Minerva Neurosciences, Inc. (NASDAQ: NERV), a clinical-stage
biopharmaceutical company focused on the development of therapies
to treat central nervous system (CNS) disorders, today announced
results of a clinical trial (ISM2005) of seltorexant (MIN-202) in
patients with insomnia disorder that demonstrated highly
statistically significant (p ≤0.001) and clinically meaningful
improvement on LPS at Night 1, the primary endpoint of the study.
The mean decrease from baseline at Night 1 in LPS was 15 minutes
for placebo, 30 minutes for seltorexant 5 mg, 50 minutes for
seltorexant 10 mg, and 48 minutes for seltorexant 20 mg.
For the key secondary endpoint, WASO-6 at Night 1, the mean
improvement from baseline at Night 1 was 15 minutes for placebo, 23
minutes for seltorexant 5 mg, 43 minutes for 10 mg, and 45 minutes
for 20 mg of seltorexant. Furthermore, multiple secondary endpoints
were also improved versus placebo and standard of care zolpidem,
which is available under the brand name Ambien.
Additional details are provided below.
“The findings from this study demonstrate that seltorexant
significantly improves sleep induction and prolongs sleep
duration,” said Professor Thomas Roth, Director of the Sleep
Disorders and Research Center at Henry Ford Hospital. “The
results also demonstrate that seltorexant showed a significantly
greater improvement in these sleep parameters compared to
zolpidem.
“In addition, the beneficial effects on LPS and WASO of
seltorexant on elderly patients in the study, in conjunction with a
favorable tolerability profile, suggest its potential benefit in
the large and growing population of elderly patients whose
prevalence of insomnia is higher than in younger patients, thus
representing an important therapeutic option,” said Professor
Roth.
Professor David Kupfer, Distinguished Professor Emeritus of
Psychiatry at the University of Pittsburgh School of Medicine and
board member of Minerva, said, “Based on these results and those
from the recent MDD2001 study, observations of seltorexant include
a clinically meaningful improvement in symptoms of depression in
patients not responding adequately to first line therapies (SSRIs
and SNRIs) and a clinically meaningful effect on insomnia in a wide
age range of patients.
“The demonstration of a significant benefit across a broad
spectrum of patients who suffer with depression and/or insomnia and
who have not responded adequately to existing therapies points to a
differentiated clinical profile and a new way to address an
underserved patient population” added Professor Kupfer.
“Seltorexant is a specific orexin-2 antagonist (SORA) rather
than a dual orexin receptor antagonist (DORA) and consequently has
a differentiated mechanism of action that may help address numerous
psychiatric disorders,” said Dr. Remy Luthringer, Executive
Chairman and Chief Executive Officer of Minerva. “Unlike existing
therapies, seltorexant is designed to mimic the natural sleep
process by inhibiting the brain mechanisms that promote excessive
wakefulness rather than by sedating patients through the activation
of the neurotransmitters that promote sleep.”
About the ISM 2005 trial
Study design:
This multicenter, phase 2b, double-blind, randomized,
parallel-group, active- and placebo-controlled, 17‑day (2 weeks of
active treatment) dose finding study was designed to evaluate the
efficacy and safety of seltorexant in both adult (18 to 64 years
old) and elderly (65 to 85 years old) subjects with insomnia
disorder without psychiatric co-morbidity. The study enrolled a
total number of 365 subjects, randomized in a 1:1:1:1:1 ratio to
receive one of 5 treatments: placebo, seltorexant 5 mg, seltorexant
10 mg, seltorexant 20 mg and zolpidem (5 or 10 mg based on the
local label). The randomization was stratified by region (United
States/Europe and Japan) and age group (adult and elderly).
Efficacy was evaluated at Night 1 (first drug administration)
and after 2 weeks of drug administration (Night 13). Safety was
evaluated throughout the study duration.
Polysomnography (PSG), an objective measure of sleep, was used
to evaluate the effect of seltorexant, placebo and zolpidem.
Primary and secondary objectives:
The primary objective was to evaluate the dose-response of three
doses of seltorexant (5, 10 and 20 mg daily) compared to placebo
using the primary endpoint, sleep onset as measured by LPS by PSG
at Night 1 (first drug administration).
The key secondary objective was to assess the effect of
seltorexant on the key secondary endpoint, WASO-6 by PSG at Night
1.
Other secondary objectives included:
- To assess the effect of seltorexant on LPS and WASO-6 at Night
13.
- To assess the effect of seltorexant compared to standard of
care treatment zolpidem on both LPS and WASO-6 at Nights 1 and
13.
Overall safety and tolerability were evaluated throughout the
study duration.
Both adult (18 to <65 years of age) and elderly (65 to 85
years of age) patients have been included in the study in order to
better understand age dependent efficacy and tolerability of
seltorexant and zolpidem.
Statistics:
The primary efficacy endpoint, LPS, was
evaluated at a 1-sided significance level of 0.05 using the MCP‑Mod
(Multiple Comparison Procedure-Modeling) approach to test for
dose-response. For all remaining statistical analyses of the
primary efficacy endpoint and for all other secondary efficacy
endpoints, mixed model for repeated measures (MMRM) or analysis of
covariance (ANCOVA) with no multiplicity adjustment were performed.
