Fenfluramine hydrochloride for the treatment of Dravet syndrome

ABSTRACT

Introduction: Fenfluramine (3‐trifluoromethyl‐N‐ethylamphetamine), a former anorectic agent, has been successfully repurposed for Dravet syndrome (DS).

Area covered: A systematic review of data on fenfluramine in the treatment of patients with DS has been conducted, with 11 published papers on the use of fenfluramine for DS (six clinical trials, of which two were randomized controlled trials (RCTs), and five preclinical studies). Following clinical observations suggesting the efficacy of fenfluramine, the effect on convulsive seizures has been confirmed by two RCTs. The first RCT demonstrated the efficacy of the two tested doses of 0.2 mg/kg/day and 0.7 mg/kg/day, while the second RCT showed the efficacy of 0.4 mg/kg/day fenfluramine in patients with DS treated with stiripentol.

Expert opinion: Preclinical studies provide insights into the mechanisms of action of fenfluramine. There are still no large real-life studies. Fenfluramine is under investigation for the treatment of other epilepsy syndromes.

KEYWORDS:

• Antiseizure medication
• Dravet syndrome
• epilepsy
• fenfluramine
• randomized trials

Article highlights

• Fenfluramine, a former anorectic agent, has been successfully repurposed for Dravet syndrome

• Few open studies have suggested that fenfluramine has anticonvulsant properties

• Two randomized controlled trials have established the efficacy of fenfluramine in Dravet syndrome

• Currently, there is no negative sign on the occurrence of cardiac side effects.

This box summarizes key points contained in the article.

Declaration of interest

B Dozières-Puyravel has received honoraria for lectures from Eisai and UCB Pharma; has been coinvestigator for clinical trials for Advicenne Pharma, Eisai, UCB Pharma and Zogenyx. S Auvin has served as consultant or received honoraria for lectures from Advicenne Pharma, Biocodex, Eisai, GW Pharma, Novartis, Nutricia, Shire, UCB Pharma, Ultragenyx, Zogenyx and has been investigator for clinical trials for Advicenne Pharma, Eisai, UCB Pharma and Zogenyx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.