Positive Results for Dextromethorphan-Bupropion ASCEND Phase 2 Clinical Trial

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Axsome Therapeutics announced the publication of the results from the pivotal ASCEND phase 2 clinical trial of dextromethorphan-bupropion (AXS-05) in major depressive disorder (MDD).¹ Dextromethorphan-bupropion is an oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal activity.

“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 coauthor 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.”²

The trial assessed the efficacy and safety of dextromethorphan-bupropion versus bupropion in 80 participants with moderate to severe MDD. Participants were randomized to receive dextromethorphan-bupropion (45 mg dextromethorphan/105 mg bupropion tablet) (n=43), or bupropion (105 mg tablet) (n=37), once daily for the first 3 days and then twice daily for the following 6 weeks. The primary endpoint was overall treatment effect on the Montgomery-Åsberg Depression Rating Scale (MADRS) score.

Dextromethorphan-bupropion demonstrated rapid, statistically significant improvement in depressive symptoms and remission compared with bupropion. The mean change from baseline in MADRS score over weeks 1 to 6 was significantly better with dextromethorphan-bupropion than with bupropion (-13.7 points vs. -8.8 points; least-squares mean difference=-4.9; p<0.001). Remission rates were significantly greater with dextromethorphan-bupropion at week 2 and every time point thereafter (week 6: 46.5% vs 16.2%; least-squares mean difference=30.3%; p=0.004).

“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 world,” 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.”²

AXS-05 was generally well tolerated in the trial. Common adverse effects included dizziness, nausea, dry mouth, decreased appetite, and anxiety. AXS-05 was not associated with psychotomimetic effects, weight gain, or sexual dysfunction.

The article, “Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized, Double-Blind, Controlled Trial,” can be found in The American Journal of Psychiatry.¹

References

1. Tabuteau H, Jones A, Anderson A, et al. Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry. 2022;appiajp21080800. Online ahead of print.

2. Axsome Therapeutics announces publication of pivotal ascend phase 2 trial of AXS-05 in major depressive disorder in the American Journal of Psychiatry. PRNewswire. News release. May 18, 2022. Accessed May 19, 2022. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-publication-pivotal-ascend-phase-2