In this study, AXS-05 (dextromethorphan-bupropion) demonstrated rapid, substantial, and statistically significant antidepressant efficacy compared with the active comparator bupropion
NEW YORK, May 18, 2022 /PRNewswire/ -- Axsome Therapeutics, Inc. (NASDAQ:AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced the publication of the results from the pivotal ASCEND Phase 2 clinical trial of AXS-05 (dextromethorphan-bupropion) in major depressive disorder (MDD). AXS-05 is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal activity. The article, "Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized, Double-Blind, Controlled Trial," was published today in The American Journal of Psychiatry and is available in full here.
"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 Dan Iosifescu, MD, Professor of Psychiatry at the New York University School of Medicine, Director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research, and co-author of the publication. "Due to its novel mechanism of action targeting glutamate and sigma-1 receptors, and to its robust antidepressant efficacy demonstrated in this study, AXS-05 has the potential to become an important and very useful new treatment for patients with major depressive disorder."
"We are very pleased with the publication of the ASCEND trial results in The American Journal of Psychiatry, the most widely read psychiatric journal in the world1," said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. "ASCEND is one of the pivotal efficacy trials that forms the basis of our NDA for AXS-05 in depression, which is currently under review by the FDA. Axsome is positioned to move expeditiously to make this product available to patients as quickly as possible, should it be approved."
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 Montgomery-Åsberg Depression Rating Scale (MADRS) score (average of the change from baseline for weeks 1–6).
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 The American Journal of Psychiatry in advance of the corresponding upcoming print issue.