Fenfluramine Indication Expansion to Include Lennox-Gastaut Syndrome Submitted to FDA 

A supplemental new drug application (sNDA) has been submitted to the Food and Drug Administration (FDA) for fenfluramine (Fintepla; Zogenix, Emeryville, CA) to treat seizures associated with Lennox-Gastaut Syndrome (LGS). 

In a randomized controlled phase 3 clinical trial (NCT03355209) in 263 participants (age 2 to 35 years), 0.7/mg/kg/day of fenfluramine was superior to placebo in reducing the frequency of drop seizures (P=.001). The proportion of participants who had a 50% or more reduction in seizures was also higher with fenfluramine vs placebo.

In an open-label extension of this trial, after 3 months of treatment, participants with LGS had a 39.4% (P<.0001) median reduction of drop seizures of 39.4% from a median baseline of 75 (range 4-2,943). For those who have been treated for 10 to 12 months (n=170), median drop seizure reduction has been 51.8% and more than half have had a 50% or more reduction in seizures with 25.3% achieving a 75% or more reduction. 

“As LGS is a severe, rare form of epilepsy that is not well-controlled by currently available antiseizure medications, we believe that Fintepla, if approved, would become an important new treatment option that addresses a significant unmet need for this patient population,” said Gail Farfel, PhD, executive vice president and chief development officer, Zogenix.

Fenfluramine has been generally well-tolerated. There has been no observed valvular heart disease or pulmonary hypertension and the most common adverse events have been decreased appetite (n=40, 16.2%), fatigue (n=33, 13.4%), nasopharyngitis (n=31, 12.6%) and seizure (n=27, 10.9%). An individual death occurred which was considered unrelated to study drug.