Advancing a new potential therapeutic
paradigm for the treatment of negative symptoms, a key unmet need
in schizophrenia and other brain diseases
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
α1-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.
Contact:
William B. Boni
VP, Investor Relations/
Corp. Communications
Minerva Neurosciences, Inc.
(617) 600-7376
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