Fenfluramine halves seizure frequency in Dravet syndrome

Fenfluramine appears to reduce the incidence of seizure by half over about a year of treatment in children and adolescents with Dravet syndrome while having a tolerable safety profile, according to a study.

The open-label extension study included 232 patients who received fenfluramine at 0.2 mg/kg/d for a median of 256 days (range 46–634). At 4 weeks, dose was allowed to be titrated based on efficacy and tolerability to maximum of 0.7 mg/kg/d or maximum of 0.4 mg/kg/d in patients receiving concomitant stiripentol.

Over the entire follow-up, convulsive seizure frequency decreased from baseline by a median of 66.8 percent (range, –100 percent to –234.9 percent; p<0.001). The anticonvulsive effectiveness of the drug was comparable between patients aged <6 and ≥6 years (−75.7 percent vs −64.7 percent).

Notably, more than 40 percent of patients achieved a huge (>75 percent) reduction in convulsive seizure frequency.

Treatment was well tolerated, and none of the patients developed cardiac valvulopathy or pulmonary hypertension. Commonly reported adverse events were pyrexia (21.6 percent), nasopharyngitis (19.4 percent), and decreased appetite (15.9 percent).

The findings show that fenfluramine yields clinically meaningful and ongoing marked seizure reduction over a substantial period of time. This has important clinical implications, given the negative impact of frequent convulsive seizures on long‐term neurodevelopmental outcomes in the patients with Dravet syndrome.