Fintepla (formerly ZX008) is a treatment for Dravet syndrome, also known as severe myoclonic epilepsy of infancy. Developed by Zogenix, the oral medication is a low-dose solution of fenfluramine hydrochloride. Patients take the medication with other anti-epileptic treatments to reduce the frequency of seizures.
Fintepla was approved by the U.S. Food and Drug Administration (FDA) for use in patients 2 and older. Regulators in Belgium made low-dose fenfluramine available to epilepsy patients under the country’s compassionate use program after a long-term study of its potential.
What is Dravet syndrome?
Dravet syndrome is a rare form of epilepsy and usually caused by mutations in the SCN1A gene. This gene plays a key role in the healthy functioning of nerve cells in the brain. It contains the instructions necessary for the production of sodium channels in nerve cell membranes. These sodium channels are essential for the transmission of electrical signals between nerve cells.
In some patients with Dravet syndrome, the SCN1A gene is normal. Scientists suspect mutations in other related genes cause the disease in these cases.
Many of the medications that doctors use to treat other forms of epilepsy are ineffective in controlling seizures in Dravet syndrome. Some may even exacerbate them.
How does Fintepla work?
Doctors in Belgium have been adding low-dose fenfluramine to other therapies to treat Dravet syndrome patients for two decades as its use reduces the frequency of seizures. However, the mechanism by which the medication works is not known.
Initially, researchers thought that fenfluramine reduced seizures by affecting serotonin signaling in the brain. However, recent research suggests it may act on sigma receptors — a type of cell membrane receptor common in nerve cells.
Fintepla in clinical trials
Data supporting Fintepla’s approval came from two identical Phase 3 clinical studies, ZX008-1501 (NCT02682927) and ZX008-1502 (NCT02826863), and interim results from an ongoing open-label extension study (NCT02823145).
ZX008-1501 and another Phase 3 trial (NCT02926898) assessed the effects of different doses of Fintepla.
The open-label extension study is enrolling participants by invitation only and is assessing the long-term safety of Fintepla. Researchers evaluate patients every three months for up to 156 weeks (three years) of treatment. They record the frequency of seizures and any adverse events.
Researchers presented results from the open-label extension trial at the 48th Annual Meeting of the Child Neurology Society in October 2019. They showed that Fintepla reduced the median monthly frequency of convulsive seizures by 75% in children younger than age 6, compared with the start of the study. Similar results (a 64% reduction in seizure frequency) were found in the overall trial population, which included patients ages 2 to 18. The safety of the treatment was similar between older and younger patients. The most common adverse reactions were diarrhea, fever, inflammation of the nose and throat, and decreased appetite.
The ZX008-1502 trial is evaluating the effect of two doses of Fintepla in children and young adults. Researchers are looking at how the body absorbs and processes Fintepla, its safety, and its ability to reduce seizure frequency. Participants are receiving one of two doses of Fintepla or a placebo for 14 weeks. The trial continues to recruit participants in Japan, and researchers expect to complete it in July 2020.
Finally, a Phase 1/2 clinical trial (NCT03467113) is evaluating the safety of Fintepla in combination with a cannabis-based therapy, as a treatment for patients with Dravet syndrome and Lennox-Gastaut syndrome.
Fintepla labeling will include a warning that the medication is associated with valvular heart disease and pulmonary arterial hypertension. These potential complications require patients to undergo cardiac monitoring by echocardiogram before treatment, every six months during treatment, and one more time three to six months after treatment for the possibility of cardiac abnormalities.
Because of Fintepla’s potential complications, the FDA classified the medication as a Schedule IV controlled substance, which establishes controls over its prescription and distribution. Healthcare providers prescribing Fintepla and pharmacies distributing it must be specially certified. Patients receiving the medication must enroll in a risk evaluation and mitigation strategy program. Under the terms of this strategy, both prescribers and patients must adhere to the mandated cardiac monitoring in order to receive Fintepla.
Last updated: June 29, 2020
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