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
positive results from a Phase 2b clinical trial of seltorexant
(MIN-202) as adjunctive therapy to antidepressants in adult
patients with major depressive disorder (MDD) who have responded
inadequately to selective serotonin reuptake inhibitors (SSRIs)
and/or serotonin-norepinephrine reuptake inhibitors (SNRIs).
In this dose finding study, the 20 milligram (mg) dose of
seltorexant, under co-development with Janssen Pharmaceutica NV,
showed a statistically significant improvement in the MADRS
(Montgomery-Asberg Depression Rating Scale) score compared to
placebo. The least squares mean (LS mean) difference from placebo
of the change in MADRS total score at the end of week 6 was 3.1 for
the 20 mg dose of seltorexant, and the 2-sided p-value was 0.083,
which is below the pre-specified 2-sided type I error level of
0.1.
After three weeks of treatment, seltorexant at the 20 mg dose
also showed a statistically significant improvement over placebo,
highlighting its ability to improve mood symptoms over a short
period of time. In addition, a key secondary outcome measure, which
was based on patient stratification according to baseline insomnia
severity index (ISI), showed an even greater difference from
placebo for the seltorexant 20 mg arm in patients with clinically
significant insomnia (ISI ≥ 15) with LS mean difference versus
placebo of 4.9 on the MADRS total score and a 2-sided p-value of
0.050 compared to the overall patient population in this trial.
The 40 mg dose, to which further enrollment was stopped
following the interim analysis, showed an improvement in the MADRS
total score versus placebo at the end of week 6 but did not reach
statistical significance. Results for the 10 mg dose were not
interpretable due to the small sample size of patients assigned to
this dose.
Seltorexant was well tolerated, and adverse events recorded were
similar to those observed in previous studies and similar to or
lower than the rate observed in the placebo group.
“Results of this study represent the first clinical observation
in a large, late-stage study that a selective orexin molecule can
achieve a positive effect as an adjunctive treatment in patients
with MDD who have an inadequate response to SSRIs and SNRIs,” said
Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer
of Minerva. “These findings, if confirmed in Phase 3 studies,
point to a completely novel approach which would give hope to
patients and to the professionals who treat them for a potential
new treatment for MDD with an improved safety profile compared to
existing therapies. Around 60%-70% of patients diagnosed and
treated with first-line therapies, including SSRIs and/or SNRIs, do
not experience adequate treatment response, and seltorexant
potentially represents a unique opportunity to improve treatment
response rates safely in most of these patients.”
Dr. Luthringer added, “The top line results from a separate
Phase 2b trial of seltorexant in insomnia, now completely enrolled,
are expected to be announced later this quarter and will add to the
body of clinical data with seltorexant in insomnia and MDD.”
About the Phase 2b study (aMDD2001)
The multicenter, double-blind, randomized, parallel-group,
placebo-controlled, 6-week adaptive dose-finding study consisted of
three phases: a screening phase lasting up to 4 weeks, a 6-week
double-blind treatment phase and a 2-week post-treatment follow-up
phase. In total, 287 adult patients were enrolled at 84 clinical
sites in the U.S., Europe and Japan. The study was powered for a
2-sided type I error level of 0.100. The objectives of the study
were to evaluate which dose(s) of seltorexant shows a statistically
significant difference from placebo on mood using the MADRS scale
after 6 weeks of treatment, to assess the influence of insomnia on
the observed effects on mood, and to further evaluate the overall
safety and tolerability of seltorexant.
At commencement of study enrollment, subjects were randomly
assigned to receive 1 of 3 treatments in a 2:1:1 ratio of
seltorexant to placebo (20 mg, 40 mg). After a pre-planned
interim analysis (IA), subjects were randomly assigned to receive 1
of 3 treatments in a 3:3:1 ratio of seltorexant to placebo (10 mg,
20 mg). The randomization was stratified by region (U.S., Europe,
and Japan) and by baseline insomnia status (insomnia severity
index, or ISI, score ≥15 versus <15). A mixed model for repeated
measures (MMRM) analysis was preplanned (analysis of response by
each dose, compared to placebo).
Seltorexant and the Major Depressive Disorder (MDD)
landscape
Major Depressive Disorder (MDD) is one of the most commonly
encountered mental disorders, with a prevalence rate in the United
States of 4.7%. Globally, more than 300 million people of all
ages suffer from depression. Depression is the leading cause
of disability worldwide and is a major contributor to the overall
global burden of disease. It is associated with significant
comorbid medical conditions that include diabetes, hypertension and
cardiovascular disease, and there is an increased risk of early
mortality in patients with MDD.
Among those patients suffering from MDD disorders, some do not
respond adequately to either SSRIs or SNRIs. Inadequate response to
these pharmacological treatments is a major challenge to worldwide
public health. Although it is widely considered that current
intervention benefits approximately 60% of MDD patients, only about
30% to 40% of patients show full remission of their symptoms as
defined by the MacArthur criteria (for example, a 17-item Hamilton
Depression Rating Scale (HDRS) score < 8).
To overcome the lack of adequate response, the use of atypical
antipsychotics as adjunctive therapy for the management of patients
with an inadequate response to standard of care has become one of
the most widely used therapeutic strategies. Use of adjunctive
atypical antipsychotics for MDD is associated with significant side
effects such as weight gain, akathisia, and sedation. Several
other approaches have been evaluated but, in most cases, with
non-conclusive results.
Innovative approaches are needed to improve current response
rates to existing treatments. The orexin system is viewed as a
pivotal system in the brain and its effects classically include
promotion of feeding, maintaining homeostasis, arousal, modulation
of sleep-wake circadian cycles and motivation. These functions
are mediated via two orexin receptors, ORX1 and ORX2.
Seltorexant is the most advanced specific ORX2 molecule in
clinical development with antagonistic activity when binding to its
receptor. Seltorexant is currently being developed in two
indications, specifically insomnia without associated psychiatric
disorders and MDD in patients who have an inadequate response to
SSRIs and SNRIs. Previous clinical trials have indicated that
seltorexant might be useful in both indications.
About Seltorexant (MIN-202)
Seltorexant is a selective orexin-2 receptor antagonist under
co-development by Janssen Pharmaceutica NV 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
subsets of patients with mood disorders, and to have clinical
utility in the treatment of such patients.
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 MDD; MIN-117, in clinical development for major
depressive disorder (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 www.minervaneurosciences.com.
About the Minerva & Janssen
collaboration
Minerva is developing seltorexant with Janssen Pharmaceutica, a
Johnson & Johnson company. 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.
Minerva has no financial obligations for development costs until
completion of the Phase 2b development milestone. Minerva has
strategic control of matters relating to the clinical development
of seltorexant for insomnia.
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.
Contact:
William B. BoniVP, Investor Relations/Corp.
CommunicationsMinerva Neurosciences, Inc.(617) 600-7376
Minerva Neurosciences (NASDAQ:NERV)
Historical Stock Chart
From Mar 2024 to Apr 2024
Minerva Neurosciences (NASDAQ:NERV)
Historical Stock Chart
From Apr 2023 to Apr 2024