Axsome’s AXS-05 Helps Patients Quit Smoking Significantly in Phase II Trial



Axsome Therapeutics, based in New York City, announced that its AXS-05 met its primary endpoint for smoking cessation treatment. The drug significantly reduced daily smoking compared to patients on bupropion.

The trial, as well as the topline analysis, was conducted at Duke University’s Duke Center for Smoking Cessation. Treatment with the drug resulted in a 25% greater decrease in the average number of cigarettes smoked each day over a 3-week period. For patients receiving AXS-05, the average reduction was 8.49 cigarettes per day, while it was 6.79 for patients receiving bupropion.

In addition, patients receiving AXS-05 showed a more than 50% reduction in expired carbon monoxide levels. This is a biochemical marker of smoking intensity. For patients receiving bupropion, the expired carbon monoxide levels decreased by 30.4%.

“The findings in this trial are notable because AXS-05 was compared to bupropion, an approved treatment for smoking cessation,” stated James Davis, medical director of the Duke Center for Smoking Cessation and principal investigator of the trial. “The improvement of AXS-05 over bupropion observed in this trial is similar in magnitude to the improvement over placebo reported for the approved smoking cessation treatment varenicline in studies with a similar design.”

Bupropion is prescribed as a treatment for both smoking cessation and depression. It is marketed under several brand names, including Wellbutrin XL, Zyban, and Forfivo. Varenicline is marketed as Chantix by Pfizer.

AXS-05 is a novel, oral NMDA receptor antagonist. It is being developed for the treatment of central nervous system (CNS) disorders. It is made up of dextromethorphan and bupropion using Axsome’s metabolic inhibition technology.

On March 27, the U.S. Food and Drug Administration (FDA) granted AXS-05 Breakthrough Therapy designation for the treatment of major depressive disorder (MDD). This designation was supported by data from the Phase II ASCEND trial, which looked at 80 patients with confirmed moderate to severe MDD, who received AXS-05 or bupropion. Those receiving AXS-05 showed a fast and statistically significant decrease in depression symptoms compared to those on bupropion.

AXS-05 is also being investigated in the clinic for Alzheimer’s disease and treatment-resistant depression, both of which are in ongoing Phase III clinical trials.

The company also has several other compounds in the clinic. These include AXS-08 for migraine, currently in a Phase III trial; AXS-12 for narcolepsy, now in Phase II; and AXS-09 for CNS disorders, wrapping Phase I.

In the Phase II smoking cessation trial, 48 smokers were randomized 1:1 to either receive AXS-05 or bupropion. They were given the respective drugs twice a day and evaluated over three weeks. The smokers enrolled used 10 or more cigarettes daily. The average number of cigarettes smoked daily at baseline was 20 for the AXS-05 group and 17 for the bupropion group.

Drug adherence between the two groups was similar. AXS-05 was safe and well tolerated and there were no serious adverse events. The most common side effects were headache, dry mouth, and insomnia and vivid dreams. The incidences of these side effects were similar in both treatment groups.

“The topline results of this Phase II trial in smoking cessation add to the growing body of clinical data demonstrating biologic activity for AXS-05 in different areas of unmet medical need including major depressive disorder,” stated Herriot Tauteau, Axsome’s chief executive officer. “We would like to thank the team at the Duke Center for Smoking Cessation for their collaboration with Axsome and for the execution of this important trial. We look forward to continuing to analyze these results with the team at Duke and to determining the next steps for this program.”