ALISO VIEJO, Calif.,
Aug. 26, 2014 /PRNewswire/
-- Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR) today
announced the enrollment of the first patient into a phase II study
to evaluate the efficacy, safety and tolerability of AVP-786 for
the adjunctive treatment of major depressive disorder (MDD).
AVP-786 is a novel investigational drug consisting of a combination
of deuterium modified dextromethorphan and ultra-low dose
quinidine.
"There are millions of people with MDD who remain depressed
despite receiving standard antidepressant therapy," said
Maurizio Fava, MD, executive vice
chair, department of psychiatry at Massachusetts General Hospital,
Boston. "This is an important
clinical study given the properties of AVP-786 and the vast unmet
need in this area."
"With a unique, multifaceted mechanism of action encompassing
key neurotransmitter systems involved in regulation of mood,
AVP-786 has the potential to offer a new approach for the treatment
of patients with depression," said Joao
Siffert, MD, chief medical officer at Avanir
Pharmaceuticals.
About the MDD Study
This 10-week, multicenter,
randomized, double-blind, placebo-controlled proof-of-concept phase
II study will evaluate the efficacy and safety of AVP-786 in
patients with major depression who have had an inadequate response
to commonly prescribed antidepressants, including selective
serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine
reuptake inhibitors (SNRIs). The study is expected to enroll
approximately 200 patients at approximately 30 sites in
the United States. The study will
utilize a sequential parallel comparison design (SPCD); a design
developed ten years ago by Drs. Fava and Schoenfeld at
Massachusetts General Hospital and now increasingly utilized in
central nervous system (CNS) clinical trials. This study design is
intended to reduce placebo response rates, a phenomenon commonly
observed in depression trials. The primary efficacy measure
is the Montgomery-Asberg Depression Rating Scale (MADRS) total
score, a standard clinical measure of depression. Secondary outcome
measures include assessments of disease severity, activities of
daily living, and quality of life. Pharmacokinetics and standard
safety assessments will also be conducted.
Update on the Agitation in Alzheimer's Disease
Patients Study
The company expects to announce top-line
results from the Agitation in Alzheimer's disease study in late
September/early October 2014. The
objectives of this proof of concept study are to evaluate the
safety, tolerability, and efficacy of AVP-923 for the treatment of
agitation in Alzheimer's patients. The trial is a 10-week,
multicenter, randomized, double-blind, placebo-controlled study
utilizing a SPCD design intended to reduce placebo response rates.
Enrollment was completed with 220 Alzheimer's patients in
the United States. Eligible
patients were initially randomized 3:4 to receive either AVP-923
(dose escalated from DM 20mg/ Q 10mg to DM 30mg/ Q 10mg) or
placebo. At the end of week five, patients who initially received
placebo were stratified according to their response to treatment
and subsequently re-randomized 1:1 to receive either AVP-923 or
placebo for the remainder of the study (an additional 5 weeks of
treatment). Patients who initially received AVP-923 continued to
receive AVP-923 DM 30mg/ Q 10mg for the remainder of the study. The
main efficacy measure is the agitation/aggression subscale of the
Neuropsychiatric Inventory or NPI. The primary endpoint follows a
standard analysis of SPCD by combining the change from baseline to
week 5 (full analysis population) and change from week 5 to week 10
on the NPI agitation/aggression domain (patients who were
considered "non-responders" to placebo during the initial 5 weeks).
Secondary outcome measures include global assessments of disease
severity, other neuropsychiatric symptoms, cognition, activities of
daily living, quality of life and caregiver strain. Standard safety
assessments will also be conducted.
About Major Depressive Disorder
Major depressive
disorder (MDD) is a condition in which patients exhibit depressive
symptoms, such as a depressed mood or a loss of interest or
pleasure in daily activities consistently for at least a two-week
period, and demonstrate impaired social, occupational, educational
or other important functioning. An estimated 16 million people in
the U.S. suffer from MDD in a given year. As many as two-thirds of
patients who are diagnosed with MDD do not experience adequate
improvement with initial antidepressant therapy.
