Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical
company developing and delivering novel therapies for the
management of central nervous system (CNS) disorders, announced
that Sunosi met the primary endpoint in the SHARP study and
significantly improved cognitive function, measured using the Digit
Symbol Substitution Test subtest of the Repeatable Battery for the
Assessment of Neuropsychological Status (DSST RBANS), as compared
to placebo in cognitively impaired patients with excessive daytime
sleepiness (EDS) associated with obstructive sleep apnea (OSA).
Superiority of Sunosi as compared to placebo was further
demonstrated using patient-reported measures of cognitive function.
In the study, Sunosi replicated previous findings by significantly
reducing EDS symptoms as compared to placebo.
SHARP (Solriamfetol's Effect on Cognitive Health
in Apnea Participants During a Randomized Placebo-controlled Study)
was a randomized, double-blind, placebo-controlled, crossover,
multicenter, trial in 59 patients with EDS associated with OSA, and
impaired cognitive function. Patients were all treated with Sunosi
for 2 weeks, and with placebo for 2 weeks, with the treatment
periods separated by 1 week of down-titration and washout.
On the study’s primary endpoint, Sunosi
demonstrated statistically significant improvement in cognitive
function compared to placebo as assessed by the change from
baseline on the DSST RBANS (6.49 vs. 4.75, p=0.009), with an effect
size of 0.36. The DSST RBANS is an objective neuropsychological
test that assesses executive function, processing speed and
attention. Statistically significant improvement in cognitive
function with Sunosi treatment was also demonstrated using the
British Columbia Cognitive Complaints Inventory (BC-CCI) overall
score compared to placebo (p=0.002), with an effect size of 0.43.
The BC-CCI is a patient-reported test that assesses domains of
memory, concentration, trouble expressing thoughts, word finding,
and problem solving.
Sunosi significantly improved EDS symptoms
compared to placebo, as measured by the Epworth Sleepiness Scale
(ESS). The improvement on the ESS with Sunosi treatment was
approximately twice that observed with placebo (p=0.004), with an
effect size of 0.50.
The most commonly reported adverse events with
Sunosi treatment (incidence ≥3%) were nausea (6.9%) and anxiety
(3.4%). The study completion rate was 96.7% for patients randomized
to each treatment sequence (Sunosi followed by placebo, or placebo
followed by Sunosi).
“Cognitive impairment in patients with EDS
associated with OSA is extremely common and one of the most
burdensome symptoms for patients,” said Richard Bogan, MD, FCCP,
Associate Clinical Professor at the University of South Carolina
School of Medicine, Associate Clinical Professor at Medical
University of South Carolina, and Principal of Bogan Sleep
Consultants. “The results of the SHARP study demonstrate a
clinically important improvement in cognitive function with Sunosi
treatment in cognitively impaired patients with EDS and OSA. Of
importance, the results from the patient-reported outcomes are
consistent with the objective measures, meaning that patients
themselves were able to perceive improvements in their cognitive
performance with Sunosi treatment. The ability to address cognitive
symptoms would represent an important advancement in the treatment
of EDS associated with OSA.”
"We are excited by the demonstrated effect of
Sunosi on cognition, using both objective and patient-reported
outcomes in the SHARP trial in patients with EDS and OSA
experiencing cognitive impairment at baseline," said Herriot
Tabuteau, MD, Chief Executive Officer of Axsome. "We plan to
discuss these results with the FDA as soon as possible. In
addition, we recently presented new data demonstrating that
solriamfetol has activity at TAAR1, a previously unrecognized
target for this molecule which further supports its exploration in
cognition."
Detailed study results will be submitted for
presentation at upcoming medical meetings and for publication.
New Data Demonstrating Activation of
TAAR1 by Solriamfetol Presented at 2022 Psych Congress
New preclinical pharmacology studies have
identified agonist activity at the trace amine-associated receptor
1 (TAAR1) and lower potency agonist activity at 5-HT1A receptors
for solriamfetol, in addition to its activity as a dopamine and
norepinephrine reuptake inhibitor (DNRI). TAAR1 is a G-protein
coupled receptor with affinity for the trace amines, and TAAR1
agonists have demonstrated pro-cognitive and wake-promoting effects
in rodents and primates [1,2].