The primary and key secondary endpoints were log‑transformed before
the statistical analysis using ANCOVA/MMRM models. For all analyses
other than MCP-Mod, 2‑sided p-values are presented. When treatment
comparisons resulted in significant p‑values (p ≤0.050), these are
also presented below.
The pre-specified comparisons to zolpidem on
both endpoints and the overall safety and tolerability are also
included.
Results:
Of the 364 subjects that received study drugs, 32.4% were male.
The mean (SD) age was 57.8 (SD = 12.4) years, ranging
from 22 to 84 years. Subjects had a mean total insomnia
severity Index (ISI) score of 20.2 at baseline, indicative of
moderate to severe insomnia.
Primary endpoint:
All 4 pre-specified dose-response models showed a significant
dose-response relationship in LPS at Night 1, where the
adjusted 1-sided p-values were <0.001.
There was a significant separation from placebo of the 10 mg and
20 mg dose groups. The advantage in least squares (LS) mean
on changes from baseline of the seltorexant dose groups over
placebo at Night 1 were: 16.4 minutes for the 5 mg, 32.2 minutes
for the 10 mg (p ≤0.001), and 36.6 minutes for the 20 mg (p
≤0.001). Advantages over placebo were also observed at Night
13: 5.2 minutes for the 5 mg, 28.6 minutes for the 10 mg
(p ≤0.001), and 21.0 minutes for the 20 mg (p ≤0.001).
Secondary endpoints:
WASO-6 at Night 1 showed an advantage in LS mean on change from
baseline of the seltorexant dose groups over placebo of: 14.6
minutes for the 5 mg, 28.6 minutes for the 10 mg (p ≤0.005), and
28.6 minutes for the 20 mg (p ≤0.001). Advantages over
placebo were also observed at Night 13: 6.5 minutes for the 5
mg, 16.1 minutes for the 10 mg, and 21.5 minutes for the 20 mg (p
≤0.002).
WASO-6 was selected as the key secondary endpoint since
seltorexant has a short half-life, and in previous studies some
subjects awoke after 6-7 hours and did not feel the need for
additional sleep. Moreover, WASO-6 is often considered to be a
clinically relevant measure in sleep trials, since working adults
commonly do not elect to remain in bed asleep for an entire 8-hour
period.
Seltorexant 20 mg showed a greater improvement compared to
zolpidem for LPS at both Night 1 (10.5 minutes, p ≤0.010) and
Night 13 (12.1 minutes, p ≤0.036), while 10 mg only separated at
Night 13 (19.6 minutes, p ≤0.021). For WASO-6, the 20 mg dose
showed significantly greater improvement compared to zolpidem at
Night 13 (11.6 minutes, p ≤0.019). Zolpidem immediate release (IR),
which was administered as 5 or 10 mg according to the
country-by-country label, was chosen as active comparator and
showed superiority to placebo for both LPS and WASO-6 at Night 1
but not Night 13, demonstrating a known decrease of effect of
zolpidem over time.
Analyses of the LPS and WASO-6 were also performed by subgroups,
including age (adults and elderly), and overall these analyses were
consistent with the primary analysis. Additionally, the LPS results
were similar between the 2 age subgroups. WASO-6 had a better
response in the elderly (all 3 doses significantly separated from
placebo) compared to the adult population (only the 20 mg group
significantly separated from placebo).
Similar to previous clinical trials, seltorexant
showed a good safety and tolerability profile in both adult and
elderly patients. Overall seltorexant was well tolerated, with
treatment-emergent adverse events (TEAEs) similar to those observed
in previous studies. The overall incidence of adverse events in the
seltorexant treatment arms was low (33.8% in the combined
seltorexant group, with 40.3% in the 5 mg group, 31.5% in the 10 mg
group and 29.6% in the 20 mg group) and was lower than the rate
observed in the placebo group (49.3%) and zolpidem group (42.5%).
Most TEAEs were mild to moderate in intensity and resolved without
sequelae.
Conference Call Information:
Minerva Neurosciences will hold a conference call and live audio
webcast on June 24, 2019 at 8:30 a.m. Eastern Time to discuss the
results of this trial. To participate, please dial (877)
312-5845 (domestic) or (765) 507-2618 (international) and refer to
conference ID 1644578. To access the webcast, please go to
https://engage.vevent.com/rt/minervaneurosciencesinc~062419.
The live webcast can also be accessed under “Events and
Presentations” in the Investors and Media section of Minerva’s
website at ir.minervaneurosciences.com. The archived webcast
will be available on the website beginning approximately two hours
after the event for 90 days.
About Seltorexant (MIN-202)
Seltorexant is a selective orexin-2 receptor antagonist under
co-development by Janssen Pharmaceutica N.V., a Pharmaceutical
Company of Johnson & Johnson, and Minerva as adjunctive therapy
for MDD and for the treatment of insomnia disorder. The orexin
system in the brain is involved in the control of several key
functions, including metabolism, stress response and wakefulness.
