Contrave™ (Orexigen) Reports Positve 24-Week Data on Obesity Treatment

Orexigen Therapeutics announced that top-line results for the company’s lead obesity compound, Contrave™, demonstrated significant advantages in weight loss in a 24-week multicenter, placebo-controlled, Phase III trial. The trial will continue unblinded for an additional 24 weeks. Contrave is a proprietary combination of bupropion, a dopamine and norepinephrine reuptake inhibitor, with one of several different doses of naltrexone, an opioid antagonist used to treat various addictive disorders. The bupropion/naltrexone combination is based on the company’s underlying research into the brain’s regulation of appetite and energy expenditure, which suggests that combining these two central nervous system drugs may improve the ability to initiate weight loss and to continue weight loss by blocking the body’s attempts to compensate for weight loss during the treatment.

In what may become the preferred dose pairing based on performance and tolerability, patients completing the 24-week trial experienced on average an excess of 7 percent weight loss from baseline compared with approximately 1 percent weight loss from baseline on average for patients using the placebo. In addition, the Contrave combination outperformed either naltrexone or bupropion given alone, and the Contrave-associated weight loss trajectory showed no indication of reaching a plateau at the conclusion of 24 weeks of blinded therapy.

The trial involves more than 250 patients at 14 clinical sites and was blinded for the first 24 weeks. A second 24 weeks of open-label treatment is currently under way. The three doses of naltrexone were selected based on the company’s innovative use of Positron Emission Tomography imaging of the opioid receptors in the human brain. No serious adverse events attributed to Contrave were reported by the study’s investigators at any of the three dosages tested.

Endocrinology/Metabolics, Sept 2006