Xenon Pharmaceuticals announced positive results on Mar. 9 from a Phase 3 trial of its lead candidate for focal onset seizures, moving the company closer to its first regulatory approval after more than 25 years in operation.
The announcement is significant as it marks a potential breakthrough for patients with uncontrolled seizures and could introduce a new class of treatment for epilepsy. Xenon's drug, azetukalner, is a novel Kv7 potassium channel opener and would be the first of its kind if approved.
According to Xenon CEO Ian Mortimer, "The Phase 3 data exceeded expectations and, to our knowledge, show the highest placebo-adjusted efficacy ever observed in a pivotal epilepsy study." Stifel analysts said in a note that the data from the X-TOLE2 trial "represent [a] best-case scenario--beating the high bar set in ph2b and demonstrating a best-in-class profile." Following these results, Xenon's stock price rose nearly 45% to over $60 in pre-market trading.
In the X-TOLE2 study, azetukalner met its primary endpoint by reducing the frequency of focal onset seizures by 53.2% at the higher dose compared to only a 10.4% reduction with placebo. The lower dose group saw a reduction of 34.5%. These results improved upon those seen in an earlier Phase 2b study. The safety profile remained consistent with previous trials. In an ongoing open-label extension study linked to X-TOLE, Xenon reported that 38% of patients were seizure-free after one year or longer.
Chief Medical Officer Chris Kenney said azetukalner works by inhibiting neuronal firing through blocking potassium ion channels: "which play a major role in calming down neurons after they fire." Kenney also noted that while there are already about twenty epilepsy drugs available—mainly SV2A binders and sodium channel blockers—azetukalner offers a differentiated mechanism: "would be sort of the third leg of the stool." Beyond epilepsy, azetukalner is being studied for major depressive disorder and bipolar depression.
Mortimer reflected on Xenon's journey since its founding as a genetics company in November 1996: "Over the past 15–20 years, the company has built up its drug discovery and clinical development capabilities in drugging ion channels in the nervous system." He added that much focus has been on Kv7 channels recently. Regarding azetukalner's future prospects, Mortimer said: "the magnitude of effect in X-TOLE2, favorable safety profile, differentiated Kv7 mechanism of action and ease-of-use attributes give the company great confidence in azetukalner’s potential to become a preferred medication for patients living with uncontrolled seizures."
With plans to submit an application for FDA approval later this year, observers will be watching closely as Xenon seeks to bring this new therapy to market.
