For all,
Reuters article on ENMD competition...(2nd 1/2 of article particularly illuminating)
ANALYSIS-Companies put faith in tumor-starving drugs
By Maggie Fox, Health and Science Correspondent
WASHINGTON, Feb 11 (Reuters) - Bristol-Myers Squibb <BMY.N> may have
backed off an agreement to produce one headline-making cancer drug, but companies are still putting their faith -- and their dollars -- into drugs that literally starve tumors.
Called angiogenesis inhibitors, the drugs stop tumors from building blood vessels to feed themselves. They made headlines last year after newspaper reports played up laboratory experiments in which the drugs seemed to cure mice of cancer.
Bristol-Myers said on Wednesday the compound it was working on with tiny biotechnology company EntreMed <ENMD.O> was too hard to make. The
compound, angiostatin, is based on a natural human protein that stops the production of blood vessels.
Stock in Rockville, Maryland-based EntreMed plunged on the news, cut virtually in half from about $24 a share to just under $13 on Wednesday.
Yet on Thursday it rocketed back up again to $25 after EntreMed President and Chief Executive Officer John Holaday said in several published interviews that his company was going ahead with plans to get human trials of angiostatin up and running this year.
Holaday also reminded investors that a related compound the company is
developing, called endostatin, showed even more promise in mice. EntreMed is working with the National Cancer Institute (NCI) to develop endostatin, a compound that, like angiostatin, stops new blood vessels from forming.
"People have confused angiostatin and endostatin," Holaday said in a telephone interview. "We are right on line with what was promised."
Wall Street was also excited by reminders that the NCI has been able to synthesize the protein upon which endostatin is based, and by a report in January's issue of the journal Cancer Research by Vikas Sukhatme and colleagues at Boston's Beth Deaconess Hospital, in which Sukhatme said they had managed to make mouse endostatin for experimental tests.
Last week, the NCI sent out a call to hospitals and clinics to find possible locations for the first clinical trials -- trials involving people instead of animals -- on endostatin.
EntreMed and several other companies have strong faith in the drugs and are racing to bring them to market. Although they take a number of different approaches, all the drugs have one goal -- choking off tumors.
This is a radically different aim from current cancer treatment, which concentrates on killing the cancer cells.
"If you look at traditional chemotherapy like a bomb, and you go in and kill everything and hope the good stuff comes back and the bad stuff dies, this is a different approach," said Dr. Lee Rosen of the University of California at Los Angeles, who is testing several drugs made by Sugen Inc. <SUGN.O>, based in South San Francisco.
Sugen is about to begin Phase III clinical trials -- the final trials before Food and Drug Administration (FDA) approval -- of SU5416, its experimental angiogenesis inhibitor.
"It's a very important advance in the treatment of cancers," Rosen said in a telephone interview. But he points out that while it is very easy to cure cancer in laboratory mice, doing so in human beings is much harder.
"Before we go and say it's the next cure for cancer or it's going to replace traditional means of treating, we've got a lot of testing to do," Rosen said.
Unlike angiostatin and endostatin, which are based on proteins naturally produced by the body, SU5416 is a synthetic drug. It literally blocks the receptors, or doorways, on blood vessel cells so that proteins cannot attach and start the process of building new blood vessels.
One of the problems with angiostatin and endostatin has been producing enough of the proteins, of reliable quality, to test in humans. Holaday hopes he has the problem licked with yeast genetically engineered to produce the human protein. But Bristol-Myers was doubtful enough about the technique to back away.
With drugs like SU5416 such problems do not come up, although other problems may arise.
Similarly, Sainte-Foy, Quebec-based AEterna <AEL.TO> is about to start Phase III trials, under NCI auspices, of its drug neovastat. Because it is extracted from shark cartilage, the company is confident of a reliable supply.
"We are using one of the most abundant shark species," Jean-Yves Bourgeois, chief financial officer of AEterna, said in a telephone interview. "Reproducibility has never been a problem."
AEterna's drug is based on the premise that cartilage does not contain blood vessels, and in fact actively produces compounds to keep them from forming.
"The 'skeleton' of a shark is all cartilage," Dr. Eric Dupont, president and chief executive officer of the company, said. "It's a convenient source."
Like Sugen, AEterna does not say its drug might replace the current harsh regimen of chemotherapy and radiotherapy for cancer patients. Instead, the drugs might be used to keep the cancer from coming back and spreading, Dupont said.
"If you can avoid the evolution of a primary tumor -- it doesn't matter which one,
whether it is prostate, breast or lung -- it has been clearly demonstrated that it
improves life expectancy in animals," he said.
Other companies are also testing drugs. Warren, New Jersey-based Celgene Corp.
<CELG.O> has licensed rights to thalidomide from EntreMed and is testing it
against cancer.
Thalidomide is a potent angiogenesis inhibitor, which is why doctors say it
caused such severe birth defects in children born to pregnant women who used it
in the 1950s and 1960s.
Bayer <BAYG.F>, British Biotech <BBG.L> and Agouron Pharmaceuticals
<AGPH.O> also have angiogenesis inhibitors in Phase III clinical trials.
Bristol-Myers says it has four other angiogenesis inhibitors in experimental
testing.
REUTERS
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