Fenfluramine May Usher in Higher Standards for Treatment of Dravet Syndrome

In an editorial in Epilepsy and Behavior, Helen Cross, MD and Joseph Sullivan, MD suggest fenfluramine (Fintepla; Zogenix, Emeryville, CA) clinical trial results can raise the bar for efficacy of antiseizure medications (ASMs) for Dravet syndrome. They note that fenfluramine achieved responder rates for seizure reduction at the 75% or more level at a time when 50% and higher reductions are still considered effective in clinical trials. The authors suggest that future potential treatments for Dravet syndrome “should be evaluated against the demonstrated efficacy of fenfluramine,” which would create a significantly higher standard of efficacy for clinical trials. 

“Our primary goal in treating Dravet syndrome patients is to safely reduce the number and severity of seizures that contribute to poor long-term neurodevelopmental outcome and higher risk of death,” said Joseph Sullivan, MD, UCSF Benioff Children’s Hospitals. “With the availability of more approved treatment choices and the significant levels of seizure reduction seen with fenfluramine, we now have additional tools to achieve profound seizure reduction, better neurodevelopmental outcomes, and improved quality of life for a large percentage of our patients.”

Dr. Sullivan and Cross' assessment is based on a body of previously released data from the clinical trials supporting fenfluramine regulatory reviews, data from up to 3 years of an ongoing open-label study, and early-access programs. Across studies, fenfluramine provides safe, effective, and durable seizure reduction for a majority of those treated, including individuals who had continued high seizure burdens despite treatment with 1 or more other ASMs.

Across studies, fenfluramine has been generally well-tolerated, with no observed cases of pulmonary arterial hypertension or valvular heart disease. The most common adverse events were reported as decreased appetite, fatigue, diarrhea, and somnolence.