A new drug application (NDA) has been submitted to the Food and Drug Administration (FDA) for low-dose fenfluramine (Fintepla, previously known as ZX008; Zogenix, Emeryville, CA) for the treatment of seizures associated with Dravet syndrome. The NDA is based on data from 2 phase 3 clinical trials and an open-label extension study. A simultaneous application to the European Marketing Agency (EMA) has also been filed.
In 1 of the phase 3 trials (Study 1504), children and young adults treated with low-dose fenfluramine had a 54% greater reduction in mean monthly convulsive seizures compared with those who were treated with placebo (P < .001). The median reduction in monthly convulsive seizure frequency was 63.1% for patients treated with fenfluramine compared to 1.1% in patients given placebo. There was also an increase in convulsive seizure-free intervals for patients treated (median interval = 22 days) with low-dose fenfluramine (0.5 mg/kg/day) compared to those treated with placebo (median interval = 13 days).
Data from the interim analysis of the open-label extension trial are also included in the NDA and show that patients treated with low-dose fenfluramine had reduced monthly seizure frequency as early as 1 month after starting treatment that lasted over the entire treatment period, which had a median of 256 days and a maximum of 21 months. Although decreased appetite and weight loss were common across all the studies, there were no signals of cardiac toxicity, valvular heart disease, or pulmonary hypertension.
“Our concurrent submissions to the FDA and EMA are the culmination of four years’ effort for Zogenix, our investigators, and the families who participated in the ZX008 clinical trial program,” said Stephen J. Farr, President and Chief Executive Officer of Zogenix. “We are honored to have partnered with such dedicated people to develop a potential new treatment for this rare and often catastrophic disease and look forward to working closely with the FDA and EMA during the review process.”