Benzinga | Dec 2, 2020 06:03AM EST

Axsome Therapeutics Announces Results From COMET-TRD Trial Of AXS-05 In Patients With Treatment Resistant Depression; Says 'Rapid and substantial improvement in depressive symptoms achieved by 44% of patients at 2 weeks, 67% at 6 weeks'

Rapid and substantial improvement in depressive symptoms achieved by 44% of patients at 2 weeks, 67% at 6 weeks (MADRS response), and sustained with long-term treatment

Rapid and substantial improvement in functioning achieved by 53% of patients at 2 weeks, 64% of patients at 6 weeks (Sheehan Disability Scale), and sustained with long-term treatment

Marked or moderate improvement in depression achieved by 49% of patients at 2 weeks, 78% of patients at 6 weeks (Clinical Global Impression), and sustained with long-term treatment

NEW YORK, Dec. 02, 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 positive results from the open-label Phase 2 COMET-TRD trial of AXS-05 in patients with treatment resistant depression (TRD). Patients treated with AXS-05 experienced rapid, substantial, and durable improvements in depressive symptoms and functional impairment that was sustained with long-term treatment. The COMET-TRD trial evaluated 70 patients who had ongoing symptoms of depression despite receiving treatment with two or more prior antidepressants during the current major depressive episode. Patients were treated with AXS-05 (45 mg dextromethorphan-105 mg bupropion modulated delivery tablet) twice daily for up to 12 months. AXS-05 is a novel, oral, investigational NMDA receptor antagonist with multimodal activity.

AXS-05 treatment resulted in rapid, substantial, and durable improvement in depressive symptoms, measured using the Montgomery-?sberg Depression Rating Scale (MADRS). Patients experienced a mean reduction from baseline in the MADRS total score of 10.4 points at Week 1, 14.7 points at Week 2, and 20.6 points at Week 6 (primary timepoint), with AXS-05 treatment. Clinical response on the MADRS (defined as ?50% reduction in total score from baseline) after treatment with AXS-05 was achieved by 21.4% of patients at Week 1, 44.1% of patients at Week 2, and 67.2% of patients at Week 6. Remission from depression (defined as MADRS ?10) after treatment with AXS-05 was achieved by 14.3% of patients at Week 1, 19.1% of patients at Week 2, and 43.8% of patients at Week 6. The improvement in depressive symptoms was sustained or increased with long-term treatment with AXS-05.

Patients experienced rapid, substantial, and durable improvement in functional impairment, as measured by the Sheehan Disability Scale (SDS), with AXS-05 treatment. The SDS is a patient-rated scale that was designed to assess functioning in work, social life, and family life, and is among the most commonly used functional impairment scales in depression clinical trials. Clinical response on the SDS (defined as a total score of ?12) after treatment with AXS-05 was achieved by 37.1% of patients at Week 1, 52.9% of patients at Week 2, and 64.1% of patients at Week 6. This improvement in functioning was maintained or increased with long-term treatment with AXS-05.

Clinicians reported rapid, substantial, and durable global improvement in depressive symptoms, measured by the Clinical Global Impression of Improvement (CGI-I) scale, in patients treated with AXS-05. Marked or moderate improvement in depressive symptoms was achieved after treatment with AXS-05 by 24.6% of patients at Week 1, 48.5% of patients at Week 2, and 78.1% of patients at Week 6. This improvement on the CGI-I was sustained or increased with long-term treatment.

"The data from the open-label COMET-TRD trial demonstrate substantial benefit in patients with depression who had failed to respond to two or more prior antidepressant treatments, a population that is known to be difficult to treat," said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. "Importantly, the rapid and sustained improvement in depressive symptoms with AXS-05 was accompanied by rapid and clinically meaningful improvement in functioning in this patient population. These results support the differentiated clinical profile of AXS-05, resulting from its novel glutamatergic mechanism of action, in the treatment of depression."

AXS-05 was well tolerated in the COMET trial. The safety profile observed was consistent with what was previously reported in controlled trials of AXS-05 in MDD, with the most commonly reported adverse events being dizziness, nausea, headache, dry mouth, and decreased appetite.

Separately, results of the Phase 2 COMET-SI trial of major depressive disorder patients with suicidal ideation are still expected before year end.

COMET-TRD Results Summary

A total of 70 treatment resistant depression (TRD) patients, defined as those who had ongoing symptoms of depression despite receiving treatment with two or more prior antidepressants during the current major depressive episode, were enrolled and treated with AXS-05 (45 mg dextromethorphan-105 mg bupropion modulated delivery tablet) twice daily for up to 12 months. Topline results are summarized below:

* The mean MADRS total score was 33.1 at baseline. The mean Sheehan Disability Scale (SDS) score was 19.0 at baseline.

* Treatment with AXS-05 was associated with a mean reduction from baseline in the MADRS total score of 10.4 points at Week 1, 14.7 points at Week 2, and 20.6 points at Week 6. Mean MADRS total score reduction from baseline after 6 and 12 months of treatment with AXS-05 was 22.9 points and 26.3 points, respectively.

* Clinical response on the MADRS (defined as ?50% reduction from baseline) after treatment with AXS-05 was achieved by 21.4% of patients at Week 1, 44.1% of patients at Week 2, and 67.2% of patients at Week 6. Clinical response on the MADRS total score after 6 and 12 months of treatment with AXS-05 was achieved by 71.7% and 90.9% of patients, respectively.

* Remission from depression (defined as MADRS ?10) after treatment with AXS-05 was achieved by 14.3% of patients at Week 1, 19.1% of patients at Week 2, and 43.8% of patients at Week 6. Remission from depression after 6 and 12 months of treatment with AXS-05 was achieved by 62.3% and 72.7% of patients, respectively.

* Marked or moderate improvement in depressive symptoms after treatment with AXS-05, assessed by the Clinical Global Impression of Improvement (CGI-I) scale, was achieved by 24.6% of patients at Week 1, 48.5% of patients at Week 2, and 78.1% of patients at Week 6. Marked or moderate improvement after 6 and 12 months of treatment with AXS05 was achieved by 79.2% and 75.0% of patients, respectively.

* Clinical response on the SDS (defined as a total score of ?12) after treatment with AXS-05, was achieved by 37.1% of patients at Week 1, 52.9% of patients at Week 2, and 64.1% of patients at Week 6. Clinical response on the SDS after 6 and 12 months of treatment with AXS-05 was achieved by 69.8% and 91.7% of patients, respectively.

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 depression. AXS-05 is also 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 depression. AXS-05 is covered by more than 93 issued U.S. and international patents providing protection out to 2040, 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.