation (SD) for every 1-year increase in age. Z-score expresses weight- and height-for-age as the number of SD (Z-score) below or above the American CDC reference growth curve mean or median values. Here, we evaluate the impact of FFA on weight gain and growth in a long-term open-label extension study (OLE; Study 1503: NCT02823145).
Method:
Patients with DS (2-18 y/o) who completed 1 of 2 phase 3 placebo-controlled clinical studies and were eligible enrolled in the OLE. All patients received a 0.2-mg/kg/day starting dose and were titrated to effect (0.2-0.7 mg/kg/day FFA). Z-score analyses assessed potential impact of FFA on growth at OLE baseline, Month 12, and Month 24. Z-scores were determined by the Boston Children’s Hospital algorithm using height, weight, age, gender, body surface area, and body mass index. A mixed-effect model for repeated measures (MMRM) estimated changes in height and weight over time.
Results:
At time of analysis (Oct 14, 2019), 279 patients were treated with FFA for ≥ 12 months; 128 were treated for ≥ 24 months. Relative to the reference population, FFA treatment for ≥ 12 or ≥ 24 months did not result in a substantial impact on either height or weight over time as assessed by Z-score analyses in patients with available data (Table 1). Height and weight Z-scores were analyzed by FFA dose group (0.2 to < 0.3 mg/kg/day, 0.3 to < 0.5 mg/kg/day, and 0.5 to 0.7 mg/kg/day, averaged over time). No substantial dose-dependent changes from baseline were observed at Month 12 or 24 (Table 2). In MMRM, patients with ≥ 12 months (n=262) of FFA had an estimated change in Z-score per year of -0.056 for height and -0.166 for weight. In patients with all 3 time points (baseline, 12 months, and 24 months; n=110), estimated changes in Z-score per year were -0.025 for height and -0.188 for weight.