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OREXIGEN THERAPEUTICS, INC. filed this Form S-1/A on 04/09/2007
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attenuate, or limit the effect of, the pathways in the brain that prevent extended weight loss. Our combination approach contrasts with most currently approved weight loss drug therapies, which utilize a single active ingredient and have typically shown early weight loss followed by a plateau after several months of treatment. We believe that our approach to obesity drug development will permit a more sustained, clinically relevant pattern of weight reduction. Results from our clinical trials to date for both Contrave and Empatic have supported this hypothesis. We believe that our strategy will increase our probability of technical success while reducing both the time and cost associated with development.
In addition, we are seeking to improve the profiles of our product candidates by developing proprietary sustained release, or SR, drug delivery formulations for their constituent drugs. To date, compositions of Contrave and Empatic using these proprietary SR formulations for the constituents naltrexone and zonisamide, respectively, have demonstrated improved patient tolerability compared to those using previously approved immediate release, or IR, formulations of naltrexone and zonisamide. Because of differences in pharmacokinetics between the generically available formulations and our proprietary SR formulations, we believe we can enhance patient outcomes and our competitive position.
We will need to conduct additional clinical trials in order to provide enough evidence regarding efficacy and safety to submit a new drug application, or NDA, to the U.S. Food and Drug Administration, or FDA, for potential regulatory approval. These trials may not corroborate our earlier results. In addition, undesirable side effects of our product candidates may delay or prevent their regulatory approval.
In April 2006, we met with the FDA to discuss the remaining clinical trial requirements for submission of NDA filings for both Contrave and Empatic. Based on feedback from the FDA, we intend to conduct clinical development programs to provide active drug exposure among 1,500 patients for one year, under double-blind, placebo-controlled conditions for each product candidate. We expect to file an NDA with the FDA in the second half of 2009 for Contrave and in 2011 for Empatic, assuming that our clinical trials proceed as scheduled and are successful.
Contrave is a fixed dose combination of naltrexone SR and bupropion SR. We chose these constituents based on the results of our screening model as well as our understanding of the circuitries in the brain that regulate appetite and energy balance. In particular, naltrexone was chosen as a complement to bupropion in order to block compensating mechanisms that attempt to prevent long term, sustained weight loss. We hold the exclusive license to two issued U.S. patents covering the Contrave composition, and we have filed additional patents covering various compositions, methods of use and formulations.
Naltrexone was approved in the United States in 1984 for the treatment of opioid addiction and in 1995 for the treatment of alcoholism. Naltrexone works by blocking opioid receptors in the brain and inhibits the reinforcing aspects of addictive substances, reducing their perceived reward. It has been shown in numerous studies to negatively alter the palatability, or taste, of many foods, particularly sweets, including, for example, a study published in the October 2002 issue of Neuroscience and Biobehavioral Reviews. However, nausea is a well-known side effect associated with naltrexone that affects its tolerability. In our Contrave clinical trials to date, we have used the generic IR formulation of naltrexone. Commencing with our Phase III trials, naltrexone will be delivered in our proprietary SR formulation in order to improve its tolerability.
Bupropion was approved for marketing in the United States in 1985 for depression and in 1997 for smoking cessation. Functionally, bupropion is thought to increase the level of dopamine activity at specific receptors of the brain, which appears to lead to a reduction in appetite and increase in energy expenditure. It is currently among the most commonly prescribed anti-depressants in the United States, according to IMS Health. Bupropion has become popular in the treatment of depression not only for its clinical efficacy, but also its attractive side effect profile, including modest weight loss.