The US Food and Drug Administration (FDA) has accepted Avanir Pharmaceuticals, Inc.'s Investigational New Drug (IND) application for a phase II study assessing the safety and efficacy of AVP-786, Avanir's next generation compound. The company plans to initiate this study evaluating AVP-786 for the adjunctive treatment of major depressive disorder (MDD) during the third calendar quarter of 2014.

"The endorsement of this phase II study by the division of Psychiatry Products at the FDA lends support for the expedited development path for AVP-786 and is allowing us to reference the extensive data generated during AVP-923 development programmes. This is an important moment for the company, as this will be our first clinical study evaluating AVP-786 in patients," said Joao Siffert, MD, chief medical officer at Avanir Pharmaceuticals. "There are millions of patients with MDD who do not respond adequately to existing therapies.  With a mechanism of action addressing multiple neurotransmitter systems involved in depression, AVP-786, if approved, could offer a potential new treatment option for these patients. We look forward to initiating our clinical research programme in the coming months."

The filing of this IND represents the first step in Avanir's plan to develop AVP-786 for a broad array of neurological and psychiatric conditions.

This multicenter, randomized, double-blind, placebo-controlled proof-of-concept phase II study will evaluate the efficacy and safety of AVP-786 in patients suffering from MDD 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 in the United States. The study will utilize innovative methodologies to reduce the placebo response, which is commonly observed in depression trials. Eligible patients will be randomized to receive either AVP-786 or placebo for 10 weeks. The main efficacy measure is the Montgomery-?sberg 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.

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 16.1 million people in the US suffer from MDD in a given year, with as many as two-thirds of patients who are diagnosed with MDD do not experience adequate improvement with initial antidepressant therapy.

AVP-786, the company's next-generation AVP-923 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 decreasing the metabolism rate, AVP-786 requires a substantially lower level of the metabolic inhibitor quinidine. This may result in a reduced potential for drug interactions, while maintaining its therapeutic efficacy. AVP-786 is an investigational drug not approved by the FDA.

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.

Avanir Pharmaceuticals, Inc. is a biopharmaceutical company focused on bringing innovative medicines to patients with central nervous system disorders of high unmet medical need.