Schedule IV controlled substance approved to reduce seizures in patients 2 years and older

WASHINGTON — The FDA approved fenfluramine (Fintepla) to treat seizures associated with Dravet syndrome, a rare and potentially fatal form of epilepsy, in patients 2 years and older.

Fenfluramine — an amphetamine derivative, which was previously used as an appetite suppressant before being pulled from the U.S. market due to safety concerns following reports of valvular heart disease (VHD) in patients using the drug — is a DEA Schedule IV controlled substance. Due to the risk of VHD and pulmonary arterial hypertension (PAH), fenfluramine carries a boxed warning and is only available through a restricted drug distribution program under a risk evaluation and mitigations strategy (REMS), the FDA announced.

“Dravet syndrome is a debilitating disease that takes a tremendous toll on both patients and their families,” said Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “[Fenfluramine] offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome. The FDA will continue to work with companies on drug development for Dravet syndrome and other types of epilepsy.”

This approval was based on results from a pair of clinical studies that assessed the efficacy of fenfluramine versus placebo in a cohort of 202 patients from ages 2-18 with Dravet syndrome.

“In both studies, subjects treated with [fenfluramine] had significantly greater reductions in the frequency of convulsive seizures during the trials than subjects who received placebo,” the agency explained. “These reductions were seen within 3-4 weeks, and remained generally consistent over the 14- to 15-week treatment periods.” Based on these results, the agency granted fenfluramine Priority Review and Orphan Drug designations.

Due to the risk of VHD and PAH associated with this drug, patients must receive cardiac monitoring using echocardiograms before treatment, evrry six months over the course of treatment, and a final time three to six months after discontinuation of treatment. “If the echocardiogram shows signs of VHD, PAH, or other cardiac abnormalities, health care professionals must consider the benefits and risks of continuing treatment with [fenfluramine] for the patient,” the FDA wrote.

“The [fenfluramine] REMS requires health care professionals who prescribe [fenfluramine] and pharmacies that dispense [fenfluramine] to be specially certified in the [fenfluramine] REMS and that patients be enrolled in the REMS,” the agency continued. “As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring with echocardiograms to receive [fenfluramine].”

The most commonly reported side effects of fenfluramine for this indication included decreased appetite; drowsiness, sedation, and lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue; ataxia, balance disorder, and gait disturbance; increased blood pressure; drooling and salivary hypersecretion; fever; upper resipratory tract infection; vomiting; weight loss; risk of falls; and status epilepticus.

Fenfluramine is manufactured by Zogenix, Inc.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 130

Topic ID: 82,130,730,130,34,192,725