This system promotes arousal (wakefulness) and is hypothesized to
play a role in excessive arousal, which occurs in patients with
insomnia and in subsets of patients with mood disorders, and to
have clinical utility in the treatment of such patients.
About Insomnia
According to the American Academy of Sleep Medicine,
approximately 30-35% of adults have brief symptoms of insomnia,
15-20% have short-term insomnia disorder (lasting less than three
months), and 10% have chronic insomnia, which occurs at least three
times per week for at least three months.1 Insomnia incurs a
significant economic cost on society, with estimates of $63.2
billion in lost productivity.2
Chronic insomnia can have a negative impact on health and can be
a common comorbidity of many medical conditions, including
diabetes, coronary heart disease, chronic obstructive pulmonary
disease, arthritis, fibromyalgia and other chronic pain
conditions. Individuals with insomnia disorder frequently
have a comorbid mental disorder, including depressive and anxiety
disorders.3
Age and gender are clearly identified demographic risk factors
for insomnia, with an increased prevalence in women and older
adults. Insomnia is commonly seen in elderly populations and is
associated with detrimental consequences for successful
aging.4 Sleep disturbances among the elderly are associated
with significant morbidity and mortality and increase the risk for
nursing home placement. These findings are particularly
relevant as the population of persons aged 65 years or older
continues to grow.
About Minerva Neurosciences
Minerva Neurosciences, Inc. is a clinical-stage
biopharmaceutical company focused on the development and
commercialization of a portfolio of product candidates to treat CNS
diseases. Minerva’s proprietary compounds include:
roluperidone (MIN-101), in clinical development for schizophrenia;
seltorexant (MIN-202 or JNJ-42847922), in clinical development for
insomnia and Major Depressive Disorder (MDD); MIN-117, in clinical
development for MDD; and MIN-301, in pre-clinical development for
Parkinson’s disease. Minerva’s common stock is listed on the
NASDAQ Global Market under the symbol “NERV.” For more
information, please visit http://www.minervaneurosciences.com.
About the Minerva & Janssen
collaboration
Minerva is developing seltorexant with Janssen Pharmaceutica
N.V., a Pharmaceutical Company of Johnson & Johnson. Under the
terms of the collaboration, Minerva has exclusive commercialization
rights to seltorexant and other orexin molecules for the treatment
of insomnia and all other indications including MDD in the Minerva
Territory (EU, Iceland, Lichtenstein, Switzerland & Norway).
Royalties on sales outside of the Minerva Territory are payable by
Janssen. Minerva pays royalties on sales (excluding sales of
products for the treatment of insomnia) within the Minerva
Territory.
Forward-Looking Safe Harbor Statement
This press release contains forward-looking statements which are
subject to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995, as amended. Forward-looking
statements are statements that are not historical facts, reflect
management’s expectations as of the date of this press release, and
involve certain risks and uncertainties. Forward-looking
statements include statements herein with respect to the timing and
scope of current clinical trials and results of clinical trials
with roluperidone, seltorexant, MIN-117 and MIN-301; the timing and
scope of future clinical trials and results of clinical trials with
these compounds; the clinical and therapeutic potential of these
compounds; our ability to successfully develop and commercialize
our therapeutic products; the sufficiency of our current cash
position to fund our operations; and management’s ability to
successfully achieve its goals. These forward-looking
statements are based on our current expectations and may differ
materially from actual results due to a variety of factors
including, without limitation, whether roluperidone, seltorexant,
MIN-117 and MIN-301 will advance further in the clinical trials
process and whether and when, if at all, they will receive final
approval from the U.S. Food and Drug Administration or equivalent
foreign regulatory agencies and for which indications; whether any
of our therapeutic products will be successfully marketed if
approved; whether any of our therapeutic product discovery and
development efforts will be successful; management’s ability to
successfully achieve its goals; our ability to raise additional
capital to fund our operations on terms acceptable to us; and
general economic conditions. These and other potential risks
and uncertainties that could cause actual results to differ from
the results predicted are more fully detailed under the caption
“Risk Factors” in our filings with the Securities and Exchange
Commission, including our Quarterly Report on Form 10-Q for the
quarter ended March 31, 2019, filed with the Securities
and Exchange Commission on May 6, 2019. Copies of reports
filed with the SEC are posted on our website at
www.minervaneurosciences.com. The forward-looking statements in
this press release are based on information available to us as of
the date hereof, and we disclaim any obligation to update any
forward-looking statements, except as required by law.
1
http://sleepeducation.org/news/2014/03/10/insomnia-awareness-day-facts-and-stats
2
https://aasm.org/insomnia-costing-u-s-workforce-63-2-billion-a-year-in-lost-productivity-study-shows/
3 https://www.ncbi.nlm.nih.gov/books/NBK19961/
4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978319/
Contact:
William B. BoniVP, Investor Relations/Corp.
CommunicationsMinerva Neurosciences, Inc.(617) 600-7376
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