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-12 (reboxetine) met the prespecified primary
endpoint and significantly reduced the number of cataplexy attacks
as compared to placebo in patients with narcolepsy in the CONCERT
Phase 2 trial. AXS-12 also significantly reduced excessive daytime
sleepiness (EDS), and improved cognitive function, sleep quality
and sleep-related symptoms. Narcolepsy is a debilitating,
neurological condition characterized by EDS and cataplexy, a sudden
loss of muscle tone triggered by strong emotions. AXS-12 has been
granted Orphan Drug Designation by the U.S. Food and Drug
Administration (FDA) for the treatment of narcolepsy. CONCERT was a
Phase 2, randomized, double-blind, placebo-controlled, crossover,
multicenter, U.S. trial in which 21 patients with a diagnosis of
narcolepsy with cataplexy were all treated with orally administered
AXS-12 for 2 weeks, and with placebo for 2 weeks, with the
treatment periods separated by 1 week of down-titration and
washout.
AXS-12 met the prespecified primary endpoint by
demonstrating a highly statistically significant reduction from
baseline in the mean weekly number of cataplexy attacks, averaged
for the 2-week treatment period (overall treatment effect), as
compared to placebo (p<0.001). At Week 2, AXS-12 demonstrated a
mean reduction of 14.6 cataplexy attacks per week compared to a
reduction of 2.6 attacks per week for placebo (p=0.002),
representing mean reductions of 48.8% and 8.6% from baseline,
respectively. The proportion of patients achieving a 50% or greater
reduction in the weekly number of cataplexy attacks was 76.2% for
AXS-12, compared to 30.0% for placebo (p=0.003) at Week 2. The
improvement in cataplexy was rapid with AXS-12 demonstrating
significant benefit over placebo as early as Week 1
(p<0.001).
AXS-12 significantly improved EDS symptoms
compared to placebo, as measured by the Epworth Sleepiness Scale
(ESS) and by the frequency of inadvertent naps. The improvement on
the ESS with AXS-12 treatment was twice that observed with placebo,
with reductions from baseline in the ESS score of 6.0 and 3.1,
respectively for AXS-12 and placebo (p=0.003). AXS-12 treatment
resulted in a 31.8% mean reduction from baseline in the average
weekly number of inadvertent naps versus a 5.3% mean reduction for
placebo (p<0.001) at Week 2. The improvement in frequency of
inadvertent naps was rapid with AXS-12 demonstrating significant
benefit over placebo as early as Week 1 (p=0.038).
AXS-12 significantly improved cognitive function
compared to placebo over the 2-week treatment period as measured by
the Ability to Concentrate item of the Narcolepsy Symptom
Assessment Questionnaire (NSAQ), which was assessed daily
(p<0.001). For this assessment, patients rated their ability to
concentrate on a 5-point scale (1=very good to 5=very poor). At the
end of treatment, 42.9% of patients had an ability to concentrate
that was “good” to “very good” with AXS-12 treatment, compared to
25.0% of patients with placebo, and 0% of patients at baseline. The
improvement in the ability to concentrate was rapid with AXS-12
demonstrating significant improvement over placebo as early as Week
1 (p=0.007).
AXS-12 significantly improved sleep quality, as
measured by overall improvement and by number of awakenings at
night, and reduced sleep-related symptoms, as compared to placebo.
AXS-12 treatment resulted in 45.0% of patients reporting improved
sleep quality versus 5.3% of patients with placebo (p=0.007).
AXS-12 treatment resulted in 30.0% of patients reporting a
reduction in the number of awakenings at night versus 5.3% of
patients with placebo (p=0.044). AXS-12 treatment also resulted in
greater proportions of patients with reductions in sleep paralysis
episodes, and in hypnagogic hallucinations, as compared to placebo
(p=ns).
“Narcolepsy is a neurological disorder that
interferes with mental and social functioning, increases work and
driving related accidents, and results in a nearly two-fold higher
mortality rate,” said Dr. Michael J. Thorpy, Professor of Neurology
at Albert Einstein College of Medicine. “Medications that have the
potential to reduce cataplexy symptoms, promote wakefulness, and
enhance cognitive function, such as AXS-12, if borne out in Phase 3
trials, could provide new treatment options for patients living
with this debilitating disorder.”
