Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical
company developing and delivering novel therapies for the
management of central nervous system (CNS) disorders, today
announced that AXS-12 (reboxetine), a highly selective and potent
norepinephrine reuptake inhibitor and cortical dopamine modulator,
achieved the primary endpoint and significantly reduced the
frequency of cataplexy attacks as compared to placebo in patients
with narcolepsy in the SYMPHONY Phase 3 trial. AXS-12 also reduced
excessive daytime sleepiness (EDS) severity, improved cognitive
function, and reduced overall narcolepsy severity as compared to
placebo. SYMPHONY was a Phase 3 multicenter, randomized,
double-blind, placebo-controlled trial in which 90 patients with a
diagnosis of narcolepsy with cataplexy were randomized to treatment
with AXS-12 or placebo for 5 weeks.
“AXS-12 is a novel therapeutic approach to the
treatment of narcolepsy as evidenced by the strong clinical results
generated from the Phase 3 SYMPHONY trial, including a rapid and
significant reduction in cataplexy events compared to placebo,”
commented Dr. Michael Thorpy, Director of the Sleep-Wake Disorders
Center at the Montefiore Medical Center and Professor of Neurology
at Albert Einstein College of Medicine. “Despite the existence of
multiple approved narcolepsy treatments, significant unmet need
still exists given the high rates of persistent symptoms reported
by patients. Based on the concurrent improvements observed on
cataplexy, severity of excessive daytime sleepiness, cognition and
overall function, I believe AXS-12 represents a meaningful
enhancement to the treatment armamentarium for narcolepsy patients
and clinicians and will be a welcome treatment option in our fight
against the devastating impact of narcolepsy on patients and their
loved ones.”
AXS-12 met the primary endpoint by demonstrating
a substantial and statistically significant reduction from baseline
in weekly cataplexy attacks compared to placebo at Week 5, with
reductions of 83% for AXS-12 and 66% for placebo (p=0.018). AXS-12
rapidly reduced weekly cataplexy attacks, demonstrating at Week 1 a
reduction of 56% compared to a reduction of 31% for placebo
(p=0.007).
AXS-12 induced remission of cataplexy and
increased cataplexy-free days compared to placebo. Remission of
cataplexy, defined as a 100% reduction from baseline, was achieved
at Week 5 by 33% of AXS-12 treated patients compared to 9.5% of
placebo patients (p=0.008). Achievement of remission was rapid,
being experienced at Week 2 by 24% of AXS-12 treated patients
compared to 4.5% of placebo patients (p=0.008). AXS-12 increased
the percentage of cataplexy-free days per week, defined as days
with zero cataplexy attacks, to 84.5% at Week 5 compared to 22.6%
for placebo (p=0.014).
AXS-12 significantly reduced excessive daytime
sleepiness (EDS) severity, assessed by the Clinician Global
Impression of Severity (CGI-S) scale for EDS, compared to placebo
at Week 5 with mean reductions of 1.8 points for AXS-12 compared to
0.9 points for placebo (p=0.027). Rapid improvement on the CGI-S
for EDS was seen as early as Week 1 compared to placebo (p=0.006).
AXS-12 concurrently improved EDS and cataplexy as compared to
placebo. Concurrent EDS and cataplexy response was achieved at Week
5 by 57% of patients treated with AXS-12 compared to 33% of placebo
patients (p=0.029). Concurrent EDS and cataplexy response was
defined as a ≥30% reduction in inadvertent naps (EDS response), and
a ≥50% reduction in cataplexy attacks (cataplexy response).
A decrease in the number of inadvertent naps was
experienced by 54% of AXS-12 patients at Week 5 compared to 28% of
placebo patients (p=0.016), assessed by the Narcolepsy Symptom
Assessment Questionnaire (NSAQ). Improvement on the Epworth
Sleepiness Scale (ESS) was numerically greater for AXS-12 than for
placebo, with mean reductions from baseline of 4.7 points for
AXS-12 compared to 3.4 points for placebo. A ≥3-point improvement
from baseline on the ESS was achieved by 60% of AXS-12 patients who
had a cataplexy response.
AXS-12 significantly improved concentration and
memory as measured by the Cognitive Function Items of the
Functional Outcomes of Sleep Questionnaire (FOSQ-10) at Week 5
(p=0.004). AXS-12 concurrently improved cognition and cataplexy as
compared to placebo. Concurrent cognitive and cataplexy response
was achieved at Week 5 by 41% of patients treated with AXS-12
compared to 17% of placebo patients (p=0.016). Response was defined
by an increase in days patients rated their Ability to Concentrate
as very good or good (cognitive response), and a ≥50% reduction in
cataplexy attacks (cataplexy response).
