ALISO VIEJO, Calif.,
Oct. 8, 2014 /PRNewswire/
-- Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR)
today announced that data from the phase II trial evaluating
AVP-923 for the treatment of agitation in patients with Alzheimer's
disease (AD) and the results of the phase IV PRISM II study
evaluating NUEDEXTA® (dextromethorphan hydrobromide/quinidine
sulfate) for the treatment of pseudobulbar affect (PBA) in patients
with AD will be presented at the American Neurological
Association's (ANA) Annual Meeting being held at the Marriott
Waterfront Hotel in Baltimore,
Maryland, October 12-14, 2014.
Poster Presentation Details
Title: Dextromethorphan/Quinidine (AVP-923) Efficacy and Safety
for Treatment of Agitation in Alzheimer's disease (AD): Results
from a Phase II Study (NCT01584440)
Poster Number: M1336WIP
Presentation Date/Time: Monday, October 13, 2014; 5:30 p.m. – 7:00 p.m.
ET
Title: Safety, Tolerability, and Effectiveness of
Dextromethorphan/Quinidine for Pseudobulbar Affect in Patients with
Alzheimer's Disease/Dementia: PRISM-II
Poster Number: M1334WIP
Presentation Date/Time: Monday, October 13, 2014; 5:30 p.m. – 7:00 p.m.
ET
About Agitation in Alzheimer's Disease Phase II 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 were also
conducted.
About PRISM II
The objectives of the study are to
evaluate the safety, tolerability, and effectiveness of NUEDEXTA
capsules containing 20 mg dextromethorphan (DM) and 10 mg quinidine
(Q) for treatment of PBA in patients with prevalent neurological
conditions including Alzheimer's disease/dementia, stroke and
traumatic brain injury over a 12 week period.
PRISM II is a nationwide, open-label, multicenter, 12-week study
enrolling up to approximately 450 patients at approximately 100
study centers. The Alzheimer's disease/dementia cohort is fully
enrolled at 134 patients. Eligible patients are aged >18 years
with a clinical diagnosis of PBA and baseline score >13 on the
Center for Neurologic Study-Lability Scale (CNS-LS), a PBA rating
instrument. Patients with TBI due to a penetrating head injury are
excluded. Patients are treated with DMQ 20/10 mg twice daily. The
primary endpoint is change from baseline in CNS-LS score.
Determination of effectiveness is based on a comparison of CNS-LS
change in PRISM II with results of previous Phase III studies.
Additional outcomes measures include: number of PBA episodes
(laughing and/or crying); Mini-Mental State Examination; quality of
life; Clinician and Patient Global Impression (CGIC; PGIC);
patients' satisfaction with treatment; Patient Health Questionnaire
(PHQ-9) (to evaluate mood symptoms), and the Neurobehavioral
Functioning Inventory for TBI patients. Safety measures include
monitoring of adverse events, concomitant medication usage, and
vital signs.
About PBA
PBA is a neurologic condition characterized
by uncontrollable, disruptive laughing and/or crying outbursts that
are often contrary or exaggerated to the patient's inner mood
state. As a result, many of those afflicted with PBA show
significant impairment on standard measures of health status, and
impairments in occupational and social function, often leading to
social isolation. PBA occurs secondary to a variety of neurologic
conditions such as traumatic brain injury (TBI), multiple sclerosis
(MS), amyotrophic lateral sclerosis (ALS), Parkinson's
disease, stroke and Alzheimer's disease. When these disorders
damage areas of the brain that regulate normal emotional
expression, they can lead to uncontrollable, disruptive episodes of
crying or laughing. For more information about PBA, please
visit www.pbafacts.com
The CNS-LS has been validated in ALS and MS patients.
About NUEDEXTA
NUEDEXTA is an innovative combination
of two well-characterized components; dextromethorphan hydrobromide
(20 mg), the ingredient active in the central nervous system, and
quinidine sulfate (10 mg), a metabolic inhibitor enabling
therapeutic dextromethorphan concentrations. NUEDEXTA acts on
sigma-1 and NMDA receptors in the brain, although the mechanism by
which NUEDEXTA exerts therapeutic effects in patients with PBA is
unknown.
NUEDEXTA Important Safety Information
NUEDEXTA is
indicated for the treatment of pseudobulbar affect (PBA). PBA
occurs secondary to a variety of otherwise unrelated neurological
conditions, and is characterized by involuntary, sudden, and
frequent episodes of laughing and/or crying. PBA episodes typically
occur out of proportion or incongruent to the underlying emotional
state.
Studies to support the effectiveness of NUEDEXTA were performed
in patients with amyotrophic lateral sclerosis (ALS) and multiple
sclerosis (MS). NUEDEXTA has not been shown to be safe and
effective in other types of emotional lability that can commonly
occur, for example, in Alzheimer's disease and other dementias.
NUEDEXTA and certain other medicines can interact, causing
serious side effects. If you take certain drugs or have certain
heart problems, NUEDEXTA may not be right for you.
NUEDEXTA causes dose-dependent QTc prolongation. When initiating
NUEDEXTA in patients at risk for QT prolongation and torsades de
pointes, electrocardiographic (ECG) evaluation should be conducted
at baseline and 3-4 hours after the first dose.
The most common adverse reactions are diarrhea, dizziness,
cough, vomiting, asthenia, peripheral edema, urinary tract
infection, influenza, increased gamma-glutamyltransferase, and
flatulence. NUEDEXTA may cause dizziness.
These are not all the risks from use of NUEDEXTA. Please refer
to full Prescribing Information at www.NUEDEXTA.com.
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.
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® and NUEDEXTA® are registered trademarks owned
by Avanir Pharmaceuticals, Inc. All other trademarks are
the property of their respective owners.
©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 NUEDEXTA in the PRISM II study including, but not limited
to, risks relating to delays or failures in enrollment, or delays
in the release of study results, 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, PhD
kfrance@brewlife.com
+1 (415) 946-1076
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SOURCE Avanir Pharmaceuticals, Inc.