Phase III study of Brabafen in Dravet Syndrome published in JAMA Neurology.- Zogenix

Using Brabafen (fenfluramine) from Zogenix in an antiseizure medication regimen that includes the anticonvulsant stiripentol significantly reduces seizures in Dravet syndrome (DS) according to results of a phase III, randomized, placebo-controlled trial published online in JAMA Neurology. The study also showed no cardiovascular side effects, which is important given the history of fenfluramine with respect to the risk of valvular heart disease and pulmonary arterial hypertension (PAH). The multicenter study included 87 patients (57% male, mean age 9.1 years). Participants had to be free of cardiovascular disease and have poorly controlled seizures on their current drug regimen.

At baseline, participants were experiencing high numbers of seizures. Oral fenfluramine (0.4 mg/kg/d; maximum 17 mg/d) provided a 54.0% greater reduction in mean monthly convulsive seizure frequency than placebo in patients with Dravet syndrome who were taking stiripentol-containing antiepileptic drug regimens; a significantly greater proportion of patients who were taking fenfluramine (vs placebo) experienced a clinically meaningful (at least 50%) or profound (at least 75%) reduction in monthly convulsive seizure frequency. The most common adverse events included decreased appetite, pyrexia, fatigue, and diarrhea; no patient developed valvular heart disease or pulmonary hypertension.

After the initial titration period, patients received fenfluramine or placebo for an additional 12 weeks and then continued treatment in an open-label extension study or discontinued treatment with a blinded, downward dose-tapering protocol. Three in the placebo group and seven in the fenfluramine group withdrew early.

See: Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome "Receiving Stiripentol-Inclusive RegimensA Randomized Clinical Trial" Rima Nabbout et al. JAMA Neurol. Published online December 2, 2019. doi:https://doi.org/10.1001/jamaneurol.2019.4113