Results of the studies demonstrated that
solriamfetol activates human TAAR1 in vitro at potencies that are
within the clinically relevant plasma concentration range and
overlap with observed dopamine and norepinephrine transporter
inhibitory potencies [3]. No human TAAR1 activity was observed for
the wake promoting agent (WPA) modafinil or the DNRI bupropion. In
addition, similar to known TAAR1 agonists, solriamfetol reduced the
firing frequency of mouse VTA dopamine neurons in a D2-sensitive
manner.
These findings were recently presented at the
2022 Psych Congress on September 18, 2022.
The mechanism of action of solriamfetol to
improve wakefulness in patients with excessive daytime sleepiness
associated with narcolepsy or obstructive sleep apnea, and to
potentially affect cognition, is unclear.
About the SHARP Trial
SHARP (Solriamfetol’s Effect on Cognitive Health
in Apnea Participants During a Randomized Placebo-controlled Study)
was a randomized, double-blind, placebo-controlled, crossover,
multicenter, trial in which 59 patients with EDS and OSA, who were
experiencing cognitive impairment, were all treated with Sunosi
(solriamfetol) for 2 weeks, and with placebo for 2 weeks, with the
treatment periods separated by 1 week of down-titration and
washout. Patients were randomized in a 1:1 ratio either to
treatment with Sunosi followed by placebo (sequence 1), or to
treatment with placebo followed by Sunosi (sequence 2). Sunosi was
administered orally once daily, starting at 75 mg per day for the
first three days and 150 mg per day for the remainder of the 2-week
treatment period. The primary outcome measure was the Digit Symbol
Substitution Test subtest of the Repeatable Battery for the
Assessment of Neuropsychological Status (DSST RBANS). The Digit
Symbol Substitution subtest is also referred to as “Coding.” The
prespecified primary endpoint was the change from baseline in
cognitive function as measured by the DSST RBANS after 2 weeks of
treatment (average of the 2-, 4-, 6-, and 8-hour post-dose DSST
RBANS scores). Secondary endpoints included patient reported
measures of cognition including the British Columbia Cognitive
Complaints Inventory (BC-CCI) and the Patient Global Impression of
Severity (PGI-S) for cognitive symptoms; and the Epworth Sleepiness
Scale (ESS) to measure wakefulness. The secondary endpoints were
analyzed in a pre-specified testing sequence. All analyses were
conducted on an intent-to-treat basis.
About Sunosi®
(solriamfetol)
Sunosi is a dual-acting dopamine and
norepinephrine reuptake inhibitor indicated to improve wakefulness
in adult patients with excessive daytime sleepiness (EDS)
associated with narcolepsy or obstructive sleep apnea (OSA). Sunosi
received U.S. Food and Drug Administration approval on March 20,
2019 to improve wakefulness in adult patients with EDS associated
with narcolepsy or OSA and was designated a Schedule IV medicine by
the U.S. Drug Enforcement Agency on June 17, 2019. SK
Biopharmaceuticals Co., Ltd., the discoverer of the compound,
maintains rights in 12 Asian markets, including Korea, China and
Japan. Sunosi has orphan drug designation for narcolepsy in the
United States. Sunosi is protected by a robust patent estate with
expiries out to 2040. Sunosi is not approved by the FDA for
improving cognitive function in patients with EDS due to OSA.
More information about Sunosi, including
Full Prescribing Information and Medication Guide, is
available here.
Important Safety
Information
SUNOSI (solriamfetol) is available in 75
mg and 150 mg tablets and is a federally controlled substance (CIV)
because it contains solriamfetol that can be a target for people
who abuse prescription medicines or street drugs. Keep
SUNOSI in a safe place to protect it from theft. Never give or sell
your SUNOSI to anyone else because it may cause death or harm them
and it is against the law. Tell your doctor if you have ever abused
or been dependent on alcohol, prescription medicines, or street
drugs.
