Xenon Pharmaceuticals Announces Topline Results from Phase 2 Proof-of-Concept X-NOVA Clinical Trial of XEN1101 in Major Depressive Disorder (MDD)

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VANCOUVER, British Columbia, Nov. 27, 2023 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a neurology-focused biopharmaceutical company, today reported topline results from the randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept X-NOVA clinical trial, which evaluated the clinical efficacy, safety, and tolerability of 10 mg and 20 mg of XEN1101 in 168 patients with moderate to severe major depressive disorder, or MDD.

Summary of Efficacy Data

• The primary endpoint of the study was a change in the Montgomery-Åsberg Depression Rating Scale, or MADRS, at week 6. The mean reduction was 13.90 in the placebo group, 15.61 in the XEN1101 10 mg group and 16.94 in the XEN1101 20 mg group. A clear dose response and a clinically meaningful, but not statistically significant, 3.04 difference between placebo and the XEN1101 20 mg group (p=0.135) was observed.
• Statistical significance was achieved on the pre-specified endpoint of the Hamilton Depression Rating Scale, or HAM-D17, at week 6 with a mean reduction of 10.18 in the placebo group and 13.26 in the XEN1101 20 mg group (p=0.042).
• Statistical significance was achieved on the key secondary endpoint of a change in the Snaith-Hamilton Pleasure Scale, or SHAPS, measuring anhedonia at week 6 with a reduction of 5.30 in the placebo group and 7.77 in the XEN1101 20 mg group (p=0.046).
• Statistical significance was achieved in MADRS at week 1 with a mean reduction of 4.88 in the placebo group and 7.54 in the XEN1101 20 mg group (p=0.047) demonstrating early onset of efficacy.
• Statistical significance was achieved in reporting of at least minimally improved symptoms of depression as assessed by physicians using the Clinical Global Impression of Improvement (CGI-I) (p=0.004) in the XEN1101 20 mg group compared to placebo.

Summary of Safety and Tolerability Data

• XEN1101 was well tolerated with similar rates of adverse events reported across all treatment arms.
• The most commonly reported treatment-emergent adverse events (TEAEs) in the XEN1101 20 mg group included dizziness (17.9%), somnolence (10.7%), headache (8.9%) and disturbance in attention (8.9%), as compared to the placebo group which reported dizziness (7.3%), somnolence (1.8%), headache (12.7%) and disturbance in attention (0%).
• Rates of discontinuation were similar across all treatment arms and rates of discontinuation due to TEAEs were low with three patients in the XEN1101 20 mg group (5.4%), as compared to two patients in the placebo group (3.6%).
• No serious adverse events (SAEs) were reported in the two XEN1101 treatment groups and there were two patients (3.6%) in the placebo group who experienced a treatment-emergent SAE.
• XEN1101 was not associated with clinically meaningful weight gain or sexual dysfunction.

Dr. Christopher Kenney, Xenon’s Chief Medical Officer, stated, “We are encouraged by the data we have generated with XEN1101 in this proof-of-concept study where we see clinically meaningful, dose-dependent drug activity and early onset of efficacy in depression. Importantly, XEN1101 was well tolerated in this patient population, with a low incidence of treatment-emergent adverse events, and no serious adverse events in either dose group.  These data also support our belief that XEN1101, through its unique Kv7 mechanism of action, has the potential to play an important role in addressing anhedonia, a common co-morbidity in depression. Overall, there continues to be a strong need for new treatment options for MDD, and we believe XEN1101 has attractive qualities such as a novel mechanism, early onset of action and an overall favorable tolerability and safety profile.”