With a novel approach to obesity, Sanofi's Acomplia (rimonabant), now on indefinite hold in the U.S. market, perhaps the next great diet drug hope will be a promising combination of two old drugs which is now enrolling patients in two Phase III multicenter trials.

Named Contrave, the drug developed by Orexigen Therapeutics of San Diego is a combination of naltrexone SR (used to treat opiod addiction and alcoholism) and bupropion SR (used to treat depression and nicotine addiction).

Since both drugs were approved separately many years ago by the FDA, the approval process for Contrave -- if it proves successful in the 56-week phase III trials -- may prove smoother than for a totally new drug.

According to results of a 24-week Phase IIb trial, Contrave helped patients lose a "significant" amount of weight -- an average of 7% of body weight compared to 1% for patients on placebo -- while also reducing visceral fat, which is found inside the abdominal cavity and is associated with increased risk of heart disease and Type II diabetes.

Contrave is designed to act on neurons in the brain. While buproprion blocks appetite and other cravings, it also releases brain chemicals that put a brake on that effect. Naltrexone blocks the brake, allowing longer appetite suppression.

In data presented at the just concluded American Diabetes Association scientific meeting, researchers said 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.

Dr. Frank Greenway, principal Investigator of the study and Professor and Chief of the outpatient department at the Pennington Biomedical Research Center in Baton Rouge, said:

"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."

An additional encouraging finding reported was 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.

"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," said Dr. Gary Tollefson, Orexigen President and CEO.