Xenon’s Add-On Epilepsy Treatment Shows Promising Phase IIb Efficacy, Safety

MRI Scans_iStock, Nur Ceren Demir

Pictured: MRI scans of a brain/iStock, Nur Ceren Demir

Results from the Phase IIb X-TOLE study showed that Xenon Pharmaceuticals’ investigational potassium channel opener XEN1101 could safely reduce seizure burden in adults with focal epilepsy, the company announced Monday.

The data, published Monday in the journal JAMA Neurology, came from a randomized, double-blinded, parallel-group and placebo-controlled mid-stage study of 325 patients suffering from focal-onset seizures—the most common type of epileptic seizures. XEN1101 treatment led to a dose-dependent drop in seizure burden and the effect was significantly better than placebo at all dose levels.

At 25 mg, seizure frequency dropped by a median of 52.8% after eight weeks of treatment, while the 20-mg dose reduced seizures by 46.4% versus baseline. Even at the lowest dose level of 10 mg, XEN1101 led to a significant 33.2% decrease in seizure frequency from baseline compared with placebo, which was only associated with an 18.2% reduction.

In terms of safety, X-TOLE found Xenon’s candidate to be generally well-tolerated. The observed treatment-emergent adverse events were broadly in line with other drugs in the same class. None of the toxicities led to death.

“XEN1101 continues to demonstrate its efficacy through sustained seizure reduction and a compelling product profile with once-daily dosing with food and no titration required,” Xenon CEO Ian Mortimer said in a statement.

With these latest data, Xenon will “continue to advance” the candidate through its Phase III development in the X-TOLE2 and X-TOLE3 studies in focal-onset seizures as well as the X-ACKT trial in primary generalized tonic-clonic seizures, Mortimer said.

XEN1101 is a selective small molecule opener of the Kv7.2/Kv7.3 voltage-gated potassium channels, dysfunctions in which have been linked to seizures. By enhancing the opening of these channels, XEN1101 could help prevent seizures.

Also targeting Kv7.2/Kv7.3 voltage-gated potassium channels is pharma company Biohaven. Like XEN-1101, its candidate BHV-7000 is a selective activator of the channel, which in turn facilitates neuronal signaling and prevents seizures. Last month, Biohaven posted positive electroencephalogram biomarker data for the candidate at projected therapeutic concentrations, which could point to its potential as an antiseizure treatment.

With these promising biomarker data, Biohaven is pushing through with Phase III development for BHV-7000 in focal epilepsy, which is set to begin before the year ends.

Biohaven is an established leader in the neurology and migraine space. In May 2022, its predecessor company Biohaven Pharmaceuticals was acquired by Pfizer for more than $11 billion. Following the buyout, Biohaven launched anew on October 2022 with its renewed focus on the Kv7 ion channel.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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