AXS-05 also showed superiority to placebo in safety.
New data indicates a positive future for AXS-05 (dextromethorphan-bupropion) as a potential treatment for patients with major depressive disorder.
The drug, developed by Axsome Therapeutics, is a novel, oral investigational N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal activity.
The results from the GEMINI phase 3 clinical trial show AXS-05 showed rapid, substantial, and statistically significant antidepressant efficacy compared to placebo.
In the 327 patient study, the investigators examined individuals with a confirmed diagnosis of moderate to severe MDD. Each patient was randomized to receive either 45 mg dextromethorphan/105 mg bupropion tablet (n = 163) or placebo (n = 164) once daily for 3 days, followed by twice daily after for a total of 6 weeks.
The investigators sought primary endpoints of the change on the Monthomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 6.
They also looked at key primary endpoints of the change from baseline in the MADRS total score at week 1, change from baseline in the MADRS total score at week 2, remission on the MADRS at week 2, and clinical response on the MADRS at week 6.
The investigators found the change from baseline in MADRS scores to week 6 was significantly greater in the AXS-05 group compared to placebo (-15.9 points vs. -12.0 points; least-squares mean difference = -3.87; P = 0.002) and the MADRS score change in the treatment cohort was significantly greater than placebo at week 1 and at every other timepoint (week 1: -7.20 vs. -4.97 points; least-squares mean difference=-2.23; P = 0.007).
The remission rates were also significantly greater in the treatment group at week 2 and every other timepoint (week 6: 39.5% vs. 17.3%; treatment difference = 22.2%; P <0.001).
For secondary outcomes, most favored AXS-05 over placebo.
For safety, the treatment was well-tolerated, with the most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth. The treatment was also not associated with psychotomimetic effects, weight gain, or increased sexual dysfunction.
“The results published in The Journal of Clinical Psychiatry are consistent with strong and rapid antidepressant effects, and with a favorable safety profile with AXS-05,” said Maurizio Fava, MD, Psychiatrist-In-Chief, Department of Psychiatry, Massachusetts General Hospital, in a statement. “Depression is a difficult-to-treat condition with potentially devastating consequences for patients and their families. Based on these results and its novel oral NMDA antagonist mechanism, AXS-05 may represent an important new treatment option for patients with depression.”
The treatment has been granted FDA Breakthrough Therapy designation for both MDD and Alzheimer disease agitation. There is also a New Drug Application (NDA) for MDD.