The approval is based on data from 2 randomized, double-blinded, placebo-controlled phase 3 trials.
Fenfluramine labeling includes a boxed warning due to associations of the drug with valvular heart disease and pulmonary arterial hypertension. Because of this, the oral solution will be launched through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy program. The program will be available through Zogenix’s specialty pharmacy partner.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even when taking one or more of the currently available anti-seizure medications,” Joseph Sullivan, MD, principal investigator for fenfluramine in Dravet syndrome, said in a statement.
The rare childhood-onset epilepsy is characterized by frequent and severe treatment-resistant seizures. Dravet syndrome is associated with hospitalizations and medical emergencies, significant developmental and motor impairments, and an increased risk of sudden unexpected death.
The approval was based on data from 2 randomized, double-blinded, placebo-controlled phase 3 trials, along with safety data from an open-label extension trial where many patients received fenfluramine for up to 3 years. The findings are published in The Lancet and JAMA Neurology.
Sullivan and the team of investigators noted when fenfluramine was added to existing treatment regimens, it significantly reduced the monthly convulsive seizure frequency compared to placebo in patients whose seizures were not adequately controlled on 1 or more antiepileptic drugs. A majority of study patients responded to treatment within 3-4 weeks and effects remained consistent over the treatment period.
“Given the profound reductions in convulsive seizure frequency seen in the FINTEPLA clinical trials, combined with the ongoing, robust safety monitoring that will be part of its use, I feel FINTEPLA will offer an extremely important treatment option for Dravet syndrome patients," Sullivan said.
Common adverse events with an incidence of at least 10% or greater than placebo included decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, and abnormal echocardiogram. Additional adverse reactions included fatigue, vomiting, decreased weight, increased blood pressure, upper respiratory tract infection, and drooling, among others.
Certified prescribers will have access to fenfluramine in the US in July. Further, Zogenix is launching Zogenix Central to provide ongoing product assistance to patients, caregivers, and their medical teams.
The program will reduce the strain on families who never know when the next seizure is going to occur or whether they will end up in the emergency department, Mary Anne Meskis, executive director of the Dravet Syndrome Foundation, said.
"Having a new FDA-approved treatment option is so important because it improves our ability to optimize each patient's treatment," Meskis said.