Xenon Pharmaceuticals (XENE) has submitted a New Drug Application (NDA) to the FDA for azetukalner, its lead investigational therapy for treating focal onset seizures (FOS) in epilepsy. If approved, this would mark the company’s first commercial product. The application was supported by positive results from two global studies: phase IIb X-TOLE and phase III X-TOLE2, which indicated a statistically significant reduction in monthly seizure frequency compared to placebo across all doses of azetukalner. The drug was generally well-tolerated, showcasing a consistent safety profile across the trials.

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Xenon is actively advancing its azetukalner epilepsy program. Following the data release from the X-TOLE2 trial in March, the phase III X-TOLE3 study is currently enrolling patients. This study aims to support potential regulatory submissions for azetukalner for FOS in markets outside the U.S., with patient enrollment expected to conclude in 2026. Additionally, Xenon is conducting a phase III X-ACKT study to evaluate azetukalner for primary generalized tonic-clonic seizures, with enrollment ongoing.

However, Xenon has temporarily paused the enrollment of new patients in its late-stage clinical studies evaluating azetukalner for major depressive disorder (MDD) and bipolar depression (BPD). This decision was made following the identification of neuropsychiatric adverse events in these trials. The X-NOVA2 and X-NOVA3 studies are focused on MDD, while the X-CEED study targets patients with BPD. Patients already enrolled will continue receiving treatment. According to the company, the observed side effects align with azetukalner's known safety profile but were not present in an earlier phase II study for MDD. The pause, deemed precautionary, was made in conjunction with the data safety monitoring board, and the company is evaluating potential dose adjustments to mitigate these side effects. Notably, this decision does not affect the ongoing epilepsy studies.

The enrollment pause in the MDD and BPD programs has raised investor concerns, leading to a 27% drop in XENE shares during premarket trading. Year to date, however, the stock has risen by 28%, in contrast to the industry's growth of 8.7%.