AXS-12 was safe and well tolerated. There were
no serious adverse events reported in the trial, and no
discontinuations due to adverse events. The overall percentage of
patients experiencing adverse events was 42.9% with AXS-12 and
40.0% with placebo, with the most commonly reported adverse events
with AXS-12 treatment being anxiety, constipation, and insomnia.
The completion rate was 91% for patients randomized to treatment
sequence 1 (AXS-12 followed by placebo) and 100% for those
randomized to sequence 2 (placebo followed by AXS-12).
“We are very pleased with the results of the
CONCERT trial, which demonstrated a strong effect of AXS-12 on both
cataplexy and excessive daytime sleepiness symptoms, as well as on
cognitive function, in narcolepsy patients. The improvement in the
ability to concentrate with AXS-12 is especially relevant because
the cognitive impairment associated with narcolepsy is one of the
most distressing aspects of the disease for patients, as
highlighted in the FDA’s The Voice of the Patient report on
Narcolepsy,” said Herriot Tabuteau, MD, Chief Executive Officer of
Axsome. “Based on these positive results, Axsome intends to
initiate Phase 3 trials of AXS-12 in 2020 with the goal of bringing
this differentiated experimental medicine to narcolepsy patients as
soon as possible.”
“The CONCERT trial exemplifies Axsome’s
commitment to accelerating the innovation of effective treatments
for difficult-to-treat CNS disorders such as narcolepsy. Our
approach uses innovative clinical trial designs to effectively
assess the potential of our product candidates to address unmet
medical needs,” said Cedric O’Gorman, MD, Senior Vice President of
Clinical Development and Medical Affairs of Axsome. “Existing
treatment options for narcolepsy are few, do not address all key
symptoms, may not be well tolerated, and are mostly controlled
substances. If successfully developed, AXS-12 may overcome these
limitations and could make it a candidate as foundational therapy
to meaningfully improve the lives of the many narcolepsy
patients.”
Axsome plans to present the detailed results of
the CONCERT trial at upcoming scientific meetings.
Summary of Topline Results of the
CONCERT Trial
Effect on Cataplexy
- AXS-12 was associated with a statistically significant
reduction from baseline in the mean weekly number of cataplexy
attacks, averaged for the 2-week treatment period, as compared to
placebo (p<0.001).
- At Week 2, AXS-12 was associated with a statistically
significant mean reduction from baseline in the weekly number of
cataplexy attacks of 14.6 attacks per week for AXS-12 compared to a
reduction of 2.6 attacks for placebo (p=0.002), representing mean
reductions from baseline of 48.8% and 8.6%, respectively.
- The proportion of patients achieving a 50% or greater reduction
in the weekly number of cataplexy attacks was 76.2% for AXS-12,
compared to 30.0% for placebo (p=0.003) at Week 2.
- The effect of AXS-12 on cataplexy was rapid with AXS-12
demonstrating a statistically significant improvement in the
frequency of cataplexy as compared to placebo as early as Week 1
(p<0.001).
Effect on Excessive Daytime Sleepiness (EDS)
- AXS-12 was associated with a statistically significant mean
reduction in Epworth Sleepiness Scale (ESS) score from baseline as
compared to placebo, with mean reductions of 6.0 and 3.1 points,
respectively for AXS-12 and placebo (p=0.003).
- AXS-12 was associated with a statistically significant
reduction from baseline in the weekly number of inadvertent naps as
compared to placebo, with a mean reduction of 31.8% for AXS-12
versus 5.3% for placebo (p<0.001), at Week 2.
- The improvements in EDS symptoms were rapid with AXS-12
demonstrating significantly greater reductions than placebo in the
number of inadvertent naps at Week 1 (p=0.038).
Effect on Cognitive Function
- AXS-12 significantly improved cognitive function compared to
placebo over the 2-week treatment period as measured by the Ability
to Concentrate item of the Narcolepsy Symptom Assessment
Questionnaire (NSAQ), which was assessed daily (p<0.001).
- At the end of treatment, 42.9% of patients had an ability to
concentrate that was “very good” or “good” with AXS-12 treatment,
compared to 25.0% of patients with placebo, and 0% of patients at
baseline.
- The improvement in the ability to concentrate was rapid with
AXS-12 demonstrating significant improvement over placebo at Week 1
(p=0.007).
