Xenon Presents New Long-Term Azetukalner Data from X-TOLE OLE Study at AES 2024

Xenon Pharmaceuticals Inc., a biopharmaceutical company dedicated to developing therapeutics for neurological conditions, has announced new data from its ongoing X-TOLE open-label extension (OLE) study of azetukalner. The data, presented at the American Epilepsy Society Annual Meeting 2024, underscores the long-term efficacy and safety of azetukalner in patients with focal onset seizures (FOS).

Dr. Christopher Kenney, Chief Medical Officer of Xenon, highlighted the significance of the findings, noting that approximately one-third of patients on azetukalner for at least 36 months achieved complete seizure freedom for a year or longer. This result demonstrates the potential for azetukalner to significantly improve the quality of life for epilepsy patients. The study also showed an 85% reduction in seizure frequency at month 36, maintaining a consistent safety profile indicative of the drug’s long-term tolerability.

Dr. Kenney emphasized the persistent need for effective and well-tolerated epilepsy treatments, particularly for patients who continue to suffer from focal seizures despite being on multiple anti-seizure medications. The ongoing development of azetukalner, combined with supportive data from the X-TOLE study, suggests that this medication could be transformative in epilepsy management.

Interim data from the X-TOLE OLE, where participants received a daily dose of 20 mg of azetukalner, showed sustained seizure frequency reductions. Monthly median percent change (MPC) reductions in FOS frequency ranged from 61% to 82% through month 24, maintaining at 85% at month 36. Patients on 1 to 2 anti-seizure medications at baseline exhibited higher MPC reductions compared to those on 3 medications.

The study also revealed that 32.7% of patients treated for more than 36 months achieved seizure freedom for at least 12 months. Azetukalner has demonstrated consistent tolerability with adverse events in line with previous results, and no new safety concerns were identified. Retention rates for the study were 66% at 12 months, 60% at 24 months, and 52% at 36 months.

Ian Mortimer, President and CEO of Xenon, discussed the cumulative patient years of azetukalner exposure and the substantial clinical experience gathered. He mentioned the importance of understanding the mental health burden and comorbidities associated with focal onset seizures, emphasizing the need for personalized treatment to improve patient outcomes. The company also presented new pre-clinical data showing that a Nav1.1 potentiator provided protection against spontaneous seizures and sudden unexpected death in epilepsy (SUDEP) in a Dravet syndrome model.

The poster presentations at the conference discussed the mental health burden of epilepsy, noting that patients with FOS experience significant mental health issues, including depression and anxiety. A high percentage of these patients reported mood symptoms, often more severe than those diagnosed by physicians, suggesting an under-recognition of mental health issues in this population.

Additionally, a literature review highlighted the greater disease burden in FOS patients with comorbid conditions, pointing to the need for targeted treatments. Another study on Nav1.1 potentiators showed their potential to modulate brain rhythms and improve motor function in a Dravet mouse model, suggesting these compounds could offer new therapeutic options.

Overall, the new data from Xenon Pharmaceuticals reinforces the potential of azetukalner as a promising treatment for epilepsy, with significant implications for improving patient quality of life through sustained seizure reduction and freedom. The company continues to advance its clinical programs, aiming to address substantial unmet needs in epilepsy and other neurological conditions.