Sanofi's Obesity Drug May Help Smokers Quit, Sans Weight Gain
LONDON -- An experimental drug shows promise in helping people to quit smoking and avoid the weight gain that often comes with kicking the habit.
In recent clinical trials, Sanofi-Synthelabo SA's new obesity drug Rimonabant was given to 360 smokers during a four-week period. About 30% of those who took the drug abstained from lighting up during the last week of treatment, compared with 15% of those who took a placebo, a company official said. And while those in the placebo group gained an average of 2.4 pounds during the experiment, those who took Rimonabant lost an average of 2.6 pounds.
Tobacco kills about 4.2 million people every year and is the single largest preventable cause of death world-wide, according to the World Health Organization.
The potential market for effective smoking-cessation products is large. Available products -- such as nicotine patches or inhalers -- are ineffective for many people. Despite the health advantages that come from giving up cigarettes, many image-conscious smokers don't stop because they worry about weight gain. According to the U.S. Surgeon General's office, smokers who stop typically put on as much as 10 pounds.
"Our drug could be significant because it could help people stop smoking without increasing weight," said Gerard Le Fur, head of research for Sanofi.
Mr. Le Fur said the French company is starting late-stage tests, known as Phase 3 trials, for the use of Rimonabant as a smoking-cessation drug. If the tests yield good results, the company plans to apply for U.S. marketing approval in 2004.
Rimonabant was originally developed as an obesity treatment, which explains why it also appears to help cigarette quitters lose weight. In creating the drug, Sanofi scientists were inspired by the fact that when people smoke marijuana they get the "munchies" -- a strong urge to eat. The researchers figured that a compound that blocked that desire might also make a potent diet drug.
When a person smokes marijuana, the active compound in the drug enters the brain and latches onto certain receptors in the brain known as central cannabinoid receptors. These receptors are believed to play a role in controlling appetite and the phenomena of craving and dependence -- on nicotine or alcohol, for example. Rimonabant is a synthetic compound that essentially blocks the receptors. As a result, the brain temporarily stops sending "feed me" signals.
In the case of a smoker, Rimonabant's blocking of the receptors also appears to influence the brain's "reward system." This system typically reinforces healthy behavior, such as eating when hungry. It does this by releasing a pleasure-giving chemical called dopamine. However, potentially harmful and addictive substances like nicotine or alcohol also make use of the reward system. By capping the receptors, Rimonabant appears to block the release of dopamine in the brain of a smoker, and thereby breaking the cycle of craving that can occur.
Sanofi plans to seek U.S. regulatory approval in late 2004 to market the drug for both obesity and smoking cessation. "It all depends on whether we get positive results" in Phase 3 trials for both indications, said Mr. Le Fur. He added that the company has already had some success in using Rimonabant to reduce alcohol consumption in rats, and plans similar tests on people soon.