Axsome Therapeutics Presents New Data from GEMINI Phase 3 Trial with AXS-05 Demonstrating Rapid and Significant Improvements in Patient-Reported Outcomes in Major Depressive Disorder
Rapid, durable, and statistically significant improvement demonstrated in patient-reported depressive symptoms, as measured by the QIDS-SR-16 total score compared to placebo (p=0.001)
Clinical response on the QIDS-SR-16 demonstrated in 53% of patients with AXS-05 compared to 33% for placebo (p<0.001)
Significant improvement on the PGI-I demonstrated, with 47% of patients reporting their depression being “very much” or “much” improved with AXS-05 versus 31% with placebo (p=0.007)
Statistically significant improvement at week 1 versus placebo in QIDS-SR-16 total score (p=0.016), and PGI-I (p=0.008), compared to placebo
Potentially first-and-only, oral NMDA receptor antagonist with multimodal activity for the treatment of depression
The GEMINI study was a randomized, double-blind, placebo-controlled, multi-center,
AXS-05 demonstrated a highly statistically significant reduction in patient-reported depressive symptoms compared to placebo at Week 6, with mean reductions from baseline in the QIDS-SR-16 total score of 7.8 points for AXS-05 and 5.4 points for placebo, representing 48% and 34% reductions from baseline, respectively (p=0.001). AXS-05 rapidly and durably improved patient-reported depressive symptoms as compared to placebo with statistical significance on the QIDS-SR-16 total score demonstrated at Week 1 (p=0.016), the earliest time point assessed, at Week 2 (p<0.001), and at all time points thereafter. Clinical response on the QIDS-SR-16 (defined as ≥50% improvement) was statistically significantly greater for AXS-05 compared to placebo at Week 1 (p=0.048), at Week 2 (p<0.001), and at every time point thereafter, being achieved by 53.4% of AXS-05 patients compared to 32.9% of placebo patients at Week 6 (p<0.001).
On the patient-reported global measure of depression, the PGI-I, AXS-05 demonstrated highly statistically significant improvements as compared to placebo, with 47.2% of patients treated with AXS-05 reporting that their depression was “very much” or “much” improved compared to 31.3% of placebo patients at Week 6 (p=0.007). Improvement on the PGI-I with AXS-05 as compared to placebo was rapid and durable with statistical significance demonstrated at Week 1 (p=0.008) and at all time points thereafter.
The results on these patient-reported measures are consistent with those observed with the corresponding clinician-rated scales, the MADRS and the Clinical Global Impression of Improvement (CGI-I). As previously reported, AXS-05 met the primary endpoint in the GEMINI trial by demonstrating a highly statistically significant reduction in the 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 also demonstrated statistically significant improvement at Week 6 compared to placebo on the CGI-I (p=0.016). Rapid improvement in depressive symptoms was also demonstrated on these clinician-rated scales, with statistically significant improvements starting at Week 1 and every timepoint thereafter (MADRS p=0.007, CGI-I p=0.035).
"The positive results with AXS-05 on patient-reported outcomes are significant since depression, by its very nature, involves symptoms that may be unobservable and known only to the patient,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “These patient-reported outcomes mirror the results previously reported with clinician-rated scales and confirm the rapid and substantial antidepressant effects of AXS-05. With its novel oral glutamatergic mechanism targeting NMDA, AXS-05 may help to address the needs of the many patients living with depression, about two thirds of whom fail to respond to currently available antidepressants.”
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. Treatment with AXS-05 was not associated with psychotomimetic effects or weight gain.
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. In addition, AXS-05 is a sigma-1 receptor agonist; enhances brain levels of serotonin, noradrenaline, and dopamine, which are key neurotransmitters involved in the regulation of mood; and displays anti-inflammatory properties, which may be relevant to treating MDD. The multimodal actions of AXS-05 may be complementary and synergistic for the treatment of this biologically-based condition. AXS-05 is covered by 45 issued
AXS-05 was granted Breakthrough Therapy designation by the
About the GEMINI Trial
GEMINI (Glutamatergic and Monoaminergic Modulation in Depression) was a Phase 3, randomized, double-blind, multicenter, placebo-controlled trial of AXS-05 in patients with major depressive disorder (MDD) conducted in the
About the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16)
The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) is a well-established, 16-item, validated rating scale used to provide a patient-reported assessment of depression. The scale is used to rate the severity of depression as assessed by the patient across nine question domains comprising sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, changes in appetite or weight, and psychomotor agitation or retardation. The total score ranges from 0 to 27 with higher scores indicating more severe depression.
About Major Depressive Disorder (MDD)
Major depressive disorder (MDD) is a debilitating, chronic, biologically-based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, and which impairs social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. According to the
AXS-05 is a novel, oral, patent-protected, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of major depressive disorder and other central nervous system (CNS) disorders. AXS-05 consists of a proprietary formulation and dose 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 approved therapies for major depressive disorder. 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 45 issued
3. Rush AJ, et al. (2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).
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