Axsome Therapeutics’ AXS-05 nvestigational drug meets endpoint in Phase 2 trial in major depressive disorder

Axsome Therapeutics’ AXS-05, a novel, oral, investigational NMDA receptor antagonist with multimodal activity, met the prespecified primary endpoint and significantly improved symptoms of depression in the ASCEND Phase 2 trial in major depressive disorder (MDD), the company said Monday.

AXS-05 is a novel, oral, non-competitive NMDA receptor antagonist, also known as a glutamate receptor modulator, a new mechanism of action which is thought to help enhance synaptic connections and improve the communication between brain cells in people with major depressive disorder.

“There have been no new significant pharmacological approaches in the treatment of depression over the past 30 years despite its growing contribution to the overall global burden of disease,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “If approved, AXS-05 would be the first orally administered NMDA receptor antagonist, or glutamate receptor modulator, for the treatment of depression.”

The study treated 80 adult patients with confirmed moderate to severe MDD were treated either with AXS-05 (45 mg dextromethorphan/105 mg bupropion), or the active comparator bupropion (105 mg), twice daily for 6 weeks.

AXS-05 was superior to comparator bupropion on multiple prespecified secondary endpoints. Additionally, the treatment effect observed with bupropion in the study was consistent with that observed in prior published trials.

Axsome’s CEO, Herriot Tabuteau, said: “The demonstration of a significant and rapid antidepressant effect with AXS-05, coupled with favorable safety, point to a differentiated clinical profile. These data also suggest that AXS-05 has important biological activity and support the continued development of this novel multimodal agent in MDD as well as in other neuropsychiatric indications. These results build on the positive interim futility analyses for the Phase 3 trial of AXS-05 in treatment resistant depression and the Phase 2/3 trial of AXS-05 in Alzheimer’s disease agitation. The topline results of the ongoing Phase 3 trial of AXS-05 in treatment resistant depression, anticipated later this quarter, should add to the body of clinical data with AXS-05 in mood disorders.”