Fintepla (fenfluramine) is an add-on 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, and taken with other anti-epileptic treatments to reduce the frequency of seizures.
Both the U.S. Food and Drug Administration (FDA) and the European Commission approved Fintepla to treat patients 2 and older in 2020.
What is Dravet syndrome?
Dravet syndrome is a rare form of epilepsy 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 Dravet patients, 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 for many Dravet patients. A few may even exacerbate seizures.
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. The mechanism by which the medication works, however, is not clear.
Researchers initially thought that fenfluramine reduced seizures by affecting serotonin signaling in the brain. More recent research suggests it acts 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 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, which concluded in December 2020, enrolled 158 patients, ages2 to 18, from the 1501 and 1502 studies to assess safety of Fintepla’s long-term use, given daily as an oral solution of up to 20 or 30 mg. Patients were evaluated every three months for up to 156 weeks (three years), with the frequency of seizures and possible treatment side effects among key measures recorded.
Researchers presented results from the 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 (baseline). Similar results (a 64% reduction in seizure frequency) were seen in the overall trial population. 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 low appetite.
The ZX008-1502 trial (also called Study 3) evaluated the effect of two doses of Fintepla in 143 patients, ages 2 to 18, whose seizures were not controlled by existing anti-epileptic medicines. Researchers looked at how the body absorbed and processed Fintepla, its safety, and its ability to reduce seizure frequency.
Participants received one of two doses of Fintepla (0.2 mg/kg per day or 0.7 mg/kg per day) or a placebo — all given as an add-on to each patient’s current anti-epileptic medications — for 12 weeks. Treatment started after a six-week observation period when baseline measures were taken, and found these children had an average of 63 seizures each month.
Results showed that patients on the higher dose of Fintepla had an average 64.8% reduction in the number of monthly seizures compared with those on a placebo. Those on the lower dose saw a 49.9% reduction in monthly seizures. Although Fintepla has been associated with cardiac problems, none were reported in treated patients during the study, which monitored their heart health.
A Phase 1/2 clinical trial (NCT03467113) was evaluating the safety of Fintepla given in combination with a cannabis-based therapy in people with Dravet syndrome and Lennox-Gastaut syndrome. This trial was expected to end in August 2020; results are not yet available.
Fintepla labeling includes a boxed warning that the medication is associated with valvular heart disease and pulmonary arterial hypertension. These potential complications require patients to undergo cardiac monitoring via an echocardiogram before treatment, every six months during treatment, and once more three to six months after stopping treatment for possible cardiac abnormalities.
Because of Fintepla’s potential complications, the FDA classified the medication as a schedule 4 controlled substance, which restricts its distribution, and places it under a risk evaluation and mitigation strategy. This is due to the need for cardiac monitoring of treated patients.
The most common side effects reported in clinical studies included decreased appetite; drowsiness, sedation and lethargy; diarrhea; constipation; abnormal echocardiogram; fever; fatigue or lack of energy; ataxia (lack of coordination), balance disorder, gait disturbance (trouble with walking); and increased blood pressure.
Last updated: Jan. 15, 2021
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