AVANIR COMPANY STATEMENT “PBA is a neurological condition that affects up to an estimated 2 million Americans, but can be misunderstood by patients and their families. When someone with PBA has an intense laughing or crying episode, he or she can feel powerless, embarrassed, or discomforted. PBA occurs in people who already have a neurological condition, such as ALS, MS, stroke, Alzheimer’s disease, other dementias, or traumatic brain injury. Because neurological disorders commonly occur in residents of long-term care facilities, treatment with NUEDEXTA® can be appropriate for residents in these facilities who also have PBA. Prior to NUEDEXTA, there were no FDA-approved medications for the treatment of PBA. Obtaining FDA approval is an intentionally rigorous process designed to ensure a medicine’s safety and efficacy. The FDA approves about 1 in 10 New Drug Applications. Avanir spent more than 10 years and hundreds of millions of dollars to conduct extensive clinical studies and bring NUEDEXTA to market. NUEDEXTA has a wellcharacterized safety profile in patient populations with neurological disease or injury. Our goal is to give doctors truthful, accurate and balanced information so they can decide on the proper treatment for their patients. We are committed to providing information on PBA and NUEDEXTA in ways that are consistent with the law and the values and expectations of the doctors and patients we serve. Our promotional materials are subject to internal review and submission to FDA and Avanir’s Comprehensive Compliance Program, Code of Business Conduct and Ethics, and compliance policies reflect our commitment to an ethical culture. At Avanir Pharmaceuticals, we are proud to be a pioneer and dedicated to serving patients by developing innovative treatments to address unmet medical needs of people with CNS disorders, and are heavily investing in R&D to achieve this goal. We are committed to raising public awareness of little known disorders such as PBA and developing innovative, first-of-their-kind treatments. Our research and development activities are focused on important unmet needs in the areas of Alzheimer’s disease, Schizophrenia, Traumatic Brain Injury, and Migraine.” AVANIR STATEMENT ON PBA AND NUEDEXTA® NUEDEXTA® is the first and only medicine FDA has approved as safe and effective for treating Pseudobulbar Affect (PBA). PBA is a medical condition that causes involuntary, sudden, and frequent episodes of crying and/or laughing in people living with certain neurologic conditions or brain injury. PBA episodes are typically exaggerated or don’t match how the person feels. When someone with PBA has an intense laughing or crying episode, he or she can feel powerless, embarrassed, or discomforted— particularly when these outbursts come at the wrong time or are misconstrued by others. PBA can impact one’s ability to work, impair social function, and diminish quality of life for people already facing challenges from other neurological disorders.i It is estimated that up to 2 million Americans suffer from PBA.ii It occurs in people who already have a neurological condition, such as ALS, MS, stroke, Alzheimer’s disease, other dementias, or traumatic brain injury. These conditions are thought to damage brain pathways regulating emotional expression. In a registry of 5,290 patients with diverse underlying neurological conditions, over a third had screening tool scores suggesting PBA symptoms.iii Because Alzheimer’s, Parkinson’s and other neurological disorders commonly occur in residents of long-term care facilities, treatment with NUEDEXTA can be appropriate for residents in these facilities who also have PBA.iv Prior to NUEDEXTA, there were no FDA-approved medications for the treatment of PBA.v Obtaining FDA approval is an intentionally rigorous process designed to ensure a medicine’s safety and efficacy.vi FDA approves about 1 in 10 New Drug Applications.vii Discovering treatments related to the central nervous system is a particularly complex, intensive process, with no guarantees of success. From 2013-2015, medications to treat central nervous system diseases had the second highest failure rate in phase II and phase III clinical trials.viii Avanir spent more than 10 years and hundreds of millions of dollars to conduct extensive clinical studies and bring NUEDEXTA to market.ix FDA approved NUEDEXTA after careful review of the safety and efficacy, including detailed prescribing information for the use of the drug. The prescribing information is available at https://www.nuedexta.com/sites/default/files/pdfs/Prescribing_Information.pdf. NUEDEXTA is comprised of two drugs: dextromethorphan and quinidine. While these are individuallyknown ingredients used for the treatment of other medical conditions, only the specific fixed-dose combination developed by Avanir