FINTEPLA (fenfluramine) was recently approved by the FDA for the treatment of seizures in Dravet syndrome. The FDA required Zogenix, Inc to include a black box warning on the label because fenfluramine belongs to a class of drugs that affect a specific serotonin receptor (5-HT2B), and these types of drugs have previously been associated with valvular heart disease and pulmonary hypertension. Additionally, the FDA required a Risk Evaluation and Mitigation Strategy (REMS) Program that requires regular monitoring of patient heart health before, during, and after taking FINTEPLA. These requirements have generated interest in the effects of FINTEPLA (fenfluramine) on heart health in patients with Dravet syndrome. Notably, the previous associations of fenfluramine and serious heart issues were from higher doses (60-120 mg/day) used as a weight loss drug for adult obesity for longer than three to six months. Results from the initial 15-week trial of low-dose fenfluramine (max 26 mg/day) in patients with Dravet syndrome did not reveal any serious heart issues, but longer-term studies were still needed.
In this publication, Lai et al detail the cardiovascular results of 232 patients with Dravet syndrome (aged 2-18 years) taking fenfluramine in an open-label extension study by Zogenix, Inc. Patients examined in this clinical study took fenfluramine for 58 to 634 days (median duration 256 days) and received echocardiograms 4-6 weeks after beginning fenfluramine and again every three months for the duration of treatment. None of the patients enrolled in this long-term extension study exhibited any serious cardiac issues, with no cases of valvular heart disease or pulmonary hypertension. There were some findings (23%) of trace mitral valve regurgitation, and a single finding of trace aortic valve regurgitation; however, these results were often found only transiently within individual patients and resolved at subsequent examinations. Trace valve regurgitation is generally considered physiologic when other structural heart valve abnormalities are absent. The authors conclude that fenfluramine, the active ingredient in FINTEPLA, appears to be a low risk factor for serious cardiac issues when used at a low-dose in patients with Dravet syndrome.