Effect on Sleep Quality and Sleep-related
Symptoms
- AXS-12 treatment resulted in 45.0% of patients reporting
improved sleep quality versus 5.3% of patients with placebo
(p=0.007).
- AXS-12 treatment resulted in 30.0% of patients reporting a
reduction in the number of awakenings at night versus 5% of
patients with placebo (p=0.044).
- AXS-12 treatment also resulted in greater proportions of
patients with reductions in sleep paralysis episodes (55.0% vs.
26.3%), and in hypnagogic hallucinations (40.0% vs. 26.3%), as
compared to placebo (p=ns).
Safety and Tolerability
- AXS-12 was safe and well tolerated. There were no serious
adverse events, and no discontinuations due to adverse events.
- The overall rate of adverse events was 42.9% for patients
treated with AXS-12 and 40.0% for patients treated with placebo,
with the most commonly reported adverse events with AXS-12
treatment being anxiety, constipation, and insomnia.
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 CONCERT trial of AXS-12 in narcolepsy. To participate in the
live conference call, please dial (844) 698-4029 (toll-free
domestic) or (647) 253-8660 (international), and use the passcode
6872588. 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 CONCERT Trial
CONCERT (Clinical Outcomes in Narcolepsy and
Cataplexy: An Evaluation of Reboxetine Treatment) was a Phase 2,
double-blind, randomized, placebo-controlled, crossover,
multicenter trial of AXS-12 in patients with narcolepsy. A total of
21 patients with a diagnosis of narcolepsy with cataplexy were
treated for 2 weeks with AXS-12 or with placebo, followed by a
crossover to the other treatment after a 1-week down-titration and
washout period. AXS-12 was administered orally twice daily, with a
total daily dose of 8 mg for Week 1 which was escalated to 10 mg
for Week 2. Patients were randomized in a 1:1 ratio either to
treatment with AXS-12 followed by placebo (sequence 1), or to
treatment with placebo followed by AXS-12 (sequence 2). The average
number of cataplexy attacks at baseline was 30. Key assessments
were made daily using an electronic diary. The prespecified primary
endpoint was the change in the weekly number of cataplexy attacks,
averaged over the 2-week treatment period (overall treatment
effect). Secondary endpoints included changes in the number of
inadvertent naps, cognition, and Epworth Sleepiness Scale.
Cognition was assessed using the Ability to Concentrate item of the
Narcolepsy Symptom Assessment Questionnaire, a patient reported
outcome measure. This item is rated on 5-point scale (1=very good
to 5=very poor). All analyses were conducted on an intent-to-treat
basis.
About Narcolepsy
Narcolepsy is a serious and debilitating
neurological condition that causes dysregulation of the sleep-wake
cycle and is characterized clinically by excessive daytime
sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis,
and disrupted nocturnal sleep. Narcolepsy afflicts an estimated
185,000 individuals in the U.S. Cataplexy is seen in an estimated
70% of narcolepsy patients and is a sudden reduction or loss of
muscle tone while a patient is awake, typically triggered by strong
emotions such as laughter, fear, anger, stress, or excitement.
Narcolepsy interferes with cognitive, psychological, and social
functioning, increases the risk of work- and driving-related
accidents, and is associated with a 1.5 fold higher mortality rate.
Depression is reported in up to 57% of patients.
About AXS-12
AXS-12 (reboxetine) is a highly selective and
potent norepinephrine reuptake inhibitor for the treatment of
narcolepsy. AXS-12 modulates noradrenergic activity to promote
wakefulness, maintain muscle tone and enhance cognition. AXS-12 is
an investigational drug product 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 four clinical-stage candidates,
AXS-05, AXS-07, AXS-09, and AXS-12. AXS-05 is currently in a Phase
3 trial in treatment resistant depression (TRD), a Phase 3 trial in
major depressive disorder (MDD), and a Phase 2/3 trial in agitation
associated with Alzheimer’s disease (AD). AXS-05 is also being
developed for smoking cessation treatment. AXS-07 is currently in
two Phase 3 trials for the acute treatment of migraine. AXS-12 is
currently in a Phase 2 trial in narcolepsy. AXS-05, AXS-07, AXS-09,
and AXS-12 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.
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 ASCEND clinical trial 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 and
the Company’s current expectations regarding its plans for future
equity financings prior to the readout from its Phase 3 trials; 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 Senior Vice
President, Operations 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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