Results of a second phase 3 trial (Study 1504) and an ongoing open-label extension study (Study 1503) of fenfluramine for treatment of patients with Dravet syndrome showed that patients who took low-dose fenfluramine (Fintepla, Zogenix, Emeryville, CA) had reduced monthly convulsive seizure frequency.
Patients in Study 1504 were taking a background antiepileptic drug medication regimen that included stiripentol and were randomly assigned to receive placebo or fenfluramine (0.5 mg/kg/day). After a 6-week baseline observation period, patients were titrated to their target dose over 3 weeks, then remained at that fixed dose for 12 weeks. Results showed statistically significant efficacy of fenfluramine when added to a stiripentol regimen in children and young adults with Dravet syndrome.
Children and young adults treated with fenfluramine achieved a 54.0% greater reduction in mean monthly convulsive seizures compared with those treated with placebo. The median reduction in monthly convulsive seizure frequency was 63.1% for patients in the fenfluramine group compared to 1.1% in patients treated with placebo.
Interim analysis of the data from the open-label extension study (Study 1503) showed reductions in monthly seizure frequency as early as 1 month that continued over the entire treatment period. Decreased appetite was reported as a common adverse event (16%), with weight loss occurring in 13.4% of children. One patient died from SUDEP. Cardiac toxicity was not recorded as a common adverse event.
There was no evidence of valvular heart disease or pulmonary hypertension in any patient at any time during the trials. “Long-term safety results are a critical aspect of the profile for any investigational medicine,” said study author Dr. Wyman Lai, co-medical director, CHOC Children's Heart Institute. “I believe these results provide strong support that the positive benefit-risk profile of fenfluramine that was observed in both pivotal phase 3 trials extends to its longer-term use in the ongoing open-label extension trial.”
“This is an important study for adults with Dravet. Many of these patients have been institutionalized and may be receiving medications that are contraindicated,” commented Joseph Sullivan, University of California, San Francisco Benioff Children’s Hospital and clinical trial investigator. “If we could start a more appropriate treatment regimen that is more effective in reducing seizures, these patients could engage in more of their activities of daily living. That’s why early diagnosis is so important.”Next Story