Advancing a
new potential therapeutic paradigm for the treatment of negative
symptoms, a key unmet need in schizophrenia and other brain
diseases
Company to
host conference call on May 16, 2017 at 10:30 a.m. eastern
time
WALTHAM, Mass., May 15, 2017 (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
plans for its Phase 3 and Phase 4 clinical development of MIN-101,
a drug targeting negative symptoms in schizophrenia patients.
Following a recent "end-of-Phase 2" meeting with the U.S. Food and
Drug Administration (FDA), the Company's next step is the planned
initiation of a pivotal Phase 3 trial with MIN-101 in the second
half of 2017.
"We are very excited to be taking MIN-101 into a
pivotal Phase 3 trial, which has the potential to identify a new
approach to the treatment of schizophrenia and improve the quality
of life for millions of patients," said Dr. Remy Luthringer,
president and chief executive officer of Minerva. "Our
development strategy for MIN-101 is driven by the recognition that,
while positive symptoms are present intermittently and are a
hallmark of early schizophrenia, negative symptoms persist and
worsen over the lifetimes of the majority of schizophrenic
patients, severely limiting their social and vocational
reintegration over the longer term. No drugs are currently
approved to treat the negative symptoms of schizophrenia or
negative symptoms present in other conditions, including
developmental disorders, affective disorders and neurodegenerative
disorders."
Data from the Company's Phase 2b trial with
MIN-101 have informed the design of the Phase 3 trial. Key
findings from the Phase 2b trial include observations of a direct
effect on negative symptoms (rather than an indirect or pseudo
effect linked to improvements in other symptoms and/or a different
side effect profile). The data also support the durability of
this effect through the entire 36-week duration of the trial, which
included a 12-week double-blind, placebo-controlled core phase and
a 24-week, open-label extension phase. The specificity of
MIN-101's therapeutic effects on negative symptoms was validated by
the stability of positive symptoms observed over the entire
duration of treatment and a side effect profile comparable to
placebo, particularly as it relates to extra-pyramidal symptoms
(EPS). The Company believes that the unique pharmacological profile
of MIN-101 (sigma 2 and serotonin 5HT2a receptor
antagonism) and the absence of direct binding to post-synaptic
dopamine receptors may explain its specific effects on negative
symptoms.
Key elements of the Phase 2b trial that will be
incorporated into the Phase 3 trial include:
- improvement in negative symptoms as
the primary endpoint;
- monotherapy administration of
MIN-101 and no co-administration with atypical antipsychotics at
any stage in the study;
- recruitment of patients with
moderate-to-severe negative symptoms expressed as a specified
minimum threshold baseline score on the Positive and Negative
Syndrome Scale (PANSS) negative sub-scale; and
- a 12-week double-blind, randomized,
placebo-controlled core phase followed by an open-label extension
phase.
Two doses of MIN-101 or placebo will be
administered during the double-blind phase of the Phase 3 trial,
which will last 12 weeks, followed by an optional 36-week extension
phase in which all patients will receive MIN-101.
Approximately 500 patients will be enrolled at approximately 60
clinical sites across the U.S. and Europe, with a significant
number of patients recruited at U.S. sites. The Company believes
that the efficacy data from the Phase 3 trial, if positive, in
addition to the Phase 2b data, may form the basis for the future
submission of a New Drug Application (NDA) for MIN-101 to the
FDA. Furthermore, at the conclusion of the extension period
of the Phase 3 trial, the overall number of patients exposed to
MIN-101 since the initiation of its clinical development is
expected to provide sufficient long-term safety data to support an
NDA.
The primary Phase 3 trial endpoint of improvement
in negative symptoms at 12 weeks will be measured by the PANSS
negative sub-scale score using the Marder factor, a widely
recognized instrument for quantifying severity of negative
symptoms. The Marder negative sub-score is similar to the White
negative sub-score used in the Phase 2b trial. The two
factors differ from each other in that the Marder score has
eliminated four items and added one on active social avoidance (G16
item). The Company is employing the Marder scale because this
item has been shown to be well correlated with patients' overall
functional outcome.
The Company's Phase 3 trial design is intended to
replicate the experience of "real world" clinical practice in
schizophrenia. Many patients are dissatisfied and not well
served by continuous antipsychotic treatment as evidenced by poor
compliance with medications. Recent scientific literature points
toward the fact that indefinite antipsychotic maintenance treatment
in schizophrenic patients (provided by post-synaptic blockade of
dopamine receptors) may be responsible for poor long term
functional outcomes in addition to well described side effects,
including EPS, weight gain, sedation and prolactin increase.
In summary, the Phase 3 trial will seek to confirm clinically
meaningful effects on patients' negative symptoms and to determine
whether patients can stay stable in terms of positive symptoms
without experiencing the adverse effects of antipsychotics.
Treatment of the positive symptoms of
schizophrenia represents a large market estimated at more than $6.2
billion in 2016. Epidemiological studies suggest that an estimated
60 percent of schizophrenia patients present with negative
symptoms, which are the basis of poor functional outcome and thus
represent a significant unmet medical need and burden for patients,
families and society.
