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 AXS-07 substantially and significantly eliminated
migraine pain, and substantially and significantly prevented
progression of migraine pain intensity in the INTERCEPT Phase 3
trial of AXS-07 in the early treatment of migraine. In the trial,
AXS-07 met the co-primary endpoints of freedom from migraine pain
and freedom from most bothersome symptoms as compared to placebo.
AXS-07 is Axsome’s novel, oral, multi-mechanistic investigational
medicine for the acute treatment of migraine. INTERCEPT was a
randomized, double-blind, placebo-controlled trial in which a total
of 302 patients were randomized in a 1:1 ratio to treat a single
migraine attack with a single dose of AXS-07 (20 mg MoSEIC™
meloxicam/10 mg rizatriptan), or placebo, at the earliest sign of
migraine pain, while the pain intensity was mild.
AXS-07 met both of the two co-primary endpoints
by demonstrating a statistically significantly greater percentage
of patients as compared to placebo achieving pain freedom (32.6%
versus 16.3%, p=0.002) and freedom from most bothersome symptom
(43.9% versus 26.7%, p=0.003), 2 hours after dosing. AXS-07 durably
relieved migraine pain with a statistically significantly greater
percentage of patients as compared to placebo achieving sustained
pain freedom from 2 to 24 hours after dosing (22.7% versus 12.6%,
p=0.030), and from 2 to 48 hours after dosing (20.5% versus 9.6%,
p=0.013). AXS-07 rapidly eliminated migraine symptoms, with
numerical separation from placebo as early as 30 minutes for
migraine pain freedom and most bothersome symptom freedom,
achieving statistical significance for migraine pain at 90 minutes
(p=0.003) and at every timepoint thereafter.
A single dose of AXS-07 significantly prevented
progression of migraine pain beyond mild intensity while
significantly reducing the use of rescue medication. Freedom from
pain progression from 2 to 24 hours after dosing was achieved by
73.5% of AXS-07 patients versus 47.4% of placebo patients
(p<0.001). The effect on pain progression translated to a
significant reduction in the use of rescue medication, with only
15.3% of AXS-07 patients requiring rescue medication through 24
hours after dosing, versus 42.2% of placebo patients
(p<0.001).
AXS-07 substantially and significantly reduced
functional disability, and demonstrated overall disease
improvement. AXS-07 treatment resulted in 73.5% of patients able to
perform normal activities at 24 hours compared to 47.4% of placebo
patients (p<0.001). On the Patient Global Impression of Change
(PGI-C) scale, 52.4% of AXS-07 patients were very much or much
improved compared to 27.7% of placebo patients (p<0.001).
“The INTERCEPT study demonstrated high rates of
freedom from migraine pain with AXS-07 treatment, and utilized an
innovative design to evaluate migraine pain progression. It is
remarkable that early treatment with AXS-07 prevented migraine pain
progression in the vast majority of patients and enabled a
similarly high percentage of patients to return to normal
functioning,” said Dr. Stewart Tepper, Professor of Neurology at
the Geisel School of Medicine at Dartmouth. “The multiple
mechanisms of AXS-07 address the many disordered physiological
processes implicated in migraine attacks. These results, coupled
with previous clinical data showing superiority of AXS-07 over an
active comparator, provide clinical evidence that this synergistic,
multi-mechanistic approach and the rapid absorption of AXS-07 may
translate to important benefits for a wide range of patients. As
clinicians continue to seek options for their patients with
improved efficacy over currently available therapies, AXS-07 may
offer an important new treatment for this disabling
condition.”
AXS-07 was generally safe and well tolerated in
the trial. The most commonly reported adverse events with AXS-07
were somnolence, dizziness, and paresthesia, all of which occurred
at a rate of less than five percent. There were no serious adverse
events in the trial.
“We are very pleased with the strong results of
the Phase 3 INTERCEPT trial, which confirm the superior and durable
efficacy of AXS-07. The prevention of migraine pain progression,
and the substantial increase in the rate of pain freedom
demonstrated with early treatment with AXS-07, expand and enhance
its differentiated profile for the acute treatment of migraine,”
said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “With
INTERCEPT and the previously completed MOMENTUM Phase 3 trial in
patients with a history of inadequate response to prior acute
treatments, AXS-07 has now been evaluated in two positive
well-controlled trials. These trials demonstrate the efficacy of
AXS-07 against potent active and placebo comparators, across a
spectrum of migraine attack settings, regardless of the timing of
migraine treatment, disease severity, or baseline pain intensity.
