OREX-003
OREX-003 is the working name we have given to the olanzapine/zonisamide SR combination product candidate that we are currently developing for the mitigation of weight gain associated with antipsychotic therapy. We own or have exclusive rights to two patent applications currently pending in the United States and a number of corresponding patent applications currently pending in various foreign countries with respect to various compositions, methods of use and formulations relating to this product candidate.
The market for antipsychotic agents has grown dramatically over the last 10 years, as the second generation or “atypical” group of medications has been increasingly prescribed for schizophrenia and bipolar disorder. There are severe, chronic and often disabling disorders that affect over 8.0 million adults in the United States, according to the National Institute of Mental Health. The current group of medications has been called atypical because they are not associated with the adverse event profile of the first generation of antipsychotic agents, which have been prescribed since the 1950s. The antipsychotic drug with the highest sales over the last five years has been olanzapine, which is marketed under the brand name Zyprexa. At its peak in 2004, worldwide Zyprexa sales totaled approximately $4.4 billion, according to Eli Lilly and Company. Despite the historical commercial success of Zyprexa, new prescriptions have declined as a result of its side effects, particularly excessive weight gain and metabolic effects. The Zyprexa package insert reports that in an analysis of 13 placebo-controlled trials of olanzapine, 56% of patients gained 7% or more of baseline body weight in long-term trials. Consequently, we believe there is currently a high degree of concern about Zyprexa among patients and physicians, resulting in poor compliance and a growing reluctance to prescribe it.
Evidence that zonisamide could be an effective complement to address olanzapine-associated weight gain and related metabolic effects derives from human and animal studies. According to a study published by Wang et al in the July 2007 issue of the Journal of Psychiatric Research, zonisamide has shown potential as an effective and generally well-tolerated treatment for psychotropic-induced weight gain in bipolar disorder patients. Further evidence for the potential benefit of zonisamide use in conjunction with olanzapine derives from a preclinical animal study led by Michael A. Cowley, Ph.D., our co-founder and Chief Scientific Officer, in which zonisamide attenuated olanzapine-associated increase in appetite, weight gain and elevated blood glucose. The study also showed that zonisamide normalized the activation of the appetite-associated orexin circuitry in the rat brain associated with olanzapine treatment.