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).
- At baseline patients had a mean CNS-LS score of 20.2 and were
suffering from a median of 29 PBA episodes per week.
- At 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.
- At the end of the treatment period, consistent improvement was
observed in other effectiveness measures
- Mean QOL scores improved from 6.1 at baseline to 2.8 at
endpoint (P<0.001)
- 77.8% of patients or caregivers rated themselves/the patient as
being much/very improved on the PGI-C
- 79.3% of clinicians rated the patient to be much/very much
improved on the CGI-C
- MMSE mean score improved by 0.4 points at end of study from a
baseline of 19.0
- Adverse 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
NUEDEXTA.
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
About PBA
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, 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 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 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
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.