Axsome Therapeutics Announces Publication of Pivotal ASCEND Phase 2 Trial of AXS-05 in Major Depressive Disorder in The American Journal of Psychiatry
In this study, AXS-05 (dextromethorphan-bupropion) demonstrated rapid, substantial, and statistically significant antidepressant efficacy compared with the active comparator bupropion
"Major depressive disorder is highly prevalent, debilitating and potentially life-threatening. There is an urgent need for mechanistically new treatments that are effective and well tolerated," said
"We are very pleased with the publication of the ASCEND trial results in
The ASCEND trial assessed the efficacy and safety of AXS-05 versus the active comparator bupropion in patients with MDD. A total of 80 patients with a diagnosis of moderate to severe MDD, confirmed by an independent clinical assessor, were randomized to receive AXS-05 (45 mg dextromethorphan/105 mg bupropion tablet) (n=43), or bupropion (105 mg tablet) (n=37), once daily for the first 3 days and twice daily thereafter, for a total of 6 weeks. The primary endpoint was overall treatment effect on the
In the trial, AXS-05 demonstrated rapid, substantial, and statistically significant improvement in depressive symptoms and induction of remission compared with bupropion. The mean change from baseline in MADRS score over weeks 1–6 was significantly greater with AXS-05 than with bupropion (-13.7 points vs. -8.8 points; least-squares mean difference=-4.9; p<0.001). The MADRS score change with AXS-05 was significantly greater than with bupropion at week 2 and every time point thereafter (week 6: -17.3 vs. -12.1 points; least-squares mean difference=-5.2; p=0.013). Remission rates were significantly greater with AXS-05 at week 2 and every time point thereafter (week 6: 46.5% vs. 16.2%; least-squares mean difference=30.3%; p=0.004). Most secondary outcomes favored AXS-05.
AXS-05 was generally well tolerated in the trial. The most common adverse events with AXS-05 were dizziness, nausea, dry mouth, decreased appetite, and anxiety. AXS-05 was not associated with psychotomimetic effects, weight gain, or sexual dysfunction.
The article was published today online in
AXS-05 (dextromethorphan-bupropion) is a novel, oral, patent protected, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of major depressive disorder and other central nervous system (CNS) disorders. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome's metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also known as a glutamate receptor modulator, which is a novel mechanism of action, meaning it works differently than currently approved oral therapies for major depressive disorder. The dextromethorphan component of AXS-05 is also a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is currently covered by more than 100 issued
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Chief Operating Officer
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