Long-term success seen in obesity drug

NEW ORLEANS -- The maker of an experimental obesity drug said yesterday that it intends to seek federal approval for the pill next spring after a new medical study showed that patients taking the medication lost 19 pounds on average and kept it off for two years -- longer than any diet drug now on the market.

With the United States amid an unprecedented epidemic of obesity, drug companies are in a pitched race to develop blockbuster medicines to help patients shed pounds and reduce the accompanying risk of cardiovascular disease, the nation's number one killer.

At least 10 antiobesity drugs are being tested in humans. The only two prescription drugs approved for long-term weight loss typically help patients trim 15 pounds or less, and one, orlistat, can cause severe indigestion.

In tests of a new drug called rimonabant, however, Columbia University researchers found that patients lost 5 percent to 10 percent of their weight and kept it off as long as they continued taking the drug. In addition to losing weight, the researchers reported, the patients also registered decreases in triglycerides, dangerous fats in the blood that increase the risk of heart disease, and improved their levels of HDL, the good form of cholesterol. The findings were reported at the American Heart Association's annual conference.

Cardiology and nutrition specialists attending the nation's premier gathering of heart doctors said the once-a-day drug would offer patients struggling to lose weight another important tool. But they also cautioned against overselling its promise: Most of the patients who took the drug in the study remained overweight at the end of the study period.

"None of these drugs in development are going to be the magic bullet," said Dr. Ernst J. Schaefer, a Tufts University nutrition researcher. "In a 300-pound person who loses 10 percent, that person still weighs 270 pounds."

Other doctors said they worried the drug, if approved, will become yet another pill-for-life in the increasingly bulging medicine cabinets of Americans.

Dr. Sidney Smith of the University of North Carolina said he would prefer that patients take weight-lowering drugs for short periods of time. "It is a bit like a jump start -- they're off," Smith said.

Rimonabant, which will be marketed as Acomplia if it wins the blessing of the US Food and Drug Administration, is in a class of emerging drugs that aim to regulate biochemical processes that have been implicated in weight gain, as well as tobacco use.

The drugs partly target fat cells, which scientists now understand are not just inactive globs. They send out chemical signals to the brain that can spur humans to overeat, and the drug blocks these chemicals from reaching receptors in the brain.

"This changes the way the fat talks to the brain to help you stop eating," said Dr. Douglas Greene, vice president of corporate medical and regulatory affairs at Sanofi-Aventis, maker of the drug.

The pill also resets the gauge in the brain that regulates the sense of being satiated, telling patients who take the drug that they're full faster.

The drug has undergone testing before, but the data released yesterday represented the longest period of study of the drug in the United States and Canada, and jibed with a two-year study of rimonabant by European researchers. The rimonabant trial included four women for every man, an imbalance common in obesity research.

When the participants began the study, they had an average waistline of 42 inches. Obesity researchers at the heart conference said that waist size is emerging as an increasingly important predictor of heart disease, potentially proving more reliable than the body mass index.

Participants who took the 20-milligram dose for two years shed 3.1 inches from their waist, compared with a 1.9-inch loss for those on the 5-milligram pill, and 1.5 inches for those receiving the placebo. At the start of the study, all the participants had been encouraged to reduce daily calories by 600. HDL cholesterol increased by nearly 25 percent in participants taking the strongest dose of the drug, substantially more than others in the study. And dieters taking the 20-milligram pill were significantly more likely to have a reduction in triglycerides, registering a 10 percent drop.

Because the drug works on parts of the brain involved with regulating pleasure, researchers were particularly attentive to side effects. Participants in relatively small numbers reported anxiety, depression, and nausea, but scientists found that the level of those complaints was nearly identical whether people were taking the medication or a dummy pill.

Dr. Robert H. Eckel, president-elect of the American Heart Association, described the research as "very robust and conclusive," and said that it was particularly heartening given that other approaches have not succeeded in helping patients maintain weight loss for longer than a few months or a year.

Greene, the Sanofi-Aventis executive, said the company expects to have completed compiling data from four different trials of rimonabant by the end of the year and will seek FDA approval in the spring.

Stephen Smith can be reached at stsmith@globe.com.