Promising but early results from an experimental Genentech ( DNA) cancer drug are reigniting interest in a novel way to kill tumors by cutting off their food supply.

Solid tumors need blood to live and grow, so they release growth factors that encourage the formation of new blood vessels from which they can feed, a process called angiogenesis. Medical researchers have long hypothesized that if a drug could be developed to block angiogenesis from occurring, tumors would be starved of blood and die, or at least stop growing.

Theory, of course, doesn't actually help patients dying of cancer. More than 40 biotech firms are experimenting with various "antiangiogenesis" drugs, with none even close to approval so far. In fact, one such company, EntreMed ( ENMD), has the ignominious distinction of hyping -- through a front-page New York Times story in 1998 -- one of the biggest duds in biotech investment history.

But biotechs keep plugging away because there's a huge pot of gold at the end of the rainbow: a market potential that exceeds $10 billion in the U.S. alone, based on the 750,000 patients who currently receive treatment for solid tumors, according to a Merrill Lynch estimate.

Last week, Genentech offered some hope for fans of this fledgling field of cancer research. A midstage study of its experimental drug Avastin was stopped early because the drug met its clinical goals faster than expected. The study, conducted by the National Cancer Institute, showed Avastin to be effective in patients with advanced kidney cancer who had already failed chemotherapy.


Of course, "effective" has to be better defined. In this case, Avastin patients' tumors grew slower than tumors in placebo patients. But all the patients were terminally ill, and Avastin did not prolong their lives.

Sounds bleak, but in cancer research, this is progress. Genentech released news about the successful test on Oct. 25, which pushed the company's shares up 10% through the end of the week.

J.P. Morgan biotech analyst Frank Berger, in a research note, called the recent Avastin results a "defining event for Genentech's bio-oncology franchise," adding that the study, "despite modest Avastin treatment benefits, delivered impressive proof-of-principle data, in our view." Berger rates Genentech a buy, and his firm has done underwriting for the company.

Avastin has got the biotech buzz going because it might just be the right kind of antiangiogenesis drug. Specifically, it targets vascular endothelial growth factor, a protein first discovered by Genentech that seems to play a big role in jump-starting the formation of new blood vessels for cancerous tumors. Genentech is currently conducting late-stage tests using Avastin in breast, colorectal and lung cancer. Earlier-stage tests using the drug, both alone and in combination with other chemotherapy treatments, also are being conducted.

Merrill Lynch analyst Eric Hecht believes that if these late-stage tests prove positive, Avastin could reach the market in 2003. Hecht rates Genentech a buy, and his firm doesn't have a banking relationship with the company.

Other Biotechs' Cancer Drugs

Genentech is not the only biotech firm trying to develop an anti-VEGF drug. (Pronounced "anti-Veg -- as in vegetable -- F.")

Imclone ( IMCL) is conducting early human tests of a drug it calls IMC-1C11. Tuesday, the company also presented preclinical (very, very early) data on another drug dubbed FLT-1antibody.

Celgene ( CELG), MedImmune ( MEDI), Regeneron ( REGN) and Ribozyme ( RZYM) also are working on other types of antiangiogenesis drugs. (In fact, check out Celgene's Web site for a cartoon simulation of the process in action.)

Now, while biotechs like Genentech are well along in their development of antiangiogenesis drugs, there are still plenty of opportunities for these drugs to fall flat on their face.

Drugs such as Avastin, because they inhibit the growth of blood vessels, have to be very safe. Think about it, what happens if the drug stops blood vessels from growing in healthy parts of your brain or some other vital organ? The safety issue here is magnified even further because many doctors foresee the use of antiangiogenesis drugs as long-term, or chronic therapy. That means a patient could have his tumor removed or destroyed with chemotherapy, and then be given drugs like Avastin for life to stop the tumor from reforming.

"This is an area of cancer research where we have to be really careful about safety side-effects and the selectivity of the drug's targets. This will result in much longer and more complex Phase 3 trials," says John McCamant, editor of the Medical Technology Stock Letter. "But the early Avastin results feed my optimism that one day we might be able to treat cancer like a chronic disease," he adds.

In fact, Genentech ran into trouble earlier this year when it tested Avastin in patients with nonsmall cell lung cancer. Some of the patients suffered serious pulmonary bleeding episodes, resulting in four deaths.

Prying tumors away from the blood buffet, it seems, is still a lot harder to accomplish than it is to explain.