INTERCEPT strengthens our planned NDA for AXS-07 in the acute
treatment of migraine, which remains on track to be submitted to
the FDA in the fourth quarter.”
AXS-07 has been evaluated in the completed
MOMENTUM Phase 3 trial for which positive results were previously
announced. The MOMENTUM trial enrolled only patients with a history
of inadequate response to prior acute treatments, with patients
waiting to treat their attacks only when the migraine pain had
reached moderate or severe intensity. This is in contrast to the
INTERCEPT trial, which enrolled all comers and in which patients
were instructed to administer AXS-07 at the earliest sign of
migraine pain while the pain was mild, before progressing to
moderate or severe intensity.
“Migraine is one of the most disabling
disorders, incapacitating sufferers and seriously damaging home
life, social activity and the ability to work. Published surveys
have underscored that patients remain dissatisfied with the
efficacy of currently available therapies,” said Cedric O’Gorman,
MD, Senior Vice President of Clinical Development and Medical
Affairs of Axsome. “The results of the INTERCEPT trial demonstrate
for the first time that AXS-07 can halt migraine pain progression
before reaching moderate or severe intensity. These data grow the
body of clinical evidence in support of the potential of AXS-07 to
be a multi-mechanistic treatment for migraine with efficacy that is
superior to the current standard of care, and which can rapidly,
robustly, and durably alleviate symptoms, and return patients to
their normal daily activities.”
AXS-07 is a novel, oral, rapidly absorbed,
multi-mechanistic investigational medicine for the acute treatment
of migraine, consisting of MoSEIC™ meloxicam and rizatriptan.
AXS-07 is thought to act by inhibiting CGRP release, reversing
CGRP-mediated vasodilation, and inhibiting neuro-inflammation, pain
signal transmission, and central sensitization. Axsome’s MoSEIC™
technology significantly increases the speed of absorption of the
meloxicam component after oral administration while maintaining a
long plasma half-life. AXS-07 is covered by more than 30 issued
U.S. and international patents providing protection out to 2036,
and Axsome maintains worldwide rights.
Detailed study results, including additional
secondary endpoints, will be submitted for presentation at upcoming
medical meetings and for publication.
Summary of Topline Results of the
INTERCEPT Trial
Patient Population
- Patients were instructed to
administer AXS-07 at the earliest sign of migraine pain, while the
pain was mild, before progressing to moderate or severe
intensity.
- Enrolled all comers.
Co-Primary Endpoints, Onset, and Durability
- AXS-07 demonstrated statistically
significant improvement as compared to placebo on both of the
co-primary endpoints of pain freedom (32.6% versus 16.3%, p=0.002),
and freedom from most bothersome symptom (43.9% versus 26.7%,
p=0.003), 2 hours after dosing.
- AXS-07 was numerically superior to
placebo as early as 30 minutes for migraine pain freedom and most
bothersome symptom freedom, achieving statistical significance for
migraine pain freedom at 90 minutes (p=0.003) and at every time
thereafter.
- Sustained pain freedom from 2 to 24
hours after dosing was experienced by 22.7% of patients treated
with AXS-07, compared to 12.6% with placebo (p=0.030).
- Sustained pain freedom from 2 to 48
hours after dosing was experienced by 20.5% of patients treated
with AXS-07, compared to 9.6% with placebo (p=0.013).
Prevention of Migraine Pain Progression, and
Rescue Medication Use
- AXS-07 prevented progression of
migraine pain intensity beyond mild in 73.5% of patients versus
47.4% of placebo patients from 2 to 24 hours (p<0.001).
- Rescue medication was used by 15.3%
of AXS-07 patients, compared to 42.2% of placebo over 24 hours
(p<0.001).
Functional and Global Improvement
- The ability to perform normal
activities was achieved by 73.5% of AXS-07 patients compared to
47.4% of placebo patients at 24 hours (p<0.001).
- On the Patient Global Impression of
Change (PGI-C) scale, 52.4% of AXS-07 patients were very much or
much improved compared to 27.7% of placebo patients
(p<0.001).
Safety and Tolerability
- AXS-07 was generally safe and well
tolerated in the trial.
- The most commonly reported adverse
events with AXS-07 were somnolence, dizziness, and paresthesia, all
of which occurred at a rate of less than five percent.
- There were no serious adverse
events in the trial.
