One fat-drug rival to Amgen is Hoffmann-La Roche, the Swiss drug giant, which recently struck a research deal with Millennium Pharmaceuticals near Boston. In July, Millennium said it cloned another mouse obesity gene called TUB, as in tubby . They don't have a drug version of TUB yet, but are pushing ahead so they can test it on animals. "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.
To solve the riddle of whether Amgen's OB gene and its leptin drug are the answer to obesity, Amgen must first do more animal samples before launching tests next year on human volunteers.
When leptin is tested on people, there will be various things to watch for, such as jitteriness--Halaas notes that the mice were \o7 very\f7 active after getting the drug. Plus, obese people are likely to take the drug for a long time, which could lead to unknown side effects.
"You can imagine a whole spectrum of responses," Halaas said. And some people might not lose any weight. "We think that will be a rare occurrence, but there is no way to know for sure."
Still, Morstyn talks about leptin as a fast-track drug, and maybe getting it to market in five years. For now, Amgen must pick doctors to run its tests and decide how overweight the first batch of patients will be. Certainly, there is no shortage of plump volunteers. The Rockefeller research team is so overloaded with requests from would-be human guinea pigs that a special phone line tells callers where to send letters listing their key medical information, including their weight.
A love of science may inspire all this, but what pays for this level of research is good old-fashioned capital. Any evidence of the enormous creation of wealth possible from a couple of blockbuster drugs can be seen at Amgen's headquarters. Less than a decade ago, Amgen was a sleepy company with a few small offices in a new office park, and most everybody there knew everybody else.
Then, in 1989, Amgen's first drug, Epogen, went on sale. Of 60,000 genes in the human body, an Amgen scientist had found one gene that could produce red blood cells--the scientific equivalent of finding a marble at the bottom of a lake. Kidney disease patients now talk of Epogen as a magic potion and tell of how they no longer need blood transfusions, or are no longer bedridden, and have resumed their lives with vigor.
In 1991, Amgen's second drug, called Neupogen, came out. It spurs production of white blood cells, one of the body's key infection fighters, and is now widely used, including in cancer chemotherapy and AIDS treatment.
Both drugs can cost thousands of dollars a year per patient, but since there had been nothing else like them, they changed medicine and the company. The result: Amgen's headquarters today is a massive complex with 2,400 employees, an on-site day-care center, and a main lobby so choked with visitors that a receptionist hands out maps to help people find their way among the maze of buildings, many with elaborate security systems requiring special ID cards to enter.
Getting a new drug out of those buildings is another matter. Amgen's latest dead-end project is likely to be Infergen, a biotech copy of several human proteins. Amgen started working on the project in the mid-'80s, and the drug has been tested on people to see if it can combat the hepatitis-C virus, which can lead to liver cancer.
But news tidbits from the company's latest 700-patient trial led analysts to conclude that Amgen's test drug doesn't work any better than a similar drug already sold by giant Schering-Plough Corp.
Amgen's lab chief, Morstyn, is a bit testy about Infergen. The drug "actually works," he said, and patients "clearly have a benefit" from it. But Amgen probably will quit the case, conserving cash for more promising drugs in its portfolio, said Jim McCamant, editor of the Medical Technology Stock Letter.
One promising avenue involves MGDF, which stands for \o7 megakaryocyte growth and development factor, \f7 a gene-spliced copy of a protein that may trigger production of platelets. Platelets are the oval-shaped disks that make blood clot; hematologists consider this the final blood cell drug mystery because Amgen has already solved how to force the body to make more red and white blood cells.
Certainly a platelet drug could help bone marrow transplant, breast cancer and ovarian cancer patients facing intense chemotherapy. Chemotherapy kills both good and bad cells, often leaving patients with such a low platelet count that their blood won't clot, which can lead to intestinal bleeding, brain hemorrhages and sometimes death. All doctors can do now is halt the chemotherapy and give patients transfusions of platelets--which cost hundreds of dollars per treatment. Meanwhile, the cancer cells are free to grow.