In this study, AXS-05
(dextromethorphan-bupropion) demonstrated rapid, substantial, and
statistically significant antidepressant efficacy compared with the
active comparator bupropion
NEW
YORK, May 18, 2022 /PRNewswire/ -- Axsome
Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company
developing and delivering novel therapies for the management of
central nervous system (CNS) disorders, today announced the
publication of the results from the pivotal ASCEND Phase 2 clinical
trial of AXS-05 (dextromethorphan-bupropion) in major depressive
disorder (MDD). AXS-05 is a novel, oral, investigational
N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal
activity. The article, "Effect of AXS-05
(Dextromethorphan-Bupropion) in Major Depressive Disorder: A
Randomized, Double-Blind, Controlled Trial," was published today in
The American Journal of Psychiatry and is available in full
here.
"Major depressive disorder is highly prevalent, debilitating and
potentially life-threatening. There is an urgent need for
mechanistically new treatments that are effective and well
tolerated," said Dan Iosifescu, MD,
Professor of Psychiatry at the New York
University School of Medicine, Director of the Clinical
Research Division at the Nathan Kline Institute for Psychiatric
Research, and co-author of the publication. "Due to its novel
mechanism of action targeting glutamate and sigma-1 receptors, and
to its robust antidepressant efficacy demonstrated in this study,
AXS-05 has the potential to become an important and very useful new
treatment for patients with major depressive disorder."
"We are very pleased with the publication of the ASCEND trial
results in The American Journal of Psychiatry, the most
widely read psychiatric journal in the world1," said
Herriot Tabuteau, MD, Chief
Executive Officer of Axsome. "ASCEND is one of the pivotal efficacy
trials that forms the basis of our NDA for AXS-05 in depression,
which is currently under review by the FDA. Axsome is positioned to
move expeditiously to make this product available to patients as
quickly as possible, should it be approved."
The ASCEND trial assessed the efficacy and safety of AXS-05
versus the active comparator bupropion in patients with MDD. A
total of 80 patients with a diagnosis of moderate to severe MDD,
confirmed by an independent clinical assessor, were randomized to
receive AXS-05 (45 mg dextromethorphan/105 mg bupropion tablet)
(n=43), or bupropion (105 mg tablet) (n=37), once daily for the
first 3 days and twice daily thereafter, for a total of 6 weeks.
The primary endpoint was overall treatment effect on the
Montgomery-Åsberg Depression
Rating Scale (MADRS) score (average of the change from baseline for
weeks 1–6).
In the trial, AXS-05 demonstrated rapid, substantial, and
statistically significant improvement in depressive symptoms and
induction of remission compared with bupropion. The mean change
from baseline in MADRS score over weeks 1–6 was significantly
greater with AXS-05 than with bupropion (-13.7 points vs. -8.8
points; least-squares mean difference=-4.9; p<0.001). The MADRS
score change with AXS-05 was significantly greater than with
bupropion at week 2 and every time point thereafter (week 6: -17.3
vs. -12.1 points; least-squares mean difference=-5.2; p=0.013).
Remission rates were significantly greater with AXS-05 at week 2
and every time point thereafter (week 6: 46.5% vs. 16.2%;
least-squares mean difference=30.3%; p=0.004). Most secondary
outcomes favored AXS-05.
AXS-05 was generally well tolerated in the trial. The most
common adverse events with AXS-05 were dizziness, nausea, dry
mouth, decreased appetite, and anxiety. AXS-05 was not associated
with psychotomimetic effects, weight gain, or sexual
dysfunction.
The article was published today online in The American
Journal of Psychiatry in advance of the corresponding upcoming
print issue.
