Orexigen presents findings on obesity drug candidates

Orexigen Therapeutics, Inc., a biopharmaceutical company focused on the treatment of central nervous system (CNS) disorders including obesity, has presented the results of a preclinical study that further supports the Company's understanding of an aspect of the mechanism of action of Contrave, one of its two late-stage obesity drug candidates.

The findings showed:

• The combination of bupropion and naltrexone resulted in a 94% reduction of food intake in obese mice, greater than either drug alone;
• The drugs act in a part of the brain where food reward pathways are located
• The combination directly increased firing of neurons associated with reduction in food intake and satiety.

The data were disseminated in a poster presentation* at The Obesity Society's Annual Scientific Meeting (NAASO) being held in New Orleans, October 20-24, 2007. “We originally theorized that the combination of bupropion and naltrexone, the components of Contrave, would stimulate proopiomelanocortin (POMC) neuronal firing which would lead to sustained weight loss. These new findings indicate that Contrave may also modulate food cravings through its effect on reward pathways,” said Orexigen founder and Chief Scientific Officer, Michael Cowley, Ph.D. “We believe this aspect of Contrave's mechanism of action may have the potential to differentiate it from other pharmaceutical therapies available or in development for the treatment of obesity.”

One study examined the effects of bupropion, naltrexone and the combination of bupropion plus naltrexone in both lean and obese mice. In lean mice, treatment with bupropion, naltrexone or the combination resulted in a 34%, 67% and 77% reduction of food intake, respectively. In obese mice, treatment with bupropion, naltrexone or the combination resulted in a 27%, 49% and 94% reduction of food intake, respectively. The interaction between bupropion and naltrexone appeared more potent in obese mice than in lean mice.

A separate study examined the effects of bupropion, naltrexone or the combination of bupropion plus naltrexone when they were selectively administered to the ventral tegmental area (VTA), a part of the brain that is often described as the center of “the reward pathway”. This is the region of the brain that determines whether an environmental stimulus is rewarding or aversive. The combination of bupropion plus naltrexone in the VTA caused a statistically significant, synergistic reduction of food intake suggesting a possible connection to the behavioral aspects of obesity.

Contrave employs a proprietary formulation of two CNS molecules, bupropion and naltrexone, that have been independently approved by the US Food and Drug Administration in other indications. Orexigen chose these two constituent drugs based on the results of a proprietary screening model and the Company's understanding of circuitries in the brain that regulate appetite and energy balance. The unique combination of these molecules is designed to provide more clinically meaningful weight loss for patients by both initiating weight loss and sustaining it over a longer period of time.