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--Data to be Presented Today at the American Diabetes Association 67th

Scientific Sessions in Chicago--

    SAN DIEGO and CHICAGO, June 23 /PRNewswire-FirstCall/ -- Orexigen(TM)
 Therapeutics, Inc. (Nasdaq:   OREX), a biopharmaceutical company focused on
 the treatment of central nervous system disorders with an initial focus on
 obesity, today announced that data from a sub-study of its Phase IIb multi-
 center clinical trial of Contrave(TM) demonstrated robust improvements in
 both visceral fat and insulin resistance.
     Contrave is a proprietary fixed dose combination of bupropion SR
 (sustained release) and Orexigen's novel formulation of naltrexone SR in a
 single tri-layer tablet. Contrave is designed to act on neurons in the
 brain with the goal of achieving appetite suppression, decreased food
 craving, and sustained weight loss.
     Across the three Contrave arms, the mean reduction in visceral fat
 ranged from 13.7% to 16.7% after 24 weeks of treatment compared to a mean
 4.6% reduction among the placebo group. Moreover, the effect of Contrave
 was substantially larger than that seen with either of Contrave's
 individual components when given alone. Visceral fat is located inside the
 abdominal cavity and surrounds vital organs such as the liver. Visceral fat
 accumulation, as opposed to subcutaneous fat which is found just underneath
 the skin, is associated with increased risk of heart disease and Type II
 diabetes.
     Additional findings from this sub-study of 107 obese subjects revealed
 that Contrave improved measures of insulin resistance and demonstrated a
 positive impact on a number of other risk factors including triglycerides,
 cholesterol, and blood sugar. Together, such improvements hold potential
 for longer term health benefits.
     "These clinical findings suggest the weight loss associated with
 Contrave also included a substantive loss in visceral fat. This is
 important for both patients and physicians because of the well-recognized
 link between visceral fat, diabetes and heart disease," said Gary
 Tollefson, M.D., Ph.D., Orexigen President and CEO. "We believe that
 Contrave may represent an important new weapon in the treatment of obesity,
 not only for the weight loss it appears to produce, but also for its
 potential impact on the behavioral and metabolic sequelae associated with
 obesity."
     "The effect of Contrave on markers of insulin resistance is a novel
 observation that has potential to demonstrate a greater level of
 pharmacological synergy than had been anticipated," said Frank Greenway,
 M.D., Principal Investigator of the study and Professor and Chief of the
 outpatient department at the Pennington Biomedical Research Center in Baton
 Rouge. "In this study, the effect of Contrave on insulin resistance and
 other metabolic factors was superior to what was seen with placebo,
 bupropion, or naltrexone alone."
     Contrave is now being studied in two separate multi-center Phase III
 studies, one of which is designed to assess its safety and efficacy in
 obese subjects with Type II diabetes.
     Data on the effect of Contrave on visceral fat and insulin resistance
 will be presented at the ADA 67th Scientific Sessions on Saturday, June
 23rd, 6:00- 7:15pm and Monday, June 25th, 12:00-2:00pm in Chicago (IL).
 Contrave data can be found in category 20B, poster number 45LB entitled,
 "Weight Loss with Bupropion and Naltrexone Improves Markers of
 Insulin-Resistance."
     About Orexigen Therapeutics
     Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on
 the development of pharmaceutical product candidates for the treatment of
 central nervous system disorders, with an initial focus on obesity.
 Orexigen's lead combination product candidates targeted for obesity are
 Contrave(TM), which is in Phase III clinical trials, and Empatic(TM)
 (formerly Excalia(TM)), which is in a Phase IIb clinical trial. Both
 product candidates take advantage of the Company's understanding of how the
 brain appears to regulate appetite and energy expenditure, as well as the
 mechanisms that come into play to limit weight loss over time. Each product
 candidate is designed to act on a specific group of neurons in the central
 nervous system with the goal of achieving appetite suppression and
 sustained weight loss. Further information about the Company can be found
 at http://www.Orexigen.com.
     Forward Looking Statements
     Orexigen cautions you that statements included in this press release
 that are not a description of historical facts are forward-looking
 statements. The inclusion of forward-looking statements should not be
 regarded as a representation by Orexigen that any of its plans will be
 achieved. For example, statements regarding the potential of Contrave(TM)
 to produce weight loss and achieve longer term health benefits for
 metabolic syndromes associated with obesity such as heart disease and
 diabetes are forward looking statements. Actual results may differ
 materially from those set forth in this release due to the risks and
 uncertainties inherent in Orexigen's business, including, without
 limitation: the results of this Phase IIb clinical trial and earlier
 clinical trials may not be predictive of future results; Orexigen's pending
 clinical trials may not proceed in the timeframes or in the manner Orexigen
 expects or at all; unexpected findings relating to Contrave(TM) or
 Empatic(TM) that could delay or prevent regulatory filings, approval or
 commercialization, or that could result in recalls or product liability
 claims; Orexigen and its licensors may not be able to obtain, maintain and
 successfully enforce adequate patent and other intellectual property
 protection of its product candidates; and other risks detailed in
 Orexigen's public filings with the Securities and Exchange Commission. You
 are cautioned not to place undue reliance on these forward-looking
 statements, which speak only as of the date hereof. All forward-looking
 statements are qualified in their entirety by this cautionary statement and
 Orexigen undertakes no obligation to revise or update this news release to
 reflect events or circumstances after the date hereof. This caution is made
 under the safe harbor provisions of Section 21E of the Private Securities
 Litigation Reform Act of 1995.
     CONTACTS:
 
     OREXIGEN              MEDIA                   INVESTORS
     Graham Cooper         Stephen Gendel          Jason Spark
     858 436-8600          212 918-4650            619 849-6005
 
 

SOURCE Orexigen Therapeutics, Inc.