Avanir Pharmaceuticals Announces Presentation of Positive Early Results from PRISM II Study

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.

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+1 (949) 389-6700

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SOURCE Avanir Pharmaceuticals, Inc.