ORLANDO, Fla., June 25 Orexigen® Therapeutics, Inc. (Nasdaq: OREX) today announced data from the CORDiabetes trial for Contrave® (naltrexone sustained release (SR)/bupropion SR) showing that after 56 weeks of treatment, overweight or obese patients with type 2 diabetes lost significantly more weight and achieved greater improvement in glycemic control than those treated with placebo.
Over twice as many patients lost at least 5% of their body weight on Contrave versus placebo on an intent-to-treat (ITT) basis (44.5% vs. 18.9% respectively), according to the data presented today by Dr. Priscilla Hollander, M.D., Baylor Medical Center, at an oral session of the 70th Scientific Sessions of the American Diabetes Association. Importantly, Contrave-treated patients experienced clinically significant reductions in A1C. Average baseline A1C, the standard test for monitoring glycemic control, of approximately 8.0% was reduced by 0.6% for Contrave compared to 0.1% for placebo. This translated to over 44% of Contrave patients reaching the American Diabetes Association (ADA) treatment target for A1C of less than 7%. In comparison, 26% of placebo patients reached the same threshold (p<0.001).
"It is well understood that weight loss is beneficial for glycemic control and slows disease progression in patients with type 2 diabetes," said Dr. Hollander, a lead investigator on COR-Diabetes. "The COR-Diabetes study demonstrated the potential utility of Contrave for obese patients with diabetes, where weight loss and weight management, coupled with a clinically meaningful improvement in glycemic control, improves overall health."
The impact on A1C was shown to be most profound in Contrave patients who started the trial with poor glycemic control. In fact, those patients who had a starting A1C greater than 8% exhibited an A1C improvement of -1.1%, compared with -0.5% in patients on placebo (p<0.01). In addition, significantly fewer patients taking Contrave were treated with diabetes rescue medication (22.3%) compared to placebo patients (35.2%), (p<0.01).
According to the ADA, diabetes affects 24 million Americans, a number that is projected to grow to 44 million over the next 25 years, driven largely by rising rates of obesity. The cost of treating the disease is expected to triple over the same time period. Obesity is the single greatest risk factor for type 2 diabetes; approximately 85% of patients with type 2 diabetes are overweight or obese.
Improvements in Markers of Cardiometabolic Risk
Patients treated with Contrave also showed improvements in a number of other measures of cardiometabolic risk, as shown in the table below:
The most frequently observed treatment-emergent adverse events in COR-Diabetes were nausea, vomiting, constipation and dizziness. Nausea was the leading adverse event resulting in discontinuation.
"The results of the COR-Diabetes study demonstrate the important role of weight loss and weight management as a cornerstone in the treatment of obese patients with type 2 diabetes," commented Dr. Dennis Kim, Orexigen's Senior Vice President of Medical Affairs.
COR-Diabetes was a 56-week placebo-controlled, double-blind randomized trial of 505 overweight or obese patients with type 2 diabetes, whose A1C levels were between 7% and 10% (mean=8.0%), with most patients already taking multiple oral diabetes medications. Patients were randomized to receive either Contrave32 (naltrexone 32mg SR /bupropion 360mg SR) or placebo in a 2:1 ratio. Fifty-two sites in the United States participated in the study.
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. These were mostly mild to moderate in severity, transient, and typically occurred during the first weeks of treatment. Most common adverse events leading to discontinuation with Contrave were nausea, headache, dizziness and vomiting. 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 www.orexigen.com.
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 potential for, and timing of, approval for Contrave and the Company's belief that this product candidate may be an important therapeutic option in the treatment of obesity. 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.
Contrave32 Placebo Waist circumference, cm -5.0** -2.9 Triglycerides, % -11.2%** -0.8% HDL-cholesterol, mg/dL +3.0*** -0.3 LDL-cholesterol, mg/dL -1.4 0.0 Glucose, mg/dL -11.9 -4.0 Insulin, % -13.5% -10.4% HOMA-IR, % -20.6% -14.7% ---------- ----- ----- hs-CRP, % -20.9% -13.3% --------- ----- ----- All measurements were made in a fasting state. Values are change from baseline to Week 56 endpoint; ITT-LOCF population. Data are LS mean change, or LS percent change for values that were skewed at baseline. **P<0.01 vs. Placebo; ***P<0.001 vs. Placebo.
SOURCE Orexigen Therapeutics, Inc.