COAST-1 is a Phase 3 trial of AXS-02 in knee
osteoarthritis associated with bone marrow lesions
Axsome Therapeutics, Inc. (NASDAQ:AXSM), a clinical-stage
biopharmaceutical company developing novel therapies for the
management of central nervous system (CNS) disorders, today
announced that an independent data monitoring committee (IDMC) has
conducted an interim analysis of the CREATE-1 trial of AXS-02 in
complex regional pain syndrome (CRPS), and of the COAST-1 trial of
AXS-02 in knee osteoarthritis (OA) associated with bone marrow
lesions (BMLs). The IDMC has recommended that the COAST-1 trial be
continued to full enrollment, and that the CREATE-1 trial be
stopped for futility. In the CREATE-1 trial, AXS-02 treatment
resulted in a significant reduction of serum CTx, a marker of bone
resorption, as compared to placebo (p<0.0001). Further analysis
of the data from the CREATE-1 trial will continue in order to
better understand the basis for the outcome of that trial and to
inform the ongoing clinical development of AXS-02. The IDMC also
reviewed the available safety information in both studies and
confirmed that AXS-02 was safe and generally well-tolerated. AXS-02
is a potent osteoclast inhibitor being developed as an oral,
targeted, non-opioid, potentially first-in-class therapeutic for
chronic pain.
“We are encouraged by the IDMC’s recommendation
for continuation of the COAST-1 trial, by the favorable overall
clinical safety profile of AXS-02, and by the confirmation of
pharmacologic activity of orally administered AXS-02 as
demonstrated by its effects on serum CTx in the CREATE-1 trial,”
said Cedric O’Gorman, M.D., Senior Vice President of Clinical
Development and Medical Affairs of Axsome. “Knee osteoarthritis
associated with bone marrow lesions is a serious and potentially
disabling condition with limited treatment options. The
demonstrated pharmacologic activity of AXS-02 on bone resorption is
relevant not only to knee osteoarthritis but to other potential
indications for AXS-02.”
“The outcome of the CREATE-1 interim analysis is
disappointing, especially in light of its implication for patients
living with complex regional pain syndrome,” said Dr. Herriot
Tabuteau, M.D., Chief Executive Officer of Axsome. “We would like
to thank the patients and the investigators who participated in the
CREATE-1 trial for joining us in our efforts to address this
difficult-to-treat condition. We look forward to assessing next
steps in the COAST-1 trial and to continuing to advance our broad,
late-stage pipeline which includes three other product candidates,
being developed across six different indications, in several either
ongoing or soon to be initiated registration trials.”
In addition to AXS-02, Axsome’s pipeline
includes AXS-05, AXS-07, and AXS-06. AXS-05 is a combination of
dextromethorphan (an NMDA receptor antagonist, sigma-1 receptor
agonist, and serotonin and norepinephrine reuptake inhibitor) and
bupropion (a norepinephrine and dopamine reuptake inhibitor, which
also increases the bioavailability of dextromethorphan). It is in a
Phase 3 trial for treatment resistant depression, a Phase 2/3 trial
for agitation associated with Alzheimer’s disease, with a Phase 2
trial in smoking cessation anticipated to be initiated this
quarter. AXS-07 is an oral, rapidly absorbed, fixed-dose
combination of MoSEIC™ meloxicam and rizatriptan being developed
for the acute treatment of migraine, with a Phase 3 trial in this
indication anticipated to start this year. AXS-06 is a Phase
3-ready, oral, rapidly absorbed, non-opioid, fixed-dose combination
of MoSEIC™ meloxicam and esomeprazole which is being developed for
the treatment of osteoarthritis and rheumatoid arthritis and for
the reduction of the risk of NSAID-associated gastric ulcers.
The COAST-1 trial is a randomized, double-blind,
placebo-controlled, Phase 3 trial in patients with knee OA
associated with BMLs. Subjects in the COAST-1 trial are randomized
in a 1:1 ratio to receive either AXS-02 or placebo once a week for
six weeks. The primary endpoint of the trial is the change in
weekly average daily pain intensity, using the 0-10 numerical
rating scale, at 24 weeks. The COAST-1 interim analysis included 77
subjects and was conducted to assess the assumptions used to
determine the sample size of the study, as well as safety. This
study is being conducted pursuant to a U.S. Food and Drug
Administration (FDA) Special Protocol Assessment. AXS-02 has
received Fast Track designation from the FDA for the treatment of
the pain of knee OA associated with BMLs. The company will assess
next steps for this program.
