Xenon Pharmaceuticals Inc. has just released positive topline results from the Phase 3 X-TOLE2 study of Azetukalner in the treatment of focal onset seizures (FOS). The study demonstrated a significant reduction in monthly FOS frequency from baseline to week 12 in both the 25 mg and 15 mg dose groups compared to placebo. The median percent change (MPC) from baseline in monthly FOS frequency with the 25 mg dose was -53.2%, compared with -10.4% for placebo. This represents a substantial improvement compared to the previously completed Phase 2B X-TOLE study, with a placebo-adjusted MPC of -42.7% in the 25 mg group in X-TOLE2, outperforming the -34.6% in the 25 mg group in X-TOLE.
The safety and tolerability profile of Azetukalner remained consistent with prior studies, with the most common treatment-emergent adverse events (TEAEs) being dizziness, headache, somnolence, and fatigue. The incidence of serious TEAEs was low and similar across treatment groups.
In addition to meeting the primary endpoint, the study also met the key secondary endpoint of responder rate 50 (RR50), with 54.8% in the 25 mg group and 37.6% in the 15 mg group experiencing at least a 50% reduction in monthly FOS frequency from baseline, compared with 20.8% in the placebo group.
The X-TOLE2 efficacy and safety results will be presented at the American Academy of Neurology (AAN) annual meeting in April.
Xenon plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for the treatment of focal onset seizures in the third quarter of 2026, and if approved, Azetukalner would be the only KV7 potassium channel opener available for the treatment of epilepsy.
The study, which included a total of 380 randomized participants, demonstrated the potential of Azetukalner to become a preferred medication for patients living with uncontrolled seizures.
These positive results represent a significant advancement in the treatment of epilepsy, a neurological condition that affects approximately three million adults in the U.S., and highlight the potential of Azetukalner to address the critical need for a new therapeutic approach.
Xenon Pharmaceuticals, a neuroscience-focused biopharmaceutical company, will be hosting a conference call and webcast to discuss the X-TOLE2 topline results.
Xenon's lead molecule, Azetukalner, is also in Phase 3 clinical trials for the treatment of major depressive disorder (MDD) and bipolar depression (BPD), and the company is advancing an early-stage portfolio of multiple promising potassium and sodium channel modulators for the potential treatment of pain. Today the company's shares have moved -1.86% to a price of $39.98. If you want to know more, read the company's complete 8-K report here.
