ZX008 is a treatment for a type of epilepsy called Dravet syndrome, which is also known as severe myoclonic epilepsy of infancy, or SMEI.

The oral medication is a low-dose solution of fenfluramine hydrochloride. Patients take it with other epileptic treatments to reduce the frequency of seizures.

ZX008 was developed by Zogenix, which specializes in treatments for central nervous system disorders and rare diseases.

How ZX008 works

Dravet syndrome is usually caused by a mutation of the SCN1A gene, which plays a key role in the healthy functioning of brain cells. The gene contains instructions for the production of the sodium channels in brain cell membranes. These sodium channels are essential to the transmission of electrical signals in the brain.

In some Dravet patients, the SCN1A gene is normal. Scientists suspect these cases are caused by mutations in related genes.

Many of the medications that doctors use to treat other forms of epilepsy fail to control  Dravet patients’ seizures.

Low-dose fenfluramine has been added to other therapies to treat Dravet patients in Belgium for two decades. Its use reduces the frequency of seizures.

Scientists don’t know exactly how fenfluramine works. Initially they thought it reduced seizures by affecting the brain’s serotonin neurotransmitter system. But recent research suggests it may work on sigma receptors — a type of cell membrane receptor common in brain cells.

ZX008 in clinical trials

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. Researchers have only recently begun conducting clinical trials of its safety and effectiveness.

These include five Phase 3 trials. Two (NCT02926898 and NCT02682927) are assessing  different doses of ZX008. They are ongoing but no longer recruiting participants. Both are expected to be completed in June of 2018.

Another Phase 3 trial (NCT02823145) is assessing ZX008’s long-term safety. It is enrolling participants by invitation only. Those who take part must have completed NCT02682927 or NCT02826863. They are being treated with ZX008 for up to 54 weeks, with researchers recording the frequency of their seizures and adverse events.

The fourth Phase 3 trial (NCT03299842) is evaluating the usefulness of an invention known as the Embrace seizure detection watch. The trial is an NCT02823145 sub-study. Participants are wearing the watch and using the Embrace Alert application connected with it for 12 weeks. The number of seizures that the watch detects will be compared with the number that patients record in a diary.

The fifth Phase 3 trial (NCT02826863) is evaluating the effect of two doses of ZX008 in children and young adults. Researchers are looking at how the body absorbs and processes ZX008, its safety, and its ability to reduce seizure frequency. Participants are receiving one of the two ZX008 doses or a placebo for 14 weeks. Researchers are continuing to recruit participants in Australia, Europe, and the U.K.

A Phase 1/2 trial (NCT03467113) is evaluating ZX008’s safety, in combination with a cannabis-based therapy, as a treatment for Dravet syndrome patients and Lennox Gastaut syndrome patients. It is enrolling participants by invitation only.

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