Before taking SUNOSI, tell your doctor
about all of your medical conditions, including if
you:
- have heart problems, high blood
pressure, kidney problems, diabetes, or high cholesterol.
- have had a heart attack or a
stroke.
- have a history of mental health
problems (including psychosis and bipolar disorders), or of drug or
alcohol abuse or addiction.
- are pregnant or planning to become
pregnant. It is not known if SUNOSI will harm your unborn
baby.
- are
breastfeeding or plan to breastfeed. It is not known if SUNOSI
passes into your breast milk. Talk to your doctor about the best
way to feed your baby if you take SUNOSI.
What are the possible side effects of
SUNOSI?
SUNOSI may cause serious side effects,
including:
- Increased blood pressure and heart rate.
SUNOSI can cause blood pressure and heart rate increases that can
increase the risk of heart attack, stroke, heart failure, and
death. Your doctor should check your blood pressure before, and
during, treatment with SUNOSI. Your doctor may decrease your dose
or tell you to stop taking SUNOSI if you develop high blood
pressure that does not go away during treatment with SUNOSI.
- Mental (psychiatric) symptoms including anxiety,
problems sleeping (insomnia), irritability, and agitation.
Tell your doctor if you develop any of these symptoms. Your doctor
may change your dose or tell you to stop taking SUNOSI if you
develop side effects during treatment with SUNOSI.
The most common side effects of SUNOSI
include:
- headache
- decreased appetite
- problems sleeping
- nausea
- anxiety
These are not all the possible side effects of
SUNOSI. Call your doctor for advice about side effects.
You are encouraged to report negative side
effects of prescription drugs to the FDA. Visit
www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please find full Prescribing Information here:
https://sunosihcp.com/assets/files/sunosi-pi.pdf
SUN CON ISI 05/2022
About Obstructive Sleep Apnea, Excessive
Daytime Sleepiness, and Associated Cognitive
Impairment
Obstructive sleep apnea, commonly referred to as
sleep apnea, is a highly prevalent disease (as high as 14% in men
and 5% in women) in which excessive daytime sleepiness is a major
presenting complaint in many cases. Positive Airway Pressure (PAP)
therapy, with its most common form being Continuous Positive Airway
Pressure (CPAP), has been shown to be an effective therapy for
sleep apnea that frequently results in improvement in excessive
daytime sleepiness in many patients; however, not all patients
tolerate CPAP therapy and among those who tolerate CPAP, usage is
highly variable. Excessive daytime sleepiness may persist in people
with sleep apnea despite using CPAP. Cognitive impairment is a
common and disruptive symptom in patients with EDS associated with
OSA, that may be experienced in the vast majority of patients
[4].
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® product and the success
of our efforts to obtain any additional indication(s) with respect
to Sunosi; the commercial success of our Auvelity™ product and the
success of our efforts to obtain any additional indication(s) with
respect to 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
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,; 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 product candidates,
if approved; the Company’s anticipated capital requirements,
including the amount of capital required for the successful
commercialization of Sunosi and Auvelity and for the Company’s
commercial launch of its other 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 JacobsonChief Operating Officer Axsome
Therapeutics, Inc.22 Cortlandt Street, 16th FloorNew York, NY
10007Tel: 212-332-3243Email: mjacobson@axsome.com
www.axsome.com
References
- Dedic et al.
Int J Mol Sci. 2021 Dec 7;22(24):13185.
- Goonawardena et
al. Neuropsychopharmacology. 2019 Jul;44(8):1485-1493.
- Gursahani et
al. Preclinical Pharmacology of Solriamfetol: Potential Mechanisms
for Wake Promotion. Psych Congress September 2022. New Orleans,
LA.
- Waldman et al.
Health Qual Life Outcomes. 2020 May 7;18(1):128
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