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Avanir Pharmaceuticals Announces Initiation Of Phase II Study of AVP-786 For The Adjunctive Treatment Of Major Depressive Disorder

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Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR) today announced the enrollment of the first patient into a phase II study to evaluate the efficacy, safety and tolerability of AVP-786 for the adjunctive treatment of major depressive disorder (MDD). AVP-786 is a novel investigational drug consisting of a combination of deuterium modified dextromethorphan and ultra-low dose quinidine.

"There are millions of people with MDD who remain depressed despite receiving standard antidepressant therapy," said Maurizio Fava, MD, executive vice chair, department of psychiatry at Massachusetts General Hospital, Boston. "This is an important clinical study given the properties of AVP-786 and the vast unmet need in this area."

"With a unique, multifaceted mechanism of action encompassing key neurotransmitter systems involved in regulation of mood, AVP-786 has the potential to offer a new approach for the treatment of patients with depression," said Joao Siffert, MD, chief medical officer at Avanir Pharmaceuticals.

About the MDD Study
This 10-week, multicenter, randomized, double-blind, placebo-controlled proof-of-concept phase II study will evaluate the efficacy and safety of AVP-786 in patients with major depression who have had an inadequate response to commonly prescribed antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The study is expected to enroll approximately 200 patients at approximately 30 sites in the United States. The study will utilize a sequential parallel comparison design (SPCD); a design developed ten years ago by Drs. Fava and Schoenfeld at Massachusetts General Hospital and now increasingly utilized in central nervous system (CNS) clinical trials. This study design is intended to reduce placebo response rates, a phenomenon commonly observed in depression trials. The primary efficacy measure is the Montgomery-Asberg Depression Rating Scale (MADRS) total score, a standard clinical measure of depression. Secondary outcome measures include assessments of disease severity, activities of daily living, and quality of life. Pharmacokinetics and standard safety assessments will also be conducted.

Update on the Agitation in Alzheimer's Disease Patients Study
The company expects to announce top-line results from the Agitation in Alzheimer's disease study in late September/early October 2014. The objectives of this proof of concept study are to evaluate the safety, tolerability, and efficacy of AVP-923 for the treatment of agitation in Alzheimer's patients. The trial is 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 five, 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 (full analysis population) and change from week 5 to week 10 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 will also be conducted.

About Major Depressive Disorder
Major depressive disorder (MDD) is a condition in which patients exhibit depressive symptoms, such as a depressed mood or a loss of interest or pleasure in daily activities consistently for at least a two-week period, and demonstrate impaired social, occupational, educational or other important functioning. An estimated 16 million people in the U.S. suffer from MDD in a given year. As many as two-thirds of patients who are diagnosed with MDD do not experience adequate improvement with initial antidepressant therapy.

About AVP-786
AVP-786, the company's next-generation compound, is a novel investigational drug product consisting of a combination of deuterium modified dextromethorphan (an uncompetitive NMDA receptor antagonist, sigma-1 receptor agonist and inhibitor of the serotonin transporter (SERT) and norepinephrine (NET) transporter) and ultra-low dose quinidine (a CYP2D6 enzyme inhibitor). Incorporation of deuterium into specific positions of the dextromethorphan molecule strengthens the chemical bonds and reduces susceptibility to enzyme cleavage and first pass metabolism, but without altering its pharmacology. By having a lower metabolism rate, deuterium modified DM in AVP-786 requires a substantially lower level of the metabolic inhibitor quinidine in the formulation. This may result in a reduced potential for drug interactions, while maintaining therapeutic efficacy. AVP-786 is an investigational drug not approved by the FDA.

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 being studied in several ongoing company sponsored Phase II clinical trials including agitation in Alzheimer's disease, levodopa-induced dyskinesia in Parkinson's disease, and multiple investigator initiated studies. AVP-923 is an investigational drug not approved by the FDA.

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