1. Poster P01.090: Involuntary Emotional Expression Disorder (IEED) Prevalence and Treatment 2. Poster P01.015: Long-Term Safety of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Involuntary Emotional Expression Disorder (IEED) 3. Poster P01.016: Competitive Binding of Dextromethorphan to Selective Brain Receptor Sites
Walter Bradley, DM, FRCP, Professor and Chairman Emeritus, Department of Neurology at the University of Miami School of Medicine presented poster P01.090 "Involuntary Emotional Expression Disorder (IEED) Prevalence and Treatment." In this study a representative sample of 2318 patients in the U.S. with neurologic diseases or injuries known to cause IEED, or their caregivers, were surveyed to determine the prevalence of IEED symptoms. The results indicate that at least 1.8 million neurologic patients in the U.S. suffer from frequent and intense episodes of uncontrollable crying or laughing. In addition, the data indicate that up to 7 million neurologic patients suffer some degree of impairment caused by uncontrollable laughing or crying. Fifty nine percent of patients with IEED symptoms had discussed their symptoms with their physician and less than half received any diagnosis or treatment. The authors concluded that the prevalence of IEED in the U.S. appears to be greater than previously estimated in the medical literature and that education is needed to improve diagnosis and treatment. These data were deemed especially n oteworthy by the meeting organizers and selected for presentation at the AAN Scientific Topics Highlights session on Thursday, May 3, 2007.
Zenvia investigator Daniel Wynn, MD, ABSM, Co-Director of the Clinical Research Consultants in Neurology MS Center in Northbrook, IL, presented poster P01.015 "Long-Term Safety of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Involuntary Emotional Expression Disorder (IEED)." Data were presented from patients with IEED, secondary to various neurologic diseases or injuries, treated with Zenvia for 52 weeks or longer. Results indicated that adverse events were generally mild to moderate in nature with decreasing frequency after the first week of therapy; no differences in adverse event profile based on age, sex, race or underlying neurologic disease; no treatment-related serious adverse events; and no clinically meaningful effects on cardiac repolarization or any electrocardiogram variables.
In this open-label, multi-center study, 506 IEED patients with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's dementia, Parkinson's disease, or injuries such as stroke and traumatic brain injury, were enrolled to evaluate long-term safety and tolerability with 321 patients completing more than six months of treatment. Eighty-six percent of the 234 patients who completed one year of therapy chose to continue in the optional extension phase of the study. The median compliance rate with Zenvia therapy was 97.1%.
Linda Werling, Ph.D., Director, Institute for Biomedical Sciences, George Washington University Medical Center, presented poster P01.016 "Competitive Binding of Dextromethorphan to Selective Brain Receptor Sites." This study evaluated radioligand competitive binding for memantine, amitriptyline, fluoxetine, dextrorphan and dextromethorphan, the therapeutically active ingredient in Zenvia, to determine the binding affinities for each drug to 26 different target receptor binding sites in the brain. Of the 26 potential target sites screened, dextromethorphan bound to the fewest suggesting a lower risk for side effects than the other drugs tested. The authors concluded that treatment effects with dextromethorphan in Involuntary Emotional Expression Disorder (IEED) may be related to the selectivity and affinity of dextromethorphan at Sigma1 receptor sites concentrated in the brainstem and cerebellum.
All three studies were sponsored by the Company.
Zenvia is a combination of two well-characterized compounds, the therapeutically active ingredient dextromethorphan, and the enzyme inhibitor quinidine, which serves to increase the bioavailability of dextromethorphan. The first-in-class drug candidate is believed to help regulate excitatory neurotransmission in two ways, through pre-synaptic inhibition of glutamate release via sigma-1 receptor agonist activity, and through postsynaptic glutamate response modulation via uncompetitive, low-affinity NMDA antagonist activity. Zenvia is currently in development for the treatment of Involuntary Emotional Expression Disorder (IEED) and diabetic peripheral neuropathic pain.
In October 2006, the Company received an approvable letter for the treatment of Zenvia in IEED. To address safety concerns raised in the FDA's approvable letter for Zenvia for the treatment of IEED, the company intends to initiate a confirmatory phase III study with a new lower quinidine dose formulation of Zenvia. In April 2007 Avanir completed the first of two planned phase III studies in diabetic peripheral neuropathic pain where all primary endpoints were successfully met. The Company is considering whether it would be necessary or advisable to study a similar lower dose of quinidine in the second phase III trial being planned for diabetic peripheral neuropathic pain.
Avanir Pharmaceuticals is focused on developing, acquiring and commercializing novel therapeutic products for the treatment of chronic diseases. Avanir's products and product candidates address therapeutic markets that include the central nervous system, cardiovascular disorders, inflammation and infectious diseases. Avanir currently markets FazaClo(R), the only orally-disintegrating formulation of clozapine for the management of severely ill schizophrenic patients who fail to respond adequately to standard schizophrenic drug treatments. FazaClo is also indicated for reducing the risk of suicidal behavior in patients with schizophrenic or schizoaffective disorder. For full prescribing information and important safety information regarding FazaClo, please visit www.fazaclo.com. Avanir's lead product candidate for the treatment of involuntary emotional expression disorder (IEED), Zenvia(TM), is the subject of an approvable letter from the FDA. Additionally, Avanir recently completed a Phase III clinical trial with Zenvia in patients with diabetic peripheral neuropathic pain where all primary endpoints were met. Avanir has an ongoing development program with Novartis International Pharmaceutical Ltd. for the treatment of inflammatory disease. The Company's first commercialized product, Abreva(R), is marketed in North America by GlaxoSmithKline Consumer Healthcare and is the leading over-the-counter product for the treatment of cold sores. Further information about Avanir can be found at www.avanir.com.
Forward Looking Statement
Statements in this press release that are not historical facts, including statements that are preceded by, followed by, or that include such words as "estimate," "intend," "anticipate," "believe," "plan," "goal," "expect," or similar statements, are forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from the future results expressed or implied by such statements. There can be no assurance that the Co mpany will receive FDA regulatory approval for Zenvia or that the additional development work for Zenvia will be completed in the time periods that are anticipated. Final review decisions made by the FDA and other regulatory agencies concerning are often unpredictable and outside the influence and control of the Company. Risks and uncertainties also include the risks set forth in Avanir's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and from time-to-time in other publicly available information regarding the Company. Copies of this information are available from Avanir upon request. Avanir disclaims any intent to update these forward-looking statements.
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