AXS-12 improved narcolepsy overall disease
condition, and patient function and quality of life. Clinicians
reported a rapid and significant reduction in overall narcolepsy
severity (CGI-S for narcolepsy overall) for patients treated with
AXS-12 compared to placebo at Week 5 (p=0.007), with improvements
observed as early as Week 1 (p<0.001). AXS-12 demonstrated
significant improvement in overall patient function and quality of
life as measured by the FOSQ-10 total score as compared to placebo
at Week 5 (p=0.005).
Anxiety and depression, known common narcolepsy
co-morbidities, was reported by 45% of study participants at
baseline, as assessed by the EuroQol (EQ-5D-5L). Improvement from
baseline in the Anxiety/Depression domain of the EQ-5D-5L was
achieved by 55% of patients treated with AXS-12 compared to 32% of
placebo patients (p=0.146).
“The SYMPHONY Phase 3 trial results confirm the
promise and potential of AXS-12 for the treatment of narcolepsy,”
said Dr. Herriot Tabuteau, CEO of Axsome Therapeutics. “Treatment
with AXS-12 resulted in rapid and substantial reduction of
cataplexy events, the primary endpoint of the SYMPHONY trial, while
evidencing improvement across a range of validated global clinical,
patient-reported, quality of life, and functional outcome measures.
Collectively, the data generated in SYMPHONY highlight AXS-12’s
positive therapeutic impact and are consistent with the results
from the previously completed positive CONCERT trial. As a next
step, we look forward to completing the ongoing open label safety
extension trial of AXS-12 as we work to bring this treatment to
individuals living with narcolepsy.”
AXS-12 was well tolerated in the trial. The most
commonly reported adverse events in the AXS-12 arm were dry mouth
(n=6), nausea (n=6), and constipation (n=4), which were overall
mild to moderate. The rates of discontinuation due to adverse
events was low (n=1 in each of AXS-12 and placebo arms). There were
no serious adverse events in the trial.
AXS-12 was granted Orphan Drug Designation for
the treatment of narcolepsy in October 2018. Orphan Drug
Designation is granted to promising drugs intended for the safe and
effective treatment of rare diseases, defined as those affecting
fewer than 200,000 people in the U.S. This designation may entitle
Axsome to a period of seven years of marketing exclusivity in the
U.S. upon FDA approval and a waiver of the Company’s obligation to
pay the FDA application user fees for the product as required by
the Prescription Drug User Fee Act. AXS-12 is covered by issued
patents providing protection to at least 2039.
Axsome plans to present the detailed results of the SYMPHONY
trial at upcoming scientific meetings.
Summary of Topline Results of the
SYMPHONY Trial
Effect on Cataplexy
- AXS-12
demonstrated a substantial and statistically significant reduction
from baseline in weekly cataplexy attacks compared to placebo at
Week 5, with reductions of 83% for AXS-12 and 66% for placebo
(p=0.018).
- AXS-12
demonstrated a statistically significant reduction from baseline in
weekly cataplexy attacks compared to placebo at Week 1, with
reductions of 56% for AXS-12 and 31% for placebo (p=0.007).
- AXS-12
achieved remission of cataplexy (100% reduction from baseline) at
Week 5 in 33% of patients compared to 9.5% of placebo patients
(p=0.008).
-
Remission at Week 2 was achieved by 24% of AXS-12 treated patients
compared to 4.5% of placebo patients (p=0.008).
- AXS-12
increased the percentage of cataplexy free days (days with zero
cataplexy attacks) to 84% at Week 5 compared to 22% for placebo
(p=0.014).
Effect on Excessive Daytime Sleepiness (EDS)
- AXS-12
significantly reduced EDS severity compared to placebo at Week 5
with mean reductions on the CGI-S for EDS of 1.8 points for AXS-12
compared to 0.9 points for placebo (p=0.027).
- Improvement on
the CGI-S for EDS was seen as early as Week 1 compared to placebo
(p=0.006).
- Concurrent EDS
and cataplexy response was achieved at Week 5 by 57% of patients
treated with AXS-12 compared to 33% of placebo patients
(p=0.029).
- A
reduction in the number of inadvertent naps was experienced by 54%
of AXS-12 patients at Week 5 compared to 28% of placebo patients
(p=0.016), assessed by the NSAQ.
- Mean
reductions from baseline on the ESS were 4.8 points for AXS-12 and
3.4 points for placebo. A ≥3-point improvement from baseline on the
ESS was achieved by 60% of AXS-12 patients who had a cataplexy
response.