In Phase 4 development, the Company plans to
conduct additional trials to expand the profile of MIN-101.
These may potentially include a study comparing the rate of
psychosis relapses in patients treated with MIN-101, standard of
care with antipsychotics or placebo. In addition, the Company
may conduct a trial in adolescents at high risk for schizophrenia
who during the prodromal phase manifest negative
symptoms.
While negative symptoms are a core component of
schizophrenia and predict poor functional capacity, they are not
specific to that disease but are also recognized as a hallmark of
other diseases. These include neurodegenerative disorders
such as Alzheimer's disease, Parkinson's disease, mood disorders,
schizophrenia spectrum disorders and autism spectrum
disorders. The Company plans to assess these indications as
expansion options for MIN-101 in a development program beyond the
planned Phase 3 study in schizophrenia.
Conference call
information
The Company will host a conference call and live
webcast tomorrow, May 16, 2017 at 10:30 a.m. Eastern Time to
discuss its plans for Phase 3 development of MIN-101 and
beyond. The topics outlined above will be addressed. To
participate, please dial 800-263-8506 (domestic) or 719-457-2605
(international) and refer to conference ID # 1545954. Leading
the call will be Dr. Remy Luthringer, president and chief executive
officer of Minerva. Also participating will be key opinion
leaders in the field of schizophrenia, including Dr. Philip Harvey,
Leonard M. Miller Professor of Psychiatry and director of the
Division of Psychology at the University of Miami Miller School of
Medicine, and Dr. Brian Kirkpatrick, chair of the Department of
Psychiatry and Behavioral Sciences at the University of Nevada
School of Medicine. Both Dr. Harvey and Dr. Kirkpatrick are
internationally recognized for their work in the field of
schizophrenia and negative symptoms, and they participated in the
recent meeting between the FDA and Minerva as consultants to the
Company.
The webcast can be accessed under "Events and
Presentations" in the Investors and Media section of Minerva's
website beginning approximately two hours after the event for 90
days.
About schizophrenia and the
impact of negative symptoms
Schizophrenia remains among the top ten disabling
conditions worldwide for young adults and affects more than 21
million people worldwide. According to Datamonitor, an
independent market research firm, in 2016 approximately
3.3 million people suffered from schizophrenia in the United
States, Japan and the five major European Union markets of France,
Germany, Italy, Spain and the United Kingdom.
Although positive psychotic symptoms are
characteristic of schizophrenia, negative symptoms constitute one
of the main sources of burden of illness, represent an important
treatment target and are a major cause of the poor vocational and
social capabilities of these patients. These symptoms, which
include a-motivation, avolition, lack of initiative, and restricted
personal interaction, are associated with poor psychosocial
functioning.
In the majority of schizophrenia patients, acute
positive symptoms remit due to treatment with antipsychotics
(dopamine-blocking drugs) or spontaneously. Antipsychotic drugs
also reduce the risk for recurrence of psychosis. However, many
patients maintain remission of psychosis without antipsychotic
dopamine blocking drugs. Nevertheless, they continue to
suffer negative symptoms, for which no FDA-approved treatments are
specifically indicated.
About MIN-101
MIN-101 is a drug candidate with equipotent
affinities for
sigma2 and 5-hydroxytryptamine-2A (5-HT2A) and
lower affinity at A1-adrenergic receptors. MIN-101 has no direct
dopaminergic post-synaptic blocking effects, known to be involved
in some side effects like extrapyramidal symptoms, sedation,
prolactin increases and weight gain.
The Phase 2b trial with MIN-101, announced in 2016
and presented at the annual meeting of the American College of
Neuropsychopharmacology, met its primary endpoint of statistically
significant improvement in negative symptoms as measured by the
PANSS pentagonal structure model and in the higher dose showed
statistically significant benefit in multiple secondary endpoints
that included general psychopathology.
About Minerva
Neurosciences
Minerva Neurosciences, Inc. is a clinical-stage
biopharmaceutical company focused on the development and
commercialization of a portfolio of products to treat CNS
diseases. Minerva's proprietary compounds include: MIN-101,
in clinical development for schizophrenia; MIN-117, in clinical
development for major depressive disorder (MDD); MIN-202
(JNJ-42847922), in clinical development for insomnia and 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.
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 results of future clinical
milestones with MIN-101, including the planned Phase 3 trial of
MIN-101, the timing and scope of future clinical trials and results
of clinical trials with this compound; the potential for a single
Phase 3 trial with supportive Phase 2b results to support the basis
for an NDA; the timing and outcomes of future interactions with
U.S. and foreign regulatory bodies; our ability to successfully
develop and commercialize MIN-101; 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 MIN-101 will advance further
in the clinical trials process and whether and when, if at all, it
will receive final approval from the U.S. Food and Drug
Administration or equivalent foreign regulatory agencies and for
which indications; whether the results of future clinical trials of
MIN-101, if any, will be consistent with the results of past
clinical trials; whether MIN-101 will be successfully marketed if
approved; whether any of our therapeutic product discovery and
development efforts will be successful; our ability to achieve the
results contemplated by our co-development agreements; 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, 2017, filed with
the Securities and Exchange Commission on May 4,
2017. 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.