About AXS-05
AXS-05 (dextromethorphan-bupropion) 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
utilizes a proprietary formulation and dose of dextromethorphan and
bupropion, and Axsome's metabolic inhibition technology, to
modulate the delivery of the components. The dextromethorphan
component of AXS-05 is an uncompetitive 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 oral therapies for major depressive
disorder. The dextromethorphan component of AXS-05 is also a
sigma-1 receptor agonist. The bupropion component of AXS-05 serves
to increase the bioavailability of dextromethorphan, and is a
norepinephrine and dopamine reuptake inhibitor. AXS-05 is currently
covered by more than 100 issued U.S. and international patents,
with expiration dates out to 2040. AXS-05 has been granted FDA
Breakthrough Therapy designations for the treatment of MDD and for
the treatment of Alzheimer's disease agitation. A new drug
application (NDA) for AXS-05 for the treatment of major depressive
disorder is under review by the FDA. AXS-05 is not approved by the
FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company
developing and delivering novel therapies for CNS conditions that
have limited treatment options. Through development of therapeutic
options with novel mechanisms of action, we are transforming the
approach to treating CNS conditions. At Axsome, we are committed to
developing products that meaningfully improve the lives of patients
and provide new therapeutic options for physicians. For more
information, please visit the Company's website at axsome.com. The
Company may occasionally disseminate material, nonpublic
information on the company website.
Forward Looking Statements
Certain matters discussed in this press release are
"forward-looking statements". We may, in some cases, use terms such
as "predicts," "believes," "potential," "continue," "estimates,"
"anticipates," "expects," "plans," "intends," "may," "could,"
"might," "will," "should" or other words that convey uncertainty of
future events or outcomes to identify these forward-looking
statements. In particular, the Company's statements regarding
trends and potential future results are examples of such
forward-looking statements. The forward-looking statements include
risks and uncertainties, including, but not limited to, the
continued commercial success of our newly acquired Sunosi product;
the success, timing and cost of our ongoing clinical trials and
anticipated clinical trials for our current product candidates,
including statements regarding the timing of initiation, pace of
enrollment and completion of the trials (including our ability to
fully fund our disclosed clinical trials, which assumes no material
changes to our currently projected expenses), futility analyses and
receipt of interim results, which are not necessarily indicative of
the final results of our ongoing clinical trials, and the number or
type of studies or nature of results necessary to support the
filing of an NDA for any of our current product candidates; our
ability to fund additional clinical trials to continue the
advancement of our product candidates; the timing of and our
ability to obtain and maintain FDA or other regulatory authority
approval of, or other action with respect to, our product
candidates (including, but not limited to, whether potential filing
issues or issues identified by FDA during the substantive review
may impact the potential approvability of the Company's NDA
submission for AXS-05 in MDD or the timing of such approval;
whether issues identified by FDA in the complete response letter
may impact the potential approvability of the Company's NDA for
AXS-07 for the acute treatment of migraine in adults with or
without aura, pursuant to our special protocol assessment for the
MOMENTUM clinical trial; the potential for the ASCEND clinical
trial, combined with the GEMINI clinical trial results, to provide
a basis for approval of AXS-05 for the treatment of major
depressive disorder and accelerate its development timeline and
commercial path to patients; the Company's ability to successfully
defend its intellectual property or obtain the necessary licenses
at a cost acceptable to the Company, if at all; the successful
implementation of the Company's research and development programs
and collaborations; the success of the Company's license
agreements; the acceptance by the market of the Company's product
candidates, if approved; the Company's anticipated capital
requirements, including the amount of capital required for the
continued commercialization of Sunosi and for the Company's
commercial launch of its product candidates, and the potential
impact on the Company's anticipated cash runway; unforeseen
circumstances or other disruptions to normal business operations
arising from or related to COVID-19; and other factors, including
general economic conditions and regulatory developments, not within
the Company's control. The factors discussed herein could cause
actual results and developments to be materially different from
those expressed in or implied by such statements. The
forward-looking statements are made only as of the date of this
press release and the Company undertakes no obligation to publicly
update such forward-looking statements to reflect subsequent events
or circumstance.
Axsome Contact:
Mark Jacobson
Chief Operating Officer
Axsome Therapeutics, Inc.
22 Cortlandt Street, 16th
Floor
New York, NY 10007
Tel: 212-332-3243
Email: mjacobson@axsome.com
www.axsome.com
References
1. American Psychiatric Association.
About The American Journal of Psychiatry. Psychiatry Online.
2022. https://ajp.psychiatryonline.org/about
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SOURCE Axsome Therapeutics Inc