Conference Call Information
Axsome will host a conference call and webcast
with slides today at 8:00 AM Eastern to discuss the topline results
of the INTERCEPT trial of AXS-07 in the early treatment of
migraine. To participate in the live conference call, please dial
(844) 698-4029 (toll-free domestic) or (647) 253-8660
(international), and use the passcode 5960729. 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 the INTERCEPT Trial
INTERCEPT (Initiating Early Control of Migraine
Pain and Associated Symptoms) is a Phase 3, randomized,
double-blind, multicenter, placebo-controlled trial evaluating the
early treatment of migraine with AXS-07. A total of 302 patients
were randomized in a 1:1 ratio to treatment with AXS-07 or placebo.
Patients were instructed to administer AXS-07 at the earliest sign
of migraine pain, while the pain was mild. The two co-primary
endpoints of the trial are the proportion of patients who are free
from headache pain two hours after dosing, and the proportion of
patients who no longer suffer from their most bothersome
migraine-associated symptom (nausea, photophobia, or phonophobia)
two hours after dosing.
About Migraine
Over 37 million Americans suffer from migraine
according to the Centers for Disease Control, and it is the leading
cause of disability among neurological disorders in the United
States according to the American Migraine Foundation. Migraine is
characterized by recurrent attacks of pulsating, often severe and
disabling head pain associated with nausea, and sensitivity to
light and or sound. It is estimated that migraine accounts for $78
billion in direct (e.g. doctor visits, medications) and indirect
(e.g. missed work, lost productivity) costs each year in the United
States [1]. Published surveys of migraine sufferers indicate that
more than 70% are not fully satisfied with their current treatment,
that nearly 80% would try a new therapy, and that they desire
treatments that work faster, more consistently, and result in less
symptom recurrence [2,3].
About AXS-07
AXS-07 is a novel, oral, investigational
medicine with distinct dual mechanisms of action under development
for the acute treatment of migraine. AXS-07 consists of MoSEIC™
meloxicam and rizatriptan. Meloxicam is a new molecular entity for
migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced
Inclusion Complex) technology, which results in rapid absorption of
meloxicam while maintaining a long plasma half-life. Meloxicam is a
COX-2 preferential non-steroidal anti-inflammatory drug and
rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to
provide rapid, enhanced and consistent relief of migraine, with
reduced symptom recurrence. AXS-07 is not approved by
the FDA.
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 core CNS product
candidate portfolio includes five clinical-stage candidates,
AXS-05, AXS-07, AXS-09, AXS-12, and AXS-14. AXS-05 is being
developed for major depressive disorder (MDD), treatment resistant
depression (TRD), Alzheimer’s disease (AD) agitation, and for
smoking cessation treatment. AXS-07 is being developed for the
acute treatment of migraine. AXS-12 is being developed for the
treatment of narcolepsy. AXS-14 is being developed for the
treatment of fibromyalgia. AXS-05, AXS-07, AXS-09, AXS-12, and
AXS-14 are investigational drug products not approved by the FDA.
For more information, please visit the Company’s website at
axsome.com. The Company may occasionally disseminate material,
nonpublic information on the company website.
References
- Gooch CL, Pracht E, Borenstein AR.
The burden of neurological disease in the United States: A summary
report and call to action. Ann Neurol. 2017 Apr;
81(4):479-484.
- Smelt AF, Louter MA, Kies DA, Blom
JW, Terwindt GM, van der Heijden GJ, De Gucht V, Ferrari MD,
Assendelft WJ. What do patients consider to be the most important
outcomes for effectiveness studies on migraine treatment? Results
of a Delphi study. PLoS One. 2014 Jun 16;9(6):e98933.
- Lipton RB, Stewart WF. Acute
migraine therapy: do doctors understand what patients with migraine
want from therapy? Headache. 1999;39(suppl 2):S20-S26.
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, 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 a new drug application (“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 U.S. Food and Drug
Administration (“FDA”) or other regulatory authority approval of,
or other action with respect to, our product candidates (including,
but not limited to, FDA’s agreement with the Company’s plan to
discontinue the bupropion treatment arm of the ADVANCE-1 study in
accordance with the independent data monitoring committee’s
recommendations); the potential for the MOMENTUM clinical trial to
provide a basis for approval of AXS-07 for the acute treatment of
migraine in adults with or without aura, pursuant to our special
protocol assessment; 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 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. The data disclosed in this press release are
considered topline data and subject to further statistical review
and the final results may vary.
Axsome Contact: Mark Jacobson Chief Operating
Officer Axsome Therapeutics, Inc. 200 Broadway, 3rd Floor New York,
NY 10038 Tel: 212-332-3243 Email: mjacobson@axsome.com
www.axsome.com
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