Xenon Pharmaceuticals’ anti-seizure candidate has smashed a pivotal trial out of the park, lowering seizure rates by more than 50% for some patients as it looks to position itself to become the standard of care in the field.
In the phase 3 X-Tole2 study, Xenon’s KV7 potassium channel opener azetukalner significantly reduced focal onset seizure frequency at the 12-week mark by 53.2% when given at 25 milligrams daily and by 34.5% at 15 milligrams daily. The placebo group’s seizure rate, meanwhile, dropped by about 10%. Xenon revealed the results March 9 along with plans to submit the pill for FDA approval in the third quarter of this year.
“Good things come to those who wait,” analysts from William Blair wrote in a March 9 note. The result “blows away” their expectations of an about 30% reduction in seizures, the analysts wrote, and, coupled with a solid tolerability profile, the pill’s ease of use and ability to be combined with other drugs, sets up azetukalner to become the epilepsy medicine of choice.
The most common side effect of treatment was dizziness, which affected one-fifth of patients given azetukalner. Adverse events became worse at higher doses, with 14.5% of patients given 25 mg daily discontinuing treatment compared to 4.8% in the 15-mg group, according to Xenon’s release. The placebo group saw just 3.2% of patients discontinue due to side effects.
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“As expected, adverse events are dose-dependent, which actually makes the 15 mg dose very attractive commercially,” the analysts wrote, also noting that azetukalner led to fewer cases of fatigue, dizziness and sleepiness than other anti-seizure meds such as SK Biopharmaceuticals’ Xcopri.
“We are very happy to announce these data for azetukalner, which exceeded expectations and, to our knowledge, show the highest placebo-adjusted efficacy ever observed in a pivotal epilepsy study,” Xenon CEO Ian Mortimer said in the release.
Investors are glowing about the results, too, bestowing Xenon with a more than 40% stock boost. Xenon shares were trading at $59.80 at 10:00 a.m. ET on Monday after previously closing at $41.94.
William Blair analysts had previously highlighted Xenon as one of their top five stock picks for 2026, citing the high potential of azetukalner. The small molecule is not alone in targeting KV7 ion channels; Biohaven’s opakalim uses the same mechanism and is currently in phase 3 trials for focal epilepsy and generalized epilepsy.
Xenon is testing azetukalner in a phase 3 generalized epilepsy trial as well, and both biotechs are also considering their candidates for depression. On that front, though, neither ion channel activator looks too hot, with both flunking their phase 2 trials in the indication.
By pursuing KV7 activators, Xenon and Biohaven are following in the footsteps of GSK and Valeant Therapeutics, who previously teamed up to make the first approved medicine in the class. That drug, ezogabine, was ultimately pulled from the market in 2017 due to the potential for vision loss. Xenon added ezogabine to its pipeline the following year, and its work with the molecule ultimately led to azetukalner.