OUISVILLE, Ky. - The L-Marc Research clinic stands at the geographic center of an American epidemic, where the meat-and-potatoes Midwest meets the chicken-fried South, and just across the street from a McDonald's.

The clinic is a leading recruitment post in the drug industry's multibillion-dollar war on fat. Desperate to be thin, overweight people eagerly respond to L-Marc's local newspaper ads for volunteers to test experimental weight-loss drugs. For each trial, the clinic is forced to turn away dozens of volunteers.

"I've had people crying on the phone," said Heather Hausberger, the dietitian who screens applicants. "They've tried everything. Nothing seems to work. A lot of people are looking for the quick fix, the magic pill."

Many drug makers, too, are seeking that magic pill. From pharmaceutical giants to tiny start-ups, the industry is spending billions of dollars developing obesity drugs. An estimated 200 possibilities are now in the research pipeline or under test among patients at dozens of clinics like L-Marc, according to MedMarket Diligence, a health care research firm.

Some drug makers say they are tackling fat in response to public health warnings of a national obesity epidemic - one that has been linked to diabetes, heart disease and other conditions and now accounts for more than $100 billion of the United States' $1.8 trillion annual medical bill. The obese are defined as those with a so-called body mass index of 30 or more. By that measure, obese people now make up one-third of the adult population.

But many drug industry analysts see a potentially even bigger market if such a drug also catches on among the more than 60 percent of adults in this country who are statistically overweight, those with a body mass index of 25 or more. Many experts also see a likelihood - some would say danger - that such a drug might appeal to millions who are by no means fat but would like to drop a few pounds.

"Everybody is just foaming at the mouth to make money" from obesity drugs, said Dr. Donna Ryan, an obesity researcher affiliated with Louisiana State University, which has received millions of dollars in government and drug-industry grants.

Industry forecasters say that an effective weight-loss drug could have annual sales far surpassing the current best-selling drug, the cholesterol treatment Lipitor, which reached $12 billion last year, especially now that Medicare says it will pay for "effective" obesity treatments.

Some experts caution that the complex variables of culture, environment, genetics and lifestyle that contribute to obesity may defy a mass-market solution. "One pill fits all doesn't seem like an outcome we'll be seeing on the horizon anytime soon," said Dr. Julie Gerberding, the physician who directs the federal Centers for Disease Control and Prevention.

But most of the biggest drug makers feel financially compelled to stay in the hunt. As it becomes more and more difficult to identify blockbusters, many companies see few other prospective best sellers in their research pipelines.

One of the most closely watched weight-loss treatments in late-stage clinical trials is Acomplia, made by Sanofi-Aventis, based in Paris. It works by blocking the same pleasure receptor in the brain that responds to the effects of marijuana. Test patients who took the drug for two years lost an average of 16 pounds, the company said. Sanofi-Aventis is expected to seek Food and Drug Administration approval for Acomplia by this summer.

Other approaches include a weight-loss nasal spray that a biotechnology company, Nastech Pharmaceutical, is testing in partnership with Merck. The spray contains a synthetic version of a human protein that signals a person's brain to stop eating when food reaches the intestines.

"Cures" for fat, of course, have long been staples of the herbal supplement and over-the-counter medicine businesses, as well as the diet industry. Amphetamines were widely used as diet pills in the 1950's and 1960's, before physicians recognized their addictive effects. More recently, amphetamine-like substances have been sold as over-the-counter treatments.

And the fen-phen prescription drug combination was popular during the mid-1990's, until it was found to damage patients' hearts. Indeed, the $21 billion that Wyeth estimates it will cost to settle legal claims related to fen-phen serves as a cautionary tale for any drug maker tempted to put a fat pill onto the mass market.

So might the reaction against another diet drug already on the market, Meridia, made by Abbott Laboratories, which has been linked to elevated blood pressure. Public Citizen, the consumer group, has asked for its withdrawal and an F.D.A. official listed it among five drugs that the agency needs to review.

Special Offer: Home Delivery of The Times from $2.90/week.

Continued 1 | 2 | 3 | Next>>