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• Posted October 10, 2023

Experimental Drug Could Rein in Epilepsy Seizures

For people with tough-to-treat epilepsy, seizures can be both frightening and dangerous, but a new experimental pill may bring significant relief to over one-third of them.

Dubbed XEN1101, the new drug reduced the frequency of seizures by more than 50%, or even eliminated them, in some patients with focal epilepsy who did not respond to an average of six other drugs.

"I am predicting that with this drug there are going to be far fewer people with epilepsy who are going to be walking around and have no chance of getting their seizures controlled," said lead researcher Dr. Jacqueline French, a professor of neurology at NYU Langone Health in New York City.

Focal epilepsy is the most common type of epilepsy, French noted. "Two-thirds of people with epilepsy have focal epilepsy, which means that there's one area of focus in the brain where the seizures begin, whether it be in the temporal lobe or the frontal lobe, or wherever it is."

XEN1101 works differently than most other drugs used to treat epilepsy, she added.

"The drugs we use have different ways of decreasing the excitability of the brain. The most common drugs that we have are what we call sodium channel blockers. They prevent sodium from going into a cell," French said.

When sodium rushes into a cell, it fires the cell and sends that signal to the next cell, which sends it to the next cell and so on. "Most of the drugs we have blocked that," French explained

However, XEN1101 is a potassium channel opener, which means that it lets potassium out of the cell instead of keeping the sodium from going into the cell, which signals the cell not to fire, she said.

Like any drug, there are side effects. It can make people sleepy and it can make people unsteady. These side effects depend on the dose and are manageable, French said.

Another benefit of the drug is that it lasts in the body for a relatively long time, which means that patients don't have to take it as often as other anti-seizure medications, she noted. And unlike current medications that can take as long as 10 weeks to become fully effective, XEN1101 begins to act right away.

For the study, funded by drug maker Xenon Pharmaceuticals Inc., French and her colleagues randomly assigned 285 men and women with focal seizures to one of three doses of XEN1101, or a placebo. Participants had failed other drugs and had at least four seizures a month.

The investigators found that patients taking XEN1101 experienced a 33% to 53% drop in monthly seizures. Those taking the placebo had an average of only 18% fewer seizures during the eight weeks of the trial.

Given the option to continue taking the drug after the trial ended, most patients opted to continue treatment, and about 18% remained free from seizures after six months and about 11% after a year or more, French said.

More trials of the drug are in the works, and French hopes the drug will be approved and available for patients sometime in the next few years.

The report was published online Oct. 9 in JAMA Neurology.

"Patients should be hopeful for this drug and others that there is going to be a drug for them that controls their seizures," she said. "The fact that a seizure can occur anytime, anywhere is so disruptive to people's lives and it prevents them from working and from having relationships, and it's dangerous -- we need to stop those seizures -- yes, they should be hopeful."

One expert thinks this drug could be a much-needed addition to epilepsy care.

"It was a well-done trial by a group of international physicians, and it brings a new medication to market that has a novel mechanism action, which is quite different from other drugs that are currently available," said Dr. Sean Hwang, an assistant professor of neurology at Hofstra/Northwell School of Medicine in Hempstead, N.Y.

"I think it's a nice new medication for patients with seizures and epilepsy," Hwang said. "For some patients, this could really be a benefit."

More information

For more on epilepsy, head to the Epilepsy Foundation.

SOURCES: Jacqueline French, MD, professor, neurology, NYU Langone Health, New York City; Sean Hwang, MD, assistant professor, neurology, Hofstra/Northwell School of Medicine, Hempstead, N.Y.; JAMA Neurology, Oct. 9, 2023, online