Avanir Pharmaceuticals Announces Data Presentations at the American Neurological Association's (ANA) 2014 Annual Meeting Including Results from the Phase II Trial for Treatment of Agitation in Patients with Alzheimer's Disease

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

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Avanir Pharmaceuticals, Inc.

 

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