ALISO VIEJO, Calif.,
Sept. 15, 2014 /PRNewswire/
-- Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR) today
announced positive results from its phase II clinical trial
evaluating the safety and efficacy of AVP-923 for the treatment of
agitation in patients with Alzheimer's disease. Treatment with
AVP-923 was associated with significantly reduced agitation as
measured by the primary endpoint, the agitation/aggression domain
score of the neuropsychiatric inventory (NPI) compared to placebo
(p=0.00008). The reduction in agitation was observed in both
stage 1 (p=0.0002) and stage 2 (p=0.021) of the Sequential Parallel
Comparison study design.
In addition, improvements were also seen in a majority of the
secondary endpoints including the NPI total score (p=0.014),
clinical global impression of change-agitation (p=0.0003), patient
global impression of change (p=0.001) and measures of caregiver
burden (p≤0.05).
"This is an exciting advancement in Alzheimer's disease
research," said Jeffrey Cummings,
MD, director of the Cleveland Clinic Lou Ruvo Center for Brain
Health and chair of the study steering committee. "Dementia-related
neuropsychiatric symptoms such as agitation are extremely
distressing to patients and their families."
"A potential new treatment option that could alleviate agitation
or aggression as a result of Alzheimer's disease would have a
significant impact on the daily life of these patients and of their
caregivers," added Constantine
Lyketsos, MD, director of the Johns Hopkins Memory and
Alzheimer's Treatment Center and also a member of the study
steering committee.
"With no FDA approved drugs for the treatment of agitation in
Alzheimer's disease, we believe these results represent a
breakthrough for patients," said Joao
Siffert, MD, chief medical officer at Avanir. "We are
extremely excited with the prospect of bringing a potential
treatment that can provide clinically meaningful relief to these
patients and reduce caregiver burden. These study results represent
the second neuropsychiatric disorder where AVP-923 has shown
benefit and lends support for further advancement of our research
programs into related disorders."
Data from this phase II study will be presented at the American
Neurological Association's (ANA) 2014 Annual Meeting in
Baltimore, MD, October, 12-14,
2014.
Based on these results Avanir plans to request a meeting with
both the U.S. Food and Drug Administration (FDA) and the European
Medicines Agency (EMA) with the intention of discussing advancement
of its dextromethorphan programs into pivotal studies for the
treatment of agitation in patients with Alzheimer's disease.
AVP-923 was found to be generally well-tolerated in this phase
II study. The most common adverse reactions were falls, diarrhea,
and urinary tract infection occurring in less than 10 percent of
patients. There was a low patient discontinuation rate and there
were no serious adverse events that were deemed treatment related
by the investigators. AVP-923 is known to have certain risks (see
'About AVP-923' section below).
About the Study Design
The objectives of this phase II
study were to evaluate the safety, tolerability, and efficacy of
AVP-923 for the treatment of agitation in Alzheimer's patients. The
trial was 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 5, 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 (stage 1: full
analysis population) and change from week 5 to week 10 (stage 2) 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 Agitation in Alzheimer's Disease
An estimated
six million Americans have Alzheimer's disease, a number that has
doubled since 1980 and is expected to be as high as 16 million by
2050. Alzheimer's disease is generally characterized by cognitive
decline, impaired performance of daily activities, and behavioral
disturbances. Behavioral and psychiatric symptoms develop in as
many as 60% of community-dwelling dementia patients and in more
than 80% of patients with dementia living in nursing homes; as the
disease progresses the risk of such complications approaches
100%. Dementia-related behavioral symptoms, including agitation,
can be extremely distressing to the individual, the family, and
caregivers. These behavioral disturbances have been associated with
more rapid cognitive decline, institutionalization, and increased
caregiver burden.
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 an investigational drug not approved by the FDA. AVP-923 is
known to have certain cardiovascular risks and drug-drug
interactions. Patients with history of certain cardiovascular risks
and on certain drugs were excluded from the study.
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 delays in the
release of study results, whether preclinical and clinical results
for AVP-923 or other dextromethorphan drug products will be
predictive of future clinical study results, whether regulatory
agencies domestically and internationally will discuss advancement
of one or more programs into pivotal studies, whether study data
will be accepted for presentation and/or publication and whether a
drug candidate can ultimately be successfully developed for
commercialization, whether future clinical trials will be completed
on time or at all, potential changes in cost, formulation, scope
and duration of the clinical studies, obtaining additional
indications for commercially marketed products domestically and
internationally, obtaining and maintaining regulatory approvals
domestically and internationally, whether new drugs can be
successfully commercialized, 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, PhD
kfrance@brewlife.com
+1 (415) 946-1076
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SOURCE Avanir Pharmaceuticals, Inc.