The pill for big ills

NEW ORLEANS -- A new pill in the final stages of testing shows promise in attacking two of humanity's biggest killers by helping people quit smoking and lose weight at the same time.

As government officials in Washington launched a campaign against obesity Tuesday, doctors at a medical conference here described the new drug as provocative and perhaps ideal for some people.

The drug, which could be available in a year or two, works by an entirely new approach -- by blocking the same primeval circuitry in the brain that gives pot-smokers the munchies.

The development could offer a well-timed one-two punch against Americans' gravest health concerns. Smoking is the country's top killer, accounting for 435,000 deaths in 2000. The combination of poor diet, obesity and physical inactivity are right behind, with 400,000 deaths.

Doctors who heard data on the new pill said that while better living habits should be the foundation of good health, a new pill could be an important boost for those who cannot accomplish it through willpower alone.

"We tell people to diet and exercise, and that advice doesn't seem to be very effective," said Dr. Raymond Gibbons of the Mayo Clinic, who called the latest results "very provocative."

Two reports on the drug, called rimonabant, were released in New Orleans at a meeting of the American College of Cardiology. The research was financed by the drug's developer, the French firm Sanofi-Synthelabo, which plans to seek U.S. approval to sell it under the brand Acomplia after more studies are finished next year.

One study found the drug helped people drop 20 pounds in a year, while the other concluded it doubles smokers' success at quitting, at least in the short run. Doctors said the drug is likely to be marketed both for dieting and smoking cessation, but it is likely to be especially appealing to people beset by both problems.

Doctors say the drug is also noteworthy because it takes a fresh approach to helping people overcome their yen for food and tobacco. It is the first of a class of medicines that block the so-called endocannabinoid system.

Marijuana makes people ravenous by stimulating this circuitry. The same biological machinery serves crucial everyday purposes by helping the brain regulate hunger and probably other urges, including alcohol craving.

Overeating and smoking can overstimulate this system, which in turn propels them to eat and smoke still more. By temporarily blocking the body's ability to receive these signals, experts believe they can return the system's working to normal.

In the larger of the two studies, Dr. Jean-Pierre Despres of Laval University in Quebec City enrolled 1,036 overweight volunteers, all with big potbellies that put them at especially high risk of heart problems. They were urged to cut 600 calories a day and randomly given either rimonabant or dummy pills.

After a year, those who got the higher of two doses of rimonabant had lost an average of 20 pounds and trimmed three inches from their waistlines. Nearly half of them took off 10 percent of their body weight. By comparison, those on placebos lost just five pounds.

Those getting rimonabant improved in other ways, too. Their levels of HDL, the protective good cholesterol, rose 23 percent, while their triglycerides fell 15 percent.

Despres said people taking the drug simply felt less hungry. In an earlier phase of the research, he could tell which volunteers were on the medicine by watching who passed up chocolate cake at the buffet table.

"The bottom line is we found a spectacular drop in waistlines and changes in many other risk factors that are beyond what you would ordinarily expect," Despres said.

Anthenelli's study tested the drug for 10 weeks on 787 pack-a-day smokers who wanted to quit but could not. A longer follow-up will see how well they stay off, but in the short run, 28 percent shunned cigarettes for at least a month, compared with 16 percent on dummy pills.

Especially important, Anthenelli said, is that those on the drug gained little or no weight, and a third of the successful quitters actually took off pounds at the same time. Ordinarily, smokers gain six to 10 pounds when they quit.

Some people had minor digestive side effects at first, but they usually went away.

"This is good news. The drug shows promise," said Dr. Sidney Smith, cardiovascular chief at the University of North Carolina. "However, I strongly believe lifestyle changes should be the foundation of what we do. I would not want to see patients turn to a pill as the first approach."

In all, seven large studies with rimonabant are in the works. They involve 6,600 volunteers who want to lose weight and 6,500 who want to quit smoking.