New treatments can arrive along a variety of pathways, and this review article describes an example of using a known drug in a new way – in this case, the trail by which fenfluramine became a drug candidate for Dravet Syndrome.
Fenfluramine was found to accelerate weight loss in the 1960’s, and was approved as an obesity therapy in 1973. Fenfluramine raises levels of the neurotransmitter called serotonin. It was known that several anti-convulsants also raise serotonin levels. Further, many anti-depressants raise serotonin levels, and patients taking these drugs, who also had seizure disorders, noticed that they improved their seizure issues. Based on all these connections, neurologists began investigating fenfluramine as an epilepsy treatment, including in children. However, in 1997, fenfluramine was withdrawn from the market due to cardiovascular problems. It was found that withdrawal in epilepsy patients led to resumption of seizures, and in 2002 the Belgian government re-allowed fenfluramine to be used, at low doses in children with intractable epilepsy (most of whom were later classified as having Dravet syndrome upon genetic testing). Over time, the Belgian studies established that fenfluramine was very promising as a Dravet therapy, and that the low doses avoided serious cardiovascular liabilities.
Currently, a low-dose fenfluramine formulation (“Fintepla”) has been showing encouraging results as an add-on therapy against Dravet syndrome in Phase III clinical studies in the U.S.