THOUSAND OAKS, Calif. -- A 400-pound woman called to plead her case -- that she had tried every weight-loss plan known, none had worked, and could she please have the new fat-reduction drug. Then there was the obese man who didn't care about how dangerous the new drug might be, he didn't care how much it would cost, he just wanted it.
So did 1,000 other desperate obese people who contacted Amgen Inc., the Thousand Oaks biotechnology company and its outside research team, all looking for the "fat gene" drug that in dazzling tests cut body weight by as much as 40 percent in only one month.
Wall Street wants the fat drug too. In two days after the latest lab results in July, the value of Amgen's stock climbed by $900 million.
But the only living things that can get this biotech wonder drug right now are laboratory mice. Amgen won't start testing the new fat drug on people until next year, and it will be five years at best before the U.S. Food and Drug Administration approves it for sale.
Between now and then Amgen faces the same expensive, risky, Byzantine road that any experimental drug must travel in getting dTC from the lab to the marketplace. In biotechnology, the odds are 1 in 10 that a drug tested on people will ever win FDA approval, and the cost to create a new drug can top $200 million.
Underscoring that point is the fact that only a week before Amgen released its fat drug results in July, the company quietly announced some disappointing test results on a hepatitis drug it has struggled with for a decade.
Amgen's hepatitis drug might be a dud, but "the price of innovation is failure," said Cynthia Robbins-Roth, editor of Bioventure View, an industry newsletter. "In science there is no way to know where success will come from. You have to allow enough room for serendipity."
Granted, Amgen is the world's most successful biotech company and is expected to turn a $525 million profit this year on $2 billion in sales thanks to only two wonder drugs. But for years Amgen has struggled to come up with a third.
"Breakthrough drugs for diseases for which there are no cures today" is our goal, said George Morstyn, Amgen vice president for clinical development. Because molecular cell biology is on the scientific frontier, much remains unknown. "So there will be inevitable failures," he said, but if a drug does work, "the successes are going to be incredible."
Amgen got a fast start in the obesity drug derby last winter when it outbid several drug companies with a $20 million down payment to Rockefeller University in New York for rights to the school research team's discovery, the OB gene -- as in "obese." This gene, cloned from chronically obese mice, may be one of the chief regulators of body fat. It is thought the OB gene causes fat cells to produce a protein called leptin -- a name derived from a Greek word meaning thin.
A biotech drug copy of leptin was produced, mice were given daily shots and whammo, the fat mice got thinner fast.
For a month, chronically overweight mice, up to three times normal size, got daily leptin injections, and those mice lost 22 percent to 40 percent of their weight. Leptin was also injected twice daily in normal-sized mice, which also lost most of their body fat.
Jeffrey Halaas, a Rockefeller University researcher, knew something was taking place in those mice cages. Each day he would lift the mice out, weigh them and track how much they ate, but he could soon tell the leptin drug was working because the mice were getting harder to catch. The obese mice used to just sit in the corner of a cage all day. "In two weeks they were running around in cages. And they just looked much better and thinner. It was clear what was going on," he said.
So how might leptin work? Amgen's Mr. Morstyn draws a circle on a blackboard. On top are the brain's sensors that are set to maintain a certain amount of body fat. Below he draws the blood stream. As you eat, fat tissues keep sending out more leptin signals into the blood until eventually, like a gas gauge needle hitting F, the brain interprets that your stomach is full and you stop eating.
But what if, Mr. Morstyn says, drawing an arrow like a TV weather forecaster depicting a cold front coming in, leptin is added to the body by injecting a drug copy. "We're going to tell the [brain's] sensor mechanism that the amount of fat is already there by tricking it," he says.
With one of every three Americans overweight and $30 billion spent annually on weight-loss schemes, a genuine fat-reduction drug would obviously be a colossal hit. Amgen has the early lead because it already has an experimental drug and "so far the animals [tested] haven't died, turned blue or grown a second head," said Ms. Robbins-Roth. "Amgen clearly has one component that plays a critical role in obesity. But there are other components."
One fat-drug rival is Hoffmann-La Roche, the Swiss drug giant, which recently struck a research deal with Millennium Pharmaceuticals near Boston. In July, Millennium said it had cloned a mouse obesity gene called TUB, as in tubby. The firm does not have a drug version of TUB yet, but is pushing ahead so testing on animals can be done.
"The idea that you might be able to take the equivalent of Vitamin C in the morning and maintain or lose weight means there is a tremendous market," said Geoffrey Duyk, director of genomics at Millennium.