Full Press Release Details
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
Rapid, durable, and statistically significant
improvement demonstrated in patient-reported depressive symptoms, as measured by the QIDS-SR-16 total score compared to placebo
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
NEW YORK, September 14, 2020 (Globe
Newswire) - Axsome Therapeutics, Inc. (NASDAQ: AXSM), a 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, rapidly and significantly improved patient-reported outcomes of depression in patients with
major depressive disorder (MDD) in the GEMINI Phase 3 trial. These findings were presented at the 33rd Congress of the
European College of Neuropsychopharmacology (ECNP), being held virtually September 12-15.
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. Two patient-reported outcomes (PROs) for depression were assessed in this trial:
the Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR-16), and the Patient Global Impression of Improvement (PGI-I)
for depression. The QIDS-SR-16 is a well-established PRO that was the primary outcome measure in the landmark NIH-funded STAR*D
trial of antidepressant treatments3. A PRO is a report of the status of a patient's health condition that comes
directly from the patient, without interpretation of the patient's response by a clinician or anyone else. PROs therefore
provide a measurement of patients' perception of their own depression status as a result of an intervention. The PROs complement
the clinician-rated measures, such as the Montgomery- sberg Depression Rating Scale (MADRS), that were also assessed in the
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 U.S. and international patents providing protection out to 2034, and Axsome maintains worldwide rights.
AXS-05 was granted Breakthrough Therapy
designation by the U.S. Food and Drug Administration (FDA) for the treatment of MDD in March 2019.
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 U.S. A total of 327 patients with a confirmed diagnosis of moderate to severe
MDD were randomized in a 1:1 ratio to receive AXS-05 (45 mg dextromethorphan/105 mg bupropion) (n=163), or placebo (n=164), twice
daily for 6 weeks. The primary endpoint of the study was the change from baseline in the total score of the Montgomery- sberg
Depression Rating Scale (MADRS), a clinician-rated scale, at Week 6. Two patient-reported outcomes (PROs) for depression were also
assessed: the Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR-16), and the Patient Global Impression of Improvement
(PGI-I) for depression. The mean MADRS total scores at baseline were 33.6 for the AXS-05 group and 33.2 for the placebo group.
The mean QIDS-SR-16 total scores at baseline were 16.2 for the AXS-05 group and 15.8 for the placebo group. P-values were calculated
based on least square mean estimates.
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 National Institutes of Health, an estimated 7.1% of U.S.
adults, or approximately 17 million, experience MDD each year1. According to the World Health Organization (WHO), depression
is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease2. Nearly
two thirds of diagnosed and treated patients do not experience adequate treatment response with currently available first-line
therapy3, highlighting the need for additional therapies with new mechanisms of action. The majority of initial failures
also fail second-line treatment. Patients diagnosed with MDD are defined as having treatment resistant depression (TRD) if they
have failed to respond to two or more antidepressant therapies.
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