Will This Drug End Obesity?

Its discoverer calls it "leptin," from the Greek leptos, meaning thin. Other researchers call it "OB-statin," which translates as "obesity stopper." Amgen Inc., which holds the drug's exclusive rights, hasn't decided what to call it. But for the one in three Americans who is overweight--and for millions more who simply want to shed a few--it's a weight-loss wonder drug.

OK, it has only been proven effective in mice. But that didn't dampen the reception when three separate teams of investigators reported in the July 28 issue of Science that a new, naturally occurring protein dramatically stripped away body fat when injected into genetically chubby mice.

There's not a huge market for treating fat rodents, of course. But the news likely will have weight-obsessed Americans everywhere salivating over the prospect of a magic skinny pill. And no company stands to gain more from the ensuing frenzy than biotech powerhouse Amgen, which in February snapped up the rights to products derived from the OB gene for a $20 million downpayment plus some $70 million to come. "If it works in humans, Amgen just may have bought one of the biggest products in the history of the pharmaceutical industry," says Edward M. Hurwitz, a biotech analyst at Robertson, Stephens & Co. Indeed, Amgen stock jumped 5%, to 841/4, on July 26, after an analyst leaked word of the studies. The real chase starts soon. "Provided that things go along smoothly, we will start human testing next year," says Amgen CEO Gordon M. Binder. There's no guarantee that the drug will work in humans, and a pill form--rather than injections--is probably a decade away or more. But given the $1.6 billion company's highly successful track record in speeding products through regulators, the drug could start fattening up profits shortly after the turn of the century.

Even before that happens, the research that spills out of the development process will go a long way toward answering questions about the causes of obesity, a major contributor to such health problems as diabetes, heart disease, hypertension, and arthritis. "This is a major breakthrough in understanding how body weight is regulated," says Dr. Jose F. Caro, chairman of the department of medicine at Jefferson Medical College in Philadelphia.

Scientists have long known that fatness runs in families and have theorized that at least part of the problem was genetic. Further, they have suspected that the brain regulates body weight like a thermostat controls temperature: When you gain weight, the brain signals you to stop eating and speeds up your metabolism. So they were intrigued last December when researchers led by Jeffrey M. Friedman at New York's Rockefeller University reported that they had found a gene in mice, dubbed OB, that secretes a hormone that seemed to do exactly that.

Now the scientists' first results are in. The verdict? Not only did daily injections of the OB protein dramatically reduce weight as a replacement therapy in obese mice unable to produce their own, but it also worked for overfed fat mice and normal mice. That's good news for Amgen: It means that the protein works even in mice without a genetic defect and could be "the key regulator of body fat," says Frank D. Collins, who headed the Amgen team.

ALTERNATIVE ROUTES. The other studies, by researchers at Rockefeller and at Hoffmann-La Roche Inc., obtained similar results. The Roche team also successfully injected the protein into the brain, bolstering the theory that it acts upon appetite controllers in the brain. Roche, which dropped out of the bidding for the OB gene, is looking for another way to accomplish the same thing. Paul Burn, director of the company's metabolic-disease unit, points out that some obese mice have plenty of the OB protein but fail to respond to its signal. If that's the case in people, he says, "maybe we can find another place in the pathway to intervene." Others are already devising alternatives: On July 26, Millennium Pharmaceuticals Inc. announced that it had cloned another mouse obesity gene called TUB.

Not everyone is thrilled by the prospect of a quick fix. It's fine for the clinically obese, says Arthur L. Caplan, director of the University of Pennsylvania's Center for Bioethics, but most people would be better off burning calories the old-fashioned way. "We're going to wind up spending billions of dollars because of our weakness of will."

Amgen, in fact, is counting on it.

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