About AVP-786
AVP-786, the company's next-generation
compound, is a novel investigational drug product consisting of a
combination of deuterium modified dextromethorphan (an
uncompetitive NMDA receptor antagonist, sigma-1 receptor agonist
and inhibitor of the serotonin transporter (SERT) and
norepinephrine (NET) transporter) and ultra-low dose quinidine (a
CYP2D6 enzyme inhibitor). Incorporation of deuterium into specific
positions of the dextromethorphan molecule strengthens the chemical
bonds and reduces susceptibility to enzyme cleavage and first pass
metabolism, but without altering its pharmacology. By having a
lower metabolism rate, deuterium modified DM in AVP-786 requires a
substantially lower level of the metabolic inhibitor quinidine in
the formulation. This may result in a reduced potential for drug
interactions, while maintaining therapeutic efficacy. AVP-786 is an
investigational drug not approved by the FDA.
About AVP-923
AVP-923 is a combination of two
well-characterized compounds, the active CNS ingredient
dextromethorphan hydrobromide (an uncompetitive NMDA receptor
antagonist, sigma-1 receptor agonist and inhibitor of the serotonin
transporter (SERT) and norepinephrine (NET) transporter) plus
low-dose quinidine sulfate (a CYP2D6 enzyme inhibitor), which
serves to increase the bioavailability of dextromethorphan. AVP-923
is being studied in several ongoing company sponsored Phase II
clinical trials including agitation in Alzheimer's disease,
levodopa-induced dyskinesia in Parkinson's disease, and multiple
investigator initiated studies. AVP-923 is an investigational drug
not approved by the FDA.
About Avanir Pharmaceuticals, Inc.
Avanir
Pharmaceuticals, Inc. is a biopharmaceutical company focused on
bringing innovative medicines to patients with central nervous
system disorders of high unmet medical need. As part of our
commitment, we have extensively invested in our pipeline and are
dedicated to advancing medicines that can substantially improve the
lives of patients and their loved ones. For more information about
Avanir, please visit www.avanir.com.
AVANIR® is a trademark or registered trademark of Avanir
Pharmaceuticals, Inc. in the United
States and other countries.
©2014 Avanir Pharmaceuticals, Inc. All Rights Reserved.
Forward Looking Statements
Except for the
historical information contained herein, the matters set forth in
this press release, including statements regarding Avanir's plans,
potential opportunities, financial or other expectations,
projections, goals objectives, milestones, strategies, market
growth, timelines, legal matters, product pipeline, clinical
studies, product development and the potential benefits of its
commercialized products and products under development are
forward-looking statements within the meaning of the "safe harbor"
provisions of the Private Securities Litigation Reform Act of 1995.
These forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially,
including the risks and uncertainties associated with, the market
demand for and acceptance of Avanir's products domestically and
internationally, research, development and commercialization of new
products domestically and internationally, including the risks and
uncertainties associated with meeting the objectives of the study
of AVP-786, and AVP-923, including, but not limited to, risks
relating to the successful development of these investigational
drugs, delays or failures in enrollment, or delays in the release
of study results, whether preclinical and clinical results for
AVP-786 or AVP-923 will be predictive of future clinical study
results; whether future clinical trials for AVP-786 will be
completed on time or at all, potential changes in cost, scope and
duration of the clinical studies for AVP-786, whether AVP-786 can
offer a new approach for treatment of MDD, obtaining additional
indications for commercially marketed products domestically and
internationally, obtaining and maintaining regulatory approvals
domestically and internationally, and other risks detailed from
time to time in the Company's most recent Annual Report on Form
10-K and other documents subsequently filed with or furnished to
the Securities and Exchange Commission. These forward-looking
statements are based on current information that may change and you
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this press release.
All forward-looking statements are qualified in their entirety by
this cautionary statement, and the Company undertakes no obligation
to revise or update any forward-looking statement to reflect events
or circumstances after the issuance of this press release.
Avanir Investor & Media Contact
Ian Clements, PhD
ir@avanir.com
+1 (949) 389-6700
Brewlife Media Contact
Kelly
France
kfrance@brewlife.com
+1 (415) 946-1076
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SOURCE Avanir Pharmaceuticals, Inc.