FDA Approves Drug for Seizures Associated with Dravet Syndrome

The US Food and Drug Administration (FDA) has approved Fintepla (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients aged two years and older. Two separate Phase III placebo-controlled clinical trials showed that the drug was able to significantly reduce the frequency of convulsive seizures in patients whose seizures could not be controlled by other medications.

Dravet syndrome is a rare, genetic, childhood-onset and life-threatening form of epilepsy that is characterized by severe, continued seizures often triggered by hot temperatures or fever. The seizures are difficult to treat with conventional anticonvulsant medications, warranting the need for better therapies.

The debilitating condition often appears in the first year of life, with seizures worsening with age. Dravet Syndrome is characterized by cognitive impairment, behavioral disorders and motor deficits.

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“Dravet syndrome is a debilitating disease that takes a tremendous toll on both patients and their families,” said Billy Dunn, Director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “Fintepla 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.”

The FDA approval was granted based on data from the two randomized, double-blinded, placebo-controlled Phase III clinical trials, which were published in The Lancet and JAMA Neurology, as well as safety data from an open-label extension trial in which patients received Fintepla for up to three years.

The trials evaluated the effectiveness of Fintepla in the treatment of Dravet syndrome-associated seizures and involved 202 participants between the ages of two and 18. The studies assessed the change in the frequency of convulsive seizures from baseline. Results of both trials showed that patients whose seizures could not be adequately controlled with standard antiepileptic drugs, experienced significantly greater reductions in the frequency of convulsive seizures when given Fintepla than those who received placebo. The changes were seen over a span of three to four weeks and remained consistent over the total 14- to 15-week treatment periods.

Fintepla is an oral, low-dose fenfluramine solution originally developed as an appetite suppressant. It functions to inhibit the reuptake of the neurotransmitter serotonin. New research suggests that Fintepla may also act on sigma receptors which are a type of cell membrane receptor commonly found on nerve cells.

The FDA granted the Fintepla application as Priority Review and gave approval for it to Zogenix Inc., a global pharmaceutical company developing rare disease therapies. It also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

In a press statement from Zogenix, Stephen J. Farr, President and Chief Executive Officer of the company said, “The approval of Fintepla by the FDA is a significant milestone we are proud to celebrate with the patients and families living with Dravet syndrome.” He explained that, “We began this global development program nearly six years ago after researchers in Belgium recognized the potential of fenfluramine, a drug with distinct pharmacology from all other anticonvulsant agents, to treat intractable seizures in Dravet syndrome. Our heartfelt gratitude goes to the patients, families, and everyone who supported the rigorous development program that led to Fintepla’s approval.”

Fintepla has some adverse side effects, with the most serious being the development of valvular heart disease and pulmonary arterial hypertension. Because of this, patients using Fintepla must be monitored for potential cardiac abnormalities through echocardiogram before treatment, every six months during treatment and once more three to six months after treatment.

Given this, the FDA has classified Fintepla as a Schedule 4 controlled substance, which will be made available through a restricted program called the Fintepla Risk Evaluation and Mitigation Strategy (REMS). Under the program, both prescribers and patients must be in compliance with the mandated cardiac monitoring in order to receive the drug, and providers and pharmacies must have special certification for its distribution.

Mary Anne Meskis, executive director of the Dravet Syndrome Foundation, said in the press release, “Having a new FDA-approved treatment option is so important because it improves our ability to optimize each patient’s treatment.”

Zogenix has also established Zogenix Central, a support service to assist patients who receive the treatment, as well as their caregivers and medical teams.

“Because families living with Dravet syndrome never know when the next seizure is going to occur, whether they will end up in the [emergency room], or what the consequences might be following the seizure, having a strong support program like Zogenix Central to reduce the strain on families is very welcome. This will allow family members to remain focused on providing the best care of their loved one with Dravet,” said Meskis.

The commercial launch of Fintepla is scheduled for July 2020.