Effect on Cognitive Function
- AXS-12
significantly improved concentration and memory as measured by the
Cognitive Function Items of the FOSQ-10 at Week 5 (p=0.004).
-
Concurrent cognitive response (increase in days with very good or
good Ability to Concentrate) and cataplexy response was achieved at
Week 5 by 41% of patients treated with AXS-12 compared to 17% of
placebo patients (p=0.016).
Effect on Narcolepsy Overall, Function and
Quality of Life
- AXS-12
treatment resulted in significant reduction in overall narcolepsy
severity (CGI-S for narcolepsy overall) compared to placebo at Week
5 (p=0.007).
-
Improvement in the CGI-S for narcolepsy overall for AXS-12 compared
to placebo was observed as early as Week 1 (p<0.001).
- AXS-12
demonstrated significant improvement in overall patient function
and quality of life as measured by the FOSQ-10 total score as
compared to placebo at Week 5 (p=0.005).
Anxiety/Depression Comorbidity
-
Anxiety and depression was reported by 45% of study participants at
baseline, as assessed by the EQ-5D-5L.
-
Improvement from baseline in the Anxiety/Depression domain of the
EQ-5D-5L was achieved by 55% of patients treated with AXS-12
compared to 32% of placebo patients (p=0.146).
Safety and Tolerability
- AXS-12
was well tolerated in the trial.
- The
most commonly reported adverse events in the AXS-12 arm were dry
mouth (n=6), nausea (n=6), and constipation (n=4), which were
overall mild to moderate.
Conference Call Information
Axsome will host a conference call and webcast
today at 8:00 AM Eastern to discuss the topline SYMPHONY
study results in narcolepsy. To participate in the live conference
call, please dial (877) 405-1239 (toll-free domestic). 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 SYMPHONY Trial
SYMPHONY (Study Evaluating a Mechanistic
Approach to Treating Narcolepsy) was a Phase 3, randomized,
double-blind, multicenter, placebo-controlled trial to assess the
efficacy and safety of AXS-12 in patients with narcolepsy. In all,
a total of 90 patients were randomized in a 1:1 ratio to treatment
with AXS-12 or placebo for 5 weeks. Participants took either AXS-12
(5 mg) or placebo once daily during Week 1 followed by twice daily
dosing during Weeks 2-5. The median number of cataplexy attacks at
baseline was 20 and Epworth Sleep Scores were 17.8 at baseline. The
prespecified primary endpoint was the change in frequency of weekly
cataplexy attacks. Other symptoms of narcolepsy as well as safety
and tolerability were assessed throughout the study.
About Narcolepsy
Narcolepsy is a serious and debilitating orphan
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. 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.
About AXS-12
AXS-12 (reboxetine) is a highly selective and
potent norepinephrine reuptake inhibitor and cortical dopamine
modulator under development for the treatment of narcolepsy. AXS-12
is thought to modulate noradrenergic activity to promote maintain
tone during wakefulness, and noradrenergic and cortical dopamine
signaling to promote wakefulness and enhance cognition. AXS-12 has
been granted U.S. Food and Drug Administration (FDA) Orphan Drug
Designation for the treatment of narcolepsy. AXS-12 is covered by
issued patents providing protection to at least 2039. AXS-12 is an
investigational drug product not approved by the FDA.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical
company developing and delivering novel therapies for central
nervous system (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 Sunosi® and Auvelity® products
and the success of our efforts to obtain any additional
indication(s) with respect to solriamfetol and/or AXS-05; 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 revenues or expenses), futility
analyses and receipt of interim results, which are not necessarily
indicative of the final results of our ongoing clinical trials,
and/or data readouts, 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 statements
regarding the timing of any NDA submission; 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 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 products and product
candidates, if approved; the Company’s anticipated capital
requirements, including the amount of capital required for the
continued commercialization of Sunosi and Auvelity and for the
Company’s commercial launch of its other product candidates, if
approved, 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 geo-political
conflicts or a global pandemic 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 Contacts:
Investors:Mark JacobsonChief Operating OfficerAxsome
Therapeutics, Inc.One World Trade Center, 22nd FloorNew York, NY
10007Tel: 212-332-3243Email: mjacobson@axsome.com
www.axsome.com
Media:Darren OplandDirector, Corporate CommunicationsAxsome
Therapeutics, Inc.One World Trade Center, 22nd FloorNew York, NY
10007Tel: 929-837-1065Email: dopland@axsome.com www.axsome.com
Axsome Therapeutics (NASDAQ:AXSM)
Historical Stock Chart
From Mar 2024 to Apr 2024
Axsome Therapeutics (NASDAQ:AXSM)
Historical Stock Chart
From Apr 2023 to Apr 2024