Full Press Release Details
Minerva Neurosciences Announces Achievement of Primary and Key Secondary Objectives in Phase 2b Clinical Trial of
Seltorexant (MIN-202) in Insomnia
WALTHAM, Mass., June 24, 2019 (GLOBE NEWSWIRE) 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
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
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:
Overall safety and tolerability were evaluated throughout the study
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.
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.
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
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
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.
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. Insomnia incurs a significant economic
cost on society, with estimates of $63.2 billion in lost productivity.
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.
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. 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.
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