Orexigen® Therapeutics COR-BMOD Study Published in the Journal Obesity

SAN DIEGO, Aug. 3 /PRNewswire-FirstCall/ -- Orexigen® Therapeutics, Inc. (Nasdaq: OREX) announced the online publication of results from its COR-BMOD trial of Contrave® (naltrexone SR/bupropion SR) in the journal Obesity. The COR-BMOD trial evaluated intensive behavior modification (BMOD) plus Contrave32 (32mg naltrexone sustained release (SR)/360mg bupropion SR) compared to BMOD plus placebo, in 793 overweight or obese patients. The addition of Contrave to BMOD delivered significant incremental weight loss and improvements in measures of cardiometabolic risk.  Results showed that patients taking Contrave lost 9.3% of their body weight compared to 5.1% for patients on placebo (p< 0.001), on an intent-to-treat basis.  For those who completed 56 weeks of treatment, patients taking Contrave plus BMOD lost 11.5% of their body weight compared to 7.3% for those taking placebo (p<0.001).

Behavior modification, including diet and exercise, has long been considered the standard of care in managing obesity.  The benefit of adding specific pharmacotherapies to a rigorous BMOD program has not been extensively evaluated.  COR-BMOD was designed to test this hypothesis by evaluating Contrave in a setting conducive to maximum weight loss in which patients used the medication as part of a broader weight-loss effort.  Participants in both groups received diet and exercise counseling during 28 small group sessions with one or two professionals, each lasting 90 minutes, over the course of the year-long trial.

"There is no magic bullet for the treatment of obesity.  For some patients, effective and sustainable treatment is going to require a multi-modal approach which may include a combination of behavior modification and pharmacotherapy," said Thomas Wadden, Ph.D., lead investigator and Professor of Psychology in Psychiatry at the University of Pennsylvania School of Medicine and Director of the Center for Weight and Eating Disorders.  "This study clearly demonstrates that when Contrave is added to a state of the art diet and exercise regimen, patients can achieve significant incremental weight loss."  

Results showed that the addition of Contrave to intensive behavior modification was also associated with statistically significant greater improvements in markers of cardiometabolic risk, including waist circumference, triglycerides, high density lipoprotein (HDL) cholesterol and fasting insulin.  The most common adverse events included nausea, headache, constipation and dizziness.  Observed adverse events were, in general, consistent with the other studies within the COR program and with the safety profile of the constituent components.

"Medication alone may not be the answer for the majority of obese patients, so it's important that we understand the benefits of a multi-modal weight loss program," said Michael Narachi, CEO of Orexigen.  "The results from this study reinforce our belief that a weight management strategy, addressing both the biological and behavioral drivers of obesity, can be successful."

Study Design

COR-BMOD was a 56-week placebo-controlled, double-blind, randomized trial that enrolled overweight and obese adults.  A total of 793 patients were randomized to receive either Contrave32 + BMOD or placebo + BMOD in a 3:1 ratio.  Nine sites in the United States participated in the study.

About Contrave

Contrave is an investigational combination therapy believed to address both physiological and behavioral drivers of obesity.  The two components of this combination therapy act in a complementary manner in the central nervous system.  The central pathways targeted by this treatment are involved in controlling the balance of food intake and metabolism, and regulating reward-based eating behavior.  In clinical trials, Contrave was shown to help obese patients initiate and sustain significant weight loss, improve important markers of cardiometabolic risk and increase ability to control eating.  The U.S. Food and Drug Administration (FDA) has tentatively scheduled a Division of Metabolic and Endocrine Drug Products Advisory Committee meeting on December 7, 2010 and the Prescription Drug User Fee Act (PDUFA) action date has been set for January 31, 2011.

About the Contrave Clinical Development Program

All four trials in the COR Phase 3 program (COR-I, COR-II, COR-BMOD and COR-Diabetes) were randomized, double-blind, placebo-controlled trials.  The co-primary endpoints were the proportion of patients achieving at least 5% weight loss and percent change in body weight compared to placebo. Secondary endpoints included multiple measures of cardiometabolic risk, quality of life, control of eating, and glycemic control.  Contrave was generally well tolerated.  The safety and tolerability profile of Contrave in the clinical development program was consistent with the safety profile of the constituent components, which have been in use for other indications for over 20 years.  The most frequent treatment-emergent adverse events in patients treated with Contrave were nausea, constipation, headache, vomiting and dizziness.  Treatment with Contrave was not associated with increases in adverse event reports of depression or suicidal ideation compared to placebo.  Mean blood pressure with Contrave was generally unchanged from baseline to endpoint.  Placebo patients experienced decreases in blood pressure from baseline to endpoint of approximately 2mmHg.  Greater weight loss correlated with greater reductions in blood pressure in both Contrave and placebo patients, suggesting that the expected relationship between weight loss and blood pressure was maintained.  Importantly, normal circadian blood pressure patterns were preserved with Contrave.  There was an increase in pulse of about one beat per minute in patients taking Contrave.  Serious events were reported infrequently and included events of cholecystitis (Contrave 0.2%, PBO <0.1%), seizure (<0.1%, 0%) and major cardiovascular events (<0.1%, <0.1%).

About Orexigen Therapeutics

Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the treatment of obesity.  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. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward-looking statements. These statements are based on the Company's current beliefs and expectations. These forward-looking statements include statements regarding the anticipated action date for the FDA to complete its review of the Contrave NDA, the potential for, and timing of, approval for Contrave and the Company's belief that a weight management strategy, addressing both the biological and behavioral drivers of obesity, can be successful and may offer patients lasting success. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in the Orexigen business, including, without limitation: the uncertainty of the FDA approval process and other regulatory requirements; the therapeutic and commercial value of Contrave; reliance on third parties to assist with the development of Contrave; the potential for adverse safety findings relating to Contrave; and other risks described in the Company's 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, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in the Company's Quarterly Report on Form 10-Q, which was filed with the Securities Exchange Commission on May 10, 2010 and is available from the SEC's website (www.sec.gov) and on our website (www.orexigen.com) under the heading "Investor Relations". All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

SOURCE Orexigen Therapeutics, Inc.