The CREATE-1 trial was a randomized,
double-blind, placebo-controlled Phase 3 trial in patients with
CRPS. Subjects in the CREATE-1 trial were randomized in a 1:1 ratio
to receive either AXS-02 or placebo once a week for six weeks. The
primary endpoint of the trial was the change in weekly average
daily pain intensity, using the 0-10 numerical rating scale, at 12
weeks. Secondary outcome measures include assessments of the change
in the Patients’ Global Impression of Change, Clinicians’ Global
Impression of Change, and bone turnover measured using serum
carboxy terminal telopeptide of collagen type I (CTx) and serum
procollagen type I N terminal propeptide. The CREATE-1 interim
analysis included 81 subjects and was conducted to assess efficacy
and safety. AXS-02 has received Fast Track designation from the
U.S. Food and Drug Administration (FDA), and orphan drug
designation from the FDA and European Medicines Agency (EMA) for
the treatment of CRPS.
Conference Call Information
Axsome will host a conference call and webcast
today at 8:00 AM Eastern to discuss the results of the interim
analyses as well as to provide a corporate update. To participate
in the live conference call, please dial (844) 698-4029 (toll-free
domestic) or (647) 253-8660 (international), and use the passcode
2093356. The live webcast can be accessed on the "Webcasts &
Presentations" page of the "Investors" section of the Company's
website at axsome.com. A replay of the webcast will be available
for approximately 30 days following the live event.
About Knee Osteoarthritis (OA)
associated with Bone Marrow Lesions (BMLs)
Knee OA is a disorder characterized by
periarticular bone changes, progressive loss of articular
cartilage, joint space narrowing, and eventual total joint failure.
It is clinically manifested by knee pain, significant physical
disability, and reduced quality of life. BMLs are regions of
increased signal intensity on magnetic resonance imaging (MRI) of
the knee in patients with knee OA. BMLs are strongly associated
with the presence and severity of knee pain, and predict disease
severity and structural progression in patients with knee OA, based
on published studies. Results of epidemiological studies suggest
that there are approximately 7 million symptomatic patients in the
United States, 50 years of age and older, with radiographic knee OA
and BMLs.
About Complex Regional Pain Syndrome
(CRPS)
CRPS is a debilitating condition characterized
by severe, continuous, burning or throbbing pain in a limb. The
excessive pain is accompanied by changes in skin color, temperature
and/or swelling. It is considered to be one of the most painful
conditions, results in loss of physical function, and can lead to
significant and sometimes permanent disability. There is currently
no medication approved for the treatment of CRPS.
About AXS-02
AXS-02 (disodium zoledronate tetrahydrate) is a
potent osteoclast inhibitor being developed as an oral, targeted,
non-opioid, potentially first-in-class therapeutic for chronic
pain. AXS-02 is dosed once per week for 6 weeks and thereafter may
have a duration of effect measured in months. AXS-02 has a high
affinity for bone mineral, and reduces osteoclast activity by
inhibiting the farnesyl pyrophosphate synthase (FPPS) enzyme.
AXS-02 is an investigational product candidate not approved by the
FDA. The safety and efficacy of AXS-02 have not yet been
established.
About Axsome Therapeutics,
Inc.
Axsome Therapeutics, Inc. is a clinical-stage
biopharmaceutical company developing novel therapies for the
management of central nervous system (CNS) disorders for which
there are limited treatment options. Axsome’s product candidate
portfolio includes four clinical-stage candidates, AXS-02, AXS-05,
AXS-06, and AXS-07. AXS-05 is currently in a Phase 3 trial in
treatment resistant depression (TRD) and a Phase 2/3 trial in
agitation in patients with Alzheimer’s disease (AD). AXS-05 is also
being developed for smoking cessation. AXS-02 is currently in a
Phase 3 trial in knee osteoarthritis (OA) associated with bone
marrow lesions (BMLs) with an additional Phase 3 trial planned in
chronic low back pain (CLBP) associated with Modic changes (MCs).
AXS-07 is being developed for the acute treatment of migraine.
AXS-06 is being developed for the treatment of osteoarthritis and
rheumatoid arthritis and for the reduction of the risk of
NSAID-associated gastric ulcers. AXS-02, AXS-05, AXS-06, and AXS-07
are investigational drug products not approved by the FDA. For more
information, please visit the company website at www.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
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 and
completion of the trials, futility analyses and receipt of interim
results, which are not necessarily indicative of the final results
of our ongoing clinical trials; 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
U.S. Food and Drug Administration or other regulatory authority
approval of, or other action with respect to, our product
candidates; 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; 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 Senior Vice
President, Operations Axsome Therapeutics, Inc. 25 Broadway, 9th
Floor New York, NY 10004 Tel: 212-332-3243 Email:
mjacobson@axsome.com www.axsome.com
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