The US Food and Drug Administration (FDA) has approved fenfluramine (Fintepla, Zogenix) oral solution, a Schedule IV controlled substance, for the treatment of seizures associated with Dravet syndrome in children age 2 years and older.
Dravet syndrome is a rare childhood-onset epilepsy characterized by frequent, drug-resistant convulsive seizures that may contribute to intellectual disability and impairments in motor control, behaviour, and cognition, as well as an increased risk of sudden unexpected death in epilepsy (SUDEP).
Dravet syndrome takes a “tremendous toll on both patients and their families. Fintepla offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome,” Billy Dunn, MD, director, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a news release.
The FDA approved fenfluramine for Dravet syndrome based on the results of two randomized, double-blind, placebo-controlled phase 3 trials involving children aged 2 to 18 years with Dravet syndrome.
In both studies, children treated with fenfluramine experienced significantly greater reductions in the frequency of convulsive seizures than their peers who received placebo. These reductions occurred within 3 to 4 weeks, and remained generally consistent over the 14- to 15-week treatment periods, the FDA said.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even while taking one or more of the currently available antiseizure medications,” Joseph Sullivan, MD, who worked on the fenfluramine for Dravet syndrome studies, said in a company news release.
Given the “profound reductions” in convulsive seizure frequency seen in the clinical trials, combined with the “ongoing, robust safety monitoring,” fenfluramine offers “an extremely important treatment option for Dravet syndrome patients,” said Sullivan, director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco (UCSF) Benioff Children’s Hospital.
Fenfluramine is an anorectic agent that was used to treat obesity until it was removed from the market in 1997 over reports of increased risk of valvular heart disease when prescribed in higher doses and most often when prescribed with phentermine. The combination of the two drugs was known as fen-phen.
In the clinical trials of Dravet syndrome, the most common adverse reactions were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; increased blood pressure; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; and status epilepticus.
The Fintepla label has a boxed warning stating that the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Due to these risks, patients must undergo echocardiography before treatment, every 6 months during treatment, and once 3 to 6 months after treatment is stopped.
If signs of VHD, PAH, or other cardiac abnormalities are present, clinicians should weigh the benefits and risks of continuing treatment with Fintepla, the FDA said.
Fintepla is available only through a risk evaluation and mitigation strategy (REMS) program, which requires physicians who prescribe the drug and pharmacies that dispense it to be certified in the Fintepla REMS and that patients be enrolled in the program.
As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring to receive the drug.
Fintepla will be available to certified prescribers in the United States in July. Zogenix is launching Zogenix Central, a comprehensive support service that will provide ongoing product assistance to patients, caregivers, and their medical teams. Further information is available online.