has been approved by FDA for the treatment of PBA. In Avanir’s clinical development program, the optimal dosage of these ingredients was determined in order to achieve clinical benefit for patients, while also carefully maintaining the safety profile of the medicine. In the pivotal NUEDEXTA clinical trial, which looked at patients suffering from ALS or MS, weekly rates of PBA episodes showed decreases at all time points assessed. Also, the reduction in the daily PBA episode rate was greater in each of the NUEDEXTA groups versus the placebo group.x And in a study assessing effectiveness of NUEDEXTA for treatment of PBA secondary to other neurological conditions such as dementia, stroke, and traumatic brain injury, the magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS.xi Unfortunately, PBA can be misunderstood by patients and their families, and misdiagnosed by physicians. Avanir is raising awareness among doctor and patient communities about PBA and its symptoms. NUEDEXTA has a well-characterized safety profile in patient populations with neurological disease or injuryxii and our goal is to give doctors truthful, accurate and balanced information so they can decide on patient-care plans that reflect their medical knowledge and experiences. We also are committed to providing information on PBA and NUEDEXTA in ways that are consistent with the law, and the values and expectations of the doctors and patients we serve. Avanir’s Comprehensive Compliance Program, Code of Business Conduct and Ethics, and compliance policies reflect our commitment to an ethical culture. Our promotional materials are subject to internal review and submission to FDA. At Avanir Pharmaceuticals, we are proud to be a pioneer and dedicated to serving patients by developing innovative treatments to address unmet medical needs of people with CNS disorders, and are heavily investing in R&D to achieve this goal. We are committed to raising public awareness of little known disorders such as PBA and developing innovative, first-of-their-kind treatments. Our research and development activities are focused on important unmet needs in the areas of Alzheimer’s disease, Schizophrenia, Traumatic Brain Injury, and Migraine. Arciniegas D.B., et al. The differential diagnosis of pseudobulbar affect: distinguishing PBA among disorders of mood and affect. CNS Spectr. (2005)10(5 Suppl):1- 16; Colamonico J., et al. Pseudobulbar affect: burden of illness in the USA. Adv. Ther. (2012) 29(9):775-798; Shaibani A.T., et al. Laughter and crying in neurologic disorders. Neuropsychiatry Neuropsychol Behav Neurol. (1994) 7(4):243-250; Brooks B.R., et al. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PloS one. (2013) 8(8):e72232; Work S.S., et al. Pseudobulbar affect: an under-recognized and under-treated neurological disorder. Adv. Ther. (2011) 28(7):586601. i Work, et al., supra (U.S. PBA prevalence, across different neurologic conditions, was estimated in a Harris Poll Online (HPOL) survey completed for or by 2318 patients diagnosed with any of six neurological conditions commonly associated with PBA. Mean prevalence of PBA across all six conditions was 10.1% based on a Pathological Laughing and Crying Scale (PLACS), score ≥13; 9.4%, based on a Center for Neurologic Study Lability Scale score ≥21, and 37.5% based on a lower CNS-LS ≥13 threshold.); Brooks B.R., et al., supra. ii Brooks B.R., et al., supra. (This data is based on a CNS-LS, which is a screening tool that measures PBA symptom frequency and severity, and has been validated in PBA patients with ALS and MS. Presence of PBA symptoms was defined as a CNS-LS score ≥13 but does not confer a diagnosis, which requires confirmation by a physician.) iii Foley, et al., Int J Geriatric Psychiatry (2016) 31:694-701. iv v Schiffer, et al. Affect Including a Novel and Potential Therapy. J Neuropsychiatry Clin Neurosci (2005)17:4; Hammond, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurology (2016) 16:89. “Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA. The drugs that do must undergo the agency's rigorous evaluation process, which scrutinizes everything about the drug--from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured.” (The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective. Available at: https://www.fda.gov/drugs/resourcesforyou/consumers/ucm143534.htm [last accessed on 6/28/17].) vi vii Thomas, et al., Clinical Development Success Rates 2006-2015. BIO Industry Analysis (June 2016). viii Harrison, R.K., Phase II and Phase III Failures: 2013-2015. Nature Reviews Drug Discovery (2016) 15:817-818, Figure 1. ix Avanir data on file. x Pioro, et al. Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect. Ann Neurol. (Nov. 2010) 68(5):693-702. xi Hammond, et al., supra. xii NUEDEXTA Prescribing Information; Hammond, et al., supra.