Axsome Therapeutics Announces AXS-05 Achieves Primary Endpoint in Phase 2 Trial in Smoking Cessation
GlobeNewswire•April 15, 2019
Demonstrated statistically significant reduction in daily smoking compared to active comparator (p=0.0016)
Trial conducted in collaboration with Duke University
NEW YORK, April 15, 2019 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (AXSM), a clinical-stage biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today announced that Duke University has completed its topline analysis of the Phase 2 trial of AXS-05 for smoking cessation treatment. The analysis showed that AXS-05 met the prespecified primary endpoint and significantly reduced daily smoking as compared to the active comparator bupropion. The trial was conducted at the Duke Center for Smoking Cessation under a research collaboration between Axsome and Duke University. The Phase 2 study was a randomized, double-blind, active-controlled trial, in which 58 adult smokers were treated either with AXS-05 (45 mg dextromethorphan/105 mg bupropion), or the active comparator bupropion (105 mg), twice daily, and assessed over a 3-week period.
Treatment with AXS-05 resulted in a 25% greater reduction in the average number of cigarettes smoked per day over the 3-week period, the prespecified primary endpoint, as compared to bupropion (average reductions of 8.49 and 6.79 cigarettes per day for AXS-05 and bupropion, respectively, p=0.0016). Consistent with this finding, a greater proportion of smokers receiving AXS-05 experienced a more than 50% reduction in expired carbon monoxide levels, a biochemical marker of smoking intensity, as compared to those treated with bupropion (52.0% for AXS-05 versus 30.4% for bupropion, p=0.15). In addition, subjects who took AXS-05 as prescribed on a given day smoked 1.0 fewer cigarette on the day of medication use (p=0.026) and 1.2 fewer cigarettes on the following day (p=0.008) as compared to those who missed one or both doses.
“The findings in this trial are notable because AXS-05 was compared to bupropion, an approved treatment for smoking cessation.” said James Davis, MD, 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. Reduction in ad-lib smoking was selected as the primary endpoint in this trial, because it has been shown to correlate with smoking abstinence. I look forward to the continued evaluation of AXS-05 as a smoking cessation treatment.”
Medication adherence was similar between the study arms for both the morning dose (97.1% for AXS-05 and 96.6% for bupropion) and the evening dose (76.3% for AXS-05 and 79.4% for bupropion). In the study, AXS-05 was safe and well tolerated with no serious adverse events. The most commonly reported side effects were headache, dry mouth, and insomnia/vivid dreams, with similar incidences in both treatment arms.
“The topline results of this Phase 2 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,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “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.”
“Smoking is widely recognized as the leading cause of preventable death and affects approximately 40 million adults in the U.S. alone,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “Unfortunately, the vast majority of smokers who attempt to quit fail to do so highlighting the need for new approaches. We look forward to learning more about the potential of the novel mechanisms of action of AXS-05 to address this condition.”
AXS-05 is a novel, oral, NMDA receptor antagonist, also known as a glutamate receptor modulator, a potentially new mechanism of action for smoking cessation treatment. AXS-05 consists of dextromethorphan and bupropion, and utilizes Axsome’s metabolic inhibition technology to increase the bioavailability of dextromethorphan. Both components of AXS-05 are nicotinic acetylcholine receptor antagonists, a mechanism that is relevant to nicotine dependence.
About the Phase 2 Trial
The trial was a Phase 2, randomized, double-blind, active-controlled study to evaluate the efficacy and safety of AXS-05 for smoking cessation treatment. A total of 58 smokers were randomized in a 1:1 ratio to receive either AXS-05 (45 mg dextromethorphan/105 mg bupropion) (n=31), or bupropion (105 mg) (n=27), twice daily, and assessed over a 3-week period. Enrolled subjects were daily smokers using 10 or more cigarettes per day. The average number of cigarettes smoked per day at baseline was 20 for AXS-05 and 17 for the bupropion treatment groups. The primary outcome measure was the change in smoking intensity, measured using the number of cigarettes smoked per day, assessed via daily smoking diaries. The trial was conducted at the Duke Center for Smoking Cessation.
Nearly 40 million American adults smoke and around 70% report that they want to quit. Tobacco use results in approximately 500,000 premature deaths each year in the U.S., according to the Centers for Disease Control and Prevention. Smoking is the single largest cause of premature deaths worldwide accounting for an estimated almost 20% of all deaths in developed countries . Direct health care and lost productivity costs as a result of smoking total nearly $300 billion a year in the U.S. alone. It is estimated that only 3 to 5% of cigarette smokers who attempt to quit without assistance are successful for 6 to 12 months, and that relapse rates remain above 80% even with current treatments .
AXS-05 is a novel, oral, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of central nervous system (CNS) disorders. AXS-05 consists of dextromethorphan and bupropion and utilizes Axsome’s metabolic inhibition technology. The dextromethorphan component of AXS-05 is a non-competitive 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 available therapies for depression. The dextromethorphan component of AXS-05 is also a sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, and inhibitor of the serotonin and norepinephrine transporters. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 is covered by more than 30 issued U.S. and international patents which provide protection out to 2034. AXS-05 is not approved by the FDA.