Betting On A New Cancer Drug

(Abstract from the pharmaceutical pipeline database
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For decades, Bristol-Myers was the king of oncology. Then it lost patent protection on its blockbuster medications and its lead in research to nimbler biotech companies. Now the company is hoping that a long-planned comeback in cancer research can drive a turnaround from one of the darkest periods in its corporate history.

Dasatinib (whose tentative trade name is Sprycel) isn't a silver bullet for the company's woes, but it represents a promising first result from years of expensive research. Developed in Bristol-Myers's own labs, dasatinib has already won approval from a Food and Drug Administration advisory panel and is expected to win full FDA approval by June 28, just 31/2 years after it was first tested in patients. That would make it one of the fastest trips ever through the U.S. regulatory process.
The company has three other compounds in human studies for a variety of cancers, with hopes that they might be approved before the end of the decade. And the company is seeking to expand uses for the colorectal cancer drug Erbitux that it co-markets with ImClone Systems Inc. in a bid to bolster its sales.
"They're making progress," says Tim Anderson, an analyst at Prudential Equity Group. But he cautions, "I don't think they're there with a fully built-out franchise yet."
Converting this emerging portfolio of drugs into a robust revenue stream will take years. In the meantime, a healthy pipeline may be a lure for suitors. Lately, the company has been at the top of the list of potential drug industry takeover targets. Many analysts believe only uncertainty over whether the Federal Trade Commission will challenge an agreement that protects the patent of Plavix, the company's biggest seller, is keeping potential acquirers at bay. Plavix helps prevent formation of blood clots.

A Bristol-Myers spokesman, citing company policy, declined to comment on takeover speculation.
Bristol-Myers paved the way for some of the earliest cancer drugs. Beginning in the 1970s, it introduced a steady stream of chemotherapy agents, including platinum-based drugs such as carboplatin and the blockbuster Taxol for breast cancer. In 2000, its annual sales of oncology drugs peaked at $2.7 billion.
But after the U.S. patent for Taxol expired that year, the company's overall cancer drug sales tumbled to $1.5 billion by 2005. At the same time, momentum in oncology shifted to new so-called targeted drugs, designed to attack tumors directly with less-toxic effects than are associated with chemotherapy. Thanks in part to the high prices the new agents could command, drugs such as Genentech Inc.'s Herceptin and Novartis AG's Gleevec became blockbusters, vaulting those companies to the lead in cancer sales.

In late 2001, Bristol-Myers paid $2 billion for rights to ImClone's targeted colon cancer remedy Erbitux, only to have the FDA reject the drug a few weeks later. (The company ultimately renegotiated its deal with ImClone and the drug was eventually approved.) Then the company was rocked by a scandal involving inflated product sales to wholesalers -- a practice known as channel stuffing.

As they plotted their way out of the turmoil, company officials determined to regain prominence in cancer drugs. "This is one of the pillars upon which our company has been built," says Frank Pasqualone, head of Bristol-Myers's oncology business.
A major effort was directed at dasatinib, which was discovered by immunologists at Bristol-Myers and then found to have a molecular structure that led company scientists to believe it could inhibit two cancer causing genes. One is known as src, which is active in the breast and other solid tumors; the other is abl, which is what Gleevec blocks in patients with chronic myelogenous leukemia, or CML. Applied to human cancer cells in a test tube, the drug produced stunning results: It was as much as 300 times more potent than Gleevec. A big question was whether such potency, and its ability to home in on several mutations of the abl gene, would make it too toxic for patients.

In late 2003, doctors at M.D. Anderson Cancer Center, Houston, and the University of California at Los Angeles, began testing it in the first patients. Six months later, they saw the first major response: the drug had sharply reduced levels of the mutant gene from patients' bone marrow. "We knew we had a direct impact on the disease," says Robert LaCaze, the company's vice president for global oncology marketing. "It was a lot sooner than we had anticipated."

Since then, dasatinib has been tested on several hundred patients, yielding more convincing evidence of its benefit. Side effects include fluid retention and nausea. An FDA advisory panel voted overwhelmingly two weeks ago to recommend approval of dasatinib for chronic myelogenous leukemia patients who are resistant to Gleevec. Barring last-minute surprises, the company expects the FDA, which typically follows the advice of its panels, to make a decision by June 28.
Doctors say the new drug, and potentially a similar new compound from Novartis that is considered about a year behind dasatinib, offers hope for patients who don't respond to or can't tolerate Gleevec.

The next step is to establish dasatinib as a front-line treatment, and thus make it a direct rival to Gleevec and its $2.2 billion in annual sales. Trials are already under way to test the drug against Gleevec. The move will be tough even if those trials succeed, because Gleevec is well established in the market with impressive long-term results, doctors and analysts say. About 10,000 new cases of CML are diagnosed in the U.S. each year and a recent five-year follow-up of patients on Gleevec indicates that fewer than 5% of them per year become resistant to the drug.

Still, some analysts' estimates for dasatinib sales in 2010 range from $500 million to nearly $1 billion based on usage with patients who failed with Gleevec and on expectations that a combination of the drugs will be used.

Dasatinib may prove to be effective against other types of cancers. Once a new drug reaches the market, it is available for doctors to try with other patients. In any event, Bristol-Myers is testing the drug against other cancers with hopes of broadening its market well beyond CML.

For more information about current therapies in development visit the drug pipeline database

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