Fenfluramine helps minimize day-to-day seizure burden in Dravet syndrome
Treatment with fenfluramine in patients with Dravet syndrome (DS) appears to produce a marked reduction in day-to-day seizure burden and provide prolonged periods of convulsive seizure-free days, as shown in a study.
Researchers conducted a post hoc time-to-event (TTE) analysis using data from two phase III placebo-controlled trials of adjunctive fenfluramine for DS (study 1, n=119; study 2, n=87) to evaluate the time required postrandomization for each patient to experience the same number of seizures experienced during baseline (ie, time-to-nth seizure). The fenfluramine doses evaluated were 0.7 mg/kg/day and 0.2 mg/kg/day in study 1, and 0.4 mg/kg/day with stiripentol in study 2.
Compared with placebo, fenfluramine was associated with a greater proportion of patients who never reached baseline seizure frequency (study 1: 60 percent with 0.7 mg/kg/day, 31 percent with 0.2 mg/kg/day, and 13 percent with placebo; study 2: 58 percent with 0.4 mg/kg/day and 2 percent with placebo).
Patients on fenfluramine vs placebo also had a longer median time-to-nth seizure (study 1: 13 weeks with 0.7 mg/kg/day, 10 weeks with 0.2 mg/kg/day, and 7 weeks with placebo; study 2: 13 weeks with 0.4 mg/kg/day and 5 weeks with placebo; p<0.001).
Furthermore, the longest duration of convulsive seizure-free days was observed in the active treatment groups (study 1: 25.0 days with 0.7 mg/kg/day, 15.0 days with 0.2 mg/kg/day, and 9.5 days with placebo [p=0.0001; p=0.0352]; study 2: 22 days with 0.4 mg/kg/day and 13.0 days with placebo [p=0.004]).
The most common adverse events were decreased appetite, pyrexia, upper respiratory tract infection, diarrhoea, and fatigue.
The encouraging results with fenfluramine may have important implications. Specifically, it can help reduce the physical and emotional disease toll while improving health-related quality of life for patients and caregivers.