Avanir Pharmaceuticals Announces Presentation of Positive Early Results from
PRISM II Study
--Interim Results Show NUEDEXTA Provides Meaningful Reduction of PBA Episodes
and is Generally Well Tolerated in Alzheimer's Disease/Dementia Population--
ALISO VIEJO, Calif., July 16, 2014
ALISO VIEJO, Calif., July 16, 2014 /PRNewswire/ --Avanir Pharmaceuticals,
Inc. (NASDAQ: AVNR) today announced interim data from the phase IV PRISM II
study showing that treatment with NUEDEXTA^® substantially reduced symptoms of
pseudobulbar affect (PBA) in patients with Alzheimer's disease/dementia. PBA
is a distressing neurologic condition characterized by sudden and uncontrolled
outbursts of laughing and/or crying in patients with neurologic disease and
injury. A standard quality of life measure also showed clear improvement over
the 3-month treatment period. The data were presented today, Wednesday, July
16, 2014 at the Alzheimer's Association International Conference (AAIC), being
held at the Bela Center in Copenhagen, Denmark.
"These initial data showing reduced symptoms of pseudobulbar affect (PBA) in
patients with PBA secondary to Alzheimer's and dementia are consistent with
the benefits we saw in the pivotal phase III study, in PBA patients with ALS
and MS, and provide further evidence that NUEDEXTA may offer relief from the
debilitating episodes of PBA," said Joao Siffert, MD, chief medical officer at
Avanir. "PRISM II has now completed enrollment of patients with dementia and
continues to enroll patients with stroke and traumatic brain injury, two
additional important causes of PBA. We look forward to reporting data from
these additional cohorts later this year."
"PBA can have a devastating impact on the lives of patients that are already
suffering with neurologic disorders such as Alzheimer's disease and other
dementias," said Stephen D'Amico, MD, CMD, medical director at Cornerstone
Medical Group, Tennessee. "The reduction in PBA symptoms and improvement in
quality of life measures seen in this study are evidence of the clinically
meaningful impact that treatment with NUEDEXTA may have."
PRISM II assessed the safety and efficacy of NUEDEXTA in treating PBA in
patients with Alzheimer's disease/dementia, stroke and TBI. While the
Alzheimer's disease/dementia cohort is now fully enrolled at 134 patients, at
the time of interim analysis 96 patients had evaluable safety data and 68 had
effectiveness data (at least 30 treatment days). The study endpoints included
a PBA symptom rating (Center for Neurologic Study-Lability Scale; CNS-LS; 7=no
symptoms – 35=maximum symptoms), number of weekly PBA episodes, Mini-Mental
State Examination (MMSE), quality of life (QOL; 0=no impairment-10=maximum
impairment) improvements, and Clinician and Patient Global Impression of
Change (CGI-C; PGI-C).
oAt baseline patients had a mean CNS-LS score of 20.2 and were suffering
from a median of 29 PBA episodes per week.
oAt the end of the study period, mean CNS-LS improved to 12.8 (P<0.001
compared with baseline) and the median number of PBA episodes decreased to
5 per week.
oAt the end of the treatment period, consistent improvement was observed in
other effectiveness measures
oMean QOL scores improved from 6.1 at baseline to 2.8 at endpoint
o77.8% of patients or caregivers rated themselves/the patient as being
much/very improved on the PGI-C
o79.3% of clinicians rated the patient to be much/very much improved
on the CGI-C
oMMSE mean score improved by 0.4 points at end of study from a baseline of
oAdverse Events (AE) were reported by a total of 35 (36.5%) patients (6.3%
treatment-related), most commonly headache (9.4%), urinary tract infection
(5.2%), and diarrhea (4.2%). Eleven patients had serious AEs (only one
deemed treatment-related). Thirteen patients discontinued for AEs. This
AE profile was generally consistent with that observed in other trials of
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. 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). Patients
with TBI due to a penetrating head injury are excluded. Patients are treated
with NUEDEXTA mg twice daily. The primary endpoint is change from baseline in
scores measured by the CNS-LS, a PBA rating instrument originally validated in
patients with PBA secondary to ALS and MS. 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 weekly PBA
episodes (laughing and/or crying); Mini-Mental State Examination; quality of
life; Clinician and Patient Global Impression of Change (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.
Poster Presentation Details:
Title: PRISM II: An Open-Label Study to Assess the Safety, Tolerability, and
Effectiveness of Dextromethorphan 20 mg/Quinidine 10 mg (NUEDEXTA) in
Pseudobulbar Affect (PBA) Secondary to Dementia, Stroke, or Traumatic Brain
Injury (TBI): Early Results of the Alzheimer's Disease/Dementia Cohort
Poster Number: 45758
Presentation Time: 11:45 a.m. – 2:15 p.m. CET
PBA is a neurologic condition in patients with neurologic disease and injury
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,
The CNS-LS has been validated in ALS and MS patients.
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
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 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
©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 such as continued enrollment and
data generation for the PRISM II study, and commercialization of new products
domestically and internationally, 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
+1 (949) 389-6700
Brewlife Media Contact
+1 (415) 946-1076
Avanir Pharmaceuticals, Inc.
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SOURCE Avanir Pharmaceuticals, Inc.
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