Axsome Therapeutics Announces AXS-05 Achieves Primary Endpoint in GEMINI Phase 3 Trial in Major Depressive Disorder
GlobeNewswire • December 16, 2019
Demonstrated rapid, durable, and statistically significant improvement in depressive symptoms as measured by MADRS total score compared to placebo (p=0.002 on primary endpoint)
Statistically significant improvement at week 1 in MADRS total score compared to placebo (key secondary endpoint, p=0.007)
Statistically significant improvement versus placebo on all secondary endpoints at week 6, including remission (p<0.001), disease severity (p=0.002), functional impairment (p=0.002), and quality of life (p=0.011)
Positive results support NDA filing of AXS-05 for MDD, anticipated in 2H 2020
Potentially first-and-only, oral NMDA receptor antagonist with multimodal activity for the treatment of depression
Company to host conference call today at 8:00 AM ET
NEW YORK, Dec. 16, 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 AXS-05, a novel, oral, investigational NMDA receptor antagonist with multimodal activity, met the primary endpoint and rapidly and significantly improved symptoms of depression in the GEMINI Phase 3 trial in major depressive disorder (MDD). The GEMINI study was a randomized, double-blind, placebo-controlled, multi-center, U.S. trial, in which 327 adult patients with confirmed moderate to severe MDD were randomized to treatment with either AXS-05 (dextromethorphan/bupropion modulated delivery tablet) or placebo once daily for the first 3 days and twice daily thereafter for a total of 6 weeks.
AXS-05 met the primary endpoint by demonstrating a highly statistically significant reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo at Week 6, with mean reductions from baseline of 16.6 points for AXS-05 and 11.9 points for placebo (p=0.002). AXS-05 rapidly and durably improved depressive symptoms as compared to placebo with statistical significance on the MADRS total score demonstrated at Week 1, the earliest time point assessed, and at all time points thereafter. Rates of remission from depression (defined as MADRS =10) were statistically significantly greater for AXS-05 compared to placebo at Week 2 (p=0.013) and at every time point thereafter, being achieved by 39.5% of AXS-05 patients compared to 17.3% of placebo patients at Week 6 (p<0.001).
AXS-05 demonstrated rapid onset of action with statistically significant improvement as compared to placebo on numerous endpoints at Week 1, or only 4 days after the start of twice daily dosing. Statistically significant improvements at Week 1 were observed for MADRS total score (key secondary endpoint, p=0.007); Patient Global Impression-Improvement (PGI-I) (p=0.008); Clinical Global Impression-Severity (CGI-S) (p=0.013); Clinical Global Impression-Improvement (CGI-I) (p=0.035); Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR-16) (p=0.016); Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) (p=0.031); and other endpoints.
On all secondary endpoints including the following, AXS-05 demonstrated statistically significant improvement at Week 6 compared to placebo, reflecting increasing treatment effects over time: clinical response on the MADRS total score (defined as =50%) (p<0.001); PGI-I (p=0.007); CGI-S (p=0.002); CGI-I (p=0.016); QIDS-SR-16 (p=0.001); Sheehan Disability Scale (SDS) (p=0.002); and Q-LES-Q-SF (p=0.011).
"AXS-05 demonstrated a rapid and very clinically meaningful improvement in depressive symptoms, observed after only one week, in this large and well-controlled Phase 3 trial in major depressive disorder. Given the known challenges of conducting trials in psychiatry, it is very encouraging to see replication of Phase 2 findings in such a robust way,” said Professor Maurizio Fava, MD, Psychiatrist-in-Chief at Massachusetts General Hospital (MGH), Director of the Division of Clinical Research of the MGH Research Institute, and Associate Dean for Clinical & Translational Research at Harvard Medical School. “Clinical depression is a potentially life-threatening condition. Currently marketed antidepressants fail to provide adequate treatment response in almost two thirds of treated patients, and may take up to six to eight weeks to provide clinically meaningful response. These data suggest that AXS-05, as an oral NMDA receptor antagonist with multimodal activity, may represent a novel treatment for major depressive disorder.”
AXS-05 was well tolerated in the trial. The most commonly reported adverse events in the AXS-05 arm were dizziness, nausea, headache, diarrhea, somnolence, and dry mouth. There was one serious adverse event in the AXS-05 arm which was deemed by the investigator not to be study-drug related. The rates of discontinuation due to adverse events were low in both treatment groups (6.2% for AXS-05 and 0.6% for placebo). Treatment with AXS-05 was not associated with psychotomimetic effects or weight gain.
“We are very pleased with the compelling results of the GEMINI trial which demonstrate the potential for AXS-05 to provide significant benefits to patients living with depression, based on observed rapid and sustained antidepressant effects, resulting from its potentially first-in-class, oral NMDA receptor antagonist and multimodal mechanism of action,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “The progress of the AXS-05 clinical program in mood disorders reflects Axsome’s commitment to accelerating innovation to address serious CNS disorders. With GEMINI and the previously completed ASCEND study, the efficacy of AXS-05 in major depressive disorder has now been demonstrated in two positive well-controlled trials, enabling the filing of an NDA for AXS-05, which is anticipated in the coming year.”
AXS-05 was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of MDD in March 2019. Based on the outcome of the FDA Breakthrough Therapy meeting, Axsome believes the positive results of the GEMINI trial, along with the previously completed ASCEND trial of AXS-05 in MDD, are sufficient to support submission of a New Drug Application (NDA) for AXS-05 for the treatment of MDD. Axsome plans to file the NDA in the second half of 2020.
“Depression is a major public health concern with most patients failing to adequately respond to currently approved antidepressants,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “The potentially fatal consequences of depression highlight the need to rapidly and effectively control depressive symptoms. The positive results of the GEMINI study are significant and exciting because they bring us closer to our goal of addressing this public health need with a potentially first-in-class, rapid-acting, effective, oral, antidepressant which can be safely administered at home. With its modulation of glutamate neurotransmission, if approved, AXS-05 would represent the first mechanistically novel oral pharmacotherapy for depression in over 30 years.”