Recent results from a clinical trial (Study 1; NCT02682927) of Fenfluramine (Fintepla;Zogenix, San Francisco, CA) showed that 2 different doses of Fenfluramine, when added to the participants’ existing treatment regimens for Dravet syndrome (DS), provided a significant reduction in convulsive seizure frequency compared to placebo.
Results showed that participants taking Fenfluramine at 0.7 mg/kg/day achieved a 62.3% greater reduction in mean monthly convulsive seizure frequency compared with those receiving placebo (95% CI -47.7 to -72.8, P<.0001). The same analysis for the group treated at 0.2 mg/kg/day versus placebo showed a 32.4% greater reduction in mean monthly convulsive seizure frequency compared with placebo (95% CI -6.2 to -51.3, P=0.0209).
More participants treated with Fenfluramine during the study achieved a clinically meaningful (≥ 50%) reduction in convulsive seizure frequency compared with those treated with placebo: 27 (68%) of 40 participants in the 0.7 mg/kg/day group (P<.0001) and 15 (38%) of 39 participants in the 0.2 mg/kg/day group (P=.0091), compared with 5 (12%) of 40 participants in the placebo group. Fenfluramine also provided significantly longer periods of seizure freedom to participants in the study: the median longest seizure free intervals were 25 days in the 0.7 mg/kg/day group (P=.0001) and 15 days in the 0.2 mg/kg/day group (P=.0352), compared to 9.5 days in the placebo group.
The most common adverse events, occurring in at least 10% of participants, and more frequently in those treated with Fenfluramine, were decreased appetite, diarrhea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed normal valve function and morphology in all participants during the trial and no signs of pulmonary arterial hypertension.
“The results from this study are tremendously encouraging in reducing the magnitude and duration of seizures in our patients with Dravet syndrome,” said Joseph Sullivan, MD, director of the Pediatric Epilepsy Center of Excellence at the UCSF Benioff Children’s Hospitals, colead author of the manuscript, and principal investigator. “If future outcomes are as positive, it could help clinicians set new standards of care for a treatment resistant disease like Dravet syndrome, in which frequent debilitating seizures and significant cognitive and functional impairments are the norm.”
Study 1 was an international, double blind, placebo-controlled phase 3 study of 119 participants with DS ages 2 to 18 years, who were treated at sites in the US, Canada, Europe, and Australia. Participants were randomized to 1 of 3 treatment groups: Fenfluramine at 0.7 mg/kg/day with a 26 mg maximum daily dose (n=40), Fenfluramine at 0.2 mg/kg/day (n=39), or placebo (n=40), which were added to the participant’s current antiepileptic drug regimen that excluded use of stiripentol. Following a 6-week baseline observation period, participants were titrated to their target dose over 2 weeks and remained at that dose for 12 weeks. The mean baseline convulsive seizure frequency across the study groups was approximately 40 seizures per month.
Peter McAllister, MD
Evanthia Bernitsas, MD
Mark B. Skeen, MD