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Genentech Touts Data on Colon Cancer Drug

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Times Staff Writer

Genentech Inc. said Monday that its experimental biotech drug Avastin improved the survival of colon cancer patients who received the medication in a large clinical trial, possibly setting the stage for a new way to treat cancer.

Wall Street drove Genentech’s shares up 45%, adding $8.7 billion to the total market value of the South San Francisco company. Industry analysts said it looked likely that the injectable drug would win Food and Drug Administration approval and could become a $1-billion-plus product.

Avastin belongs to an emerging class of drugs called angiogenesis inhibitors, which attempt to choke off tumors by closing the blood vessels that feed them.

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Although this class of drugs was hailed as a magic bullet in 1998, when researchers at Children’s Hospital in Boston showed that angiogenesis inhibitors cured cancer in mice, tests on humans until now were disappointing.

Since the late 1990s, seven eagerly awaited angiogenesis drugs made by various companies have failed to show effectiveness in the final stage of human tests. Genentech itself reported disappointing results last summer in a test of Avastin on patients with advanced breast cancer, prompting many on Wall Street to write off the product.

Genentech Chief Medical Officer Susan Desmond-Hellman said Monday that the tumors in breast and colon cancer are different and that the company had always viewed colon cancer patients as better candidates for Avastin.

“There were a lot of naysayers, but we never strayed from our belief.... We always knew this was an active drug,” she said.

Genentech said that it tested Avastin in a trial of more than 900 colon cancer patients and that the outcome “far exceeded” benefits that the human trial was designed to demonstrate. The company did not release many details. It will present more data, including the percentage of patients who responded to the drug and how much longer they lived, on June 1 at the American Society of Clinical Oncology meeting in Chicago.

Desmond-Hellman said Genentech planned to file an application with the FDA to market Avastin but wouldn’t predict how quickly the agency would respond.

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“We feel these data are very, very strong, and we will aim for filing the information rapidly,” she said.

Analysts said Avastin could reach the market by the end of this year.

“This is the first product we’ve seen for this disease that offers a survival benefit with minimal side effects. It really marks a sea change in cancer treatment,” said analyst Matt Geller of CIBC World Markets.

But some researchers were less effusive, noting that Avastin is not a cure and must be used with chemotherapy drugs, which destroy both healthy and cancerous cells.

Richard Kaplan, chief of clinical trials at the National Cancer Institute, said Avastin is one of several recent advances in the treatment of colon cancer. Last year the FDA approved the chemotherapy drug oxaliplatin.

Avastin “could be quite important, but it is almost never correct to say something is a breakthrough,” he said.

Other Studies

Genentech also is testing the drug in early-stage breast cancer, lung cancer and kidney cancer. But tests of Avastin in these diseases have not been completed and the outcome is uncertain.

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George Sledge, a cancer researcher at the University of Indiana, said it was difficult to assess Genentech’s announcement in the absence of specific results.

The typical aim of colon cancer drug trials is to extend the lives of patients beyond 12 to 14 months. Genentech’s announcement suggests that patients on Avastin surpassed that goal, Sledge said. The Genentech “patients probably lived in excess of 16 months,” he said.

He called the Avastin trial “a great proof-of-concept study.”

Colon cancer is the second-leading cause of cancer death in the U.S., and some 147,500 new cases will be diagnosed this year, Genentech said.

Avastin is a synthetic antibody that works by disrupting one of the molecular switches that spur blood vessel growth. The switch, called vascular endothelial growth factor, or VEGF, is present in varying degrees in most tumors and highly present in colon and kidney cancers.

Among Avastin’s side effects are high blood pressure and excessive bleeding.

VEGF isn’t the only switch that prompts blood vessel growth in tumors. Many of the failed anti-angiogenesis drugs blocked different switches that some researchers believe are less important than VEGF.

“If you want to block a freeway, you put a roadblock in the middle of the freeway; you don’t put bricks in the middle of the side streets,” said Fairooz Kabbinavar, a researcher at UCLA’s Jonsson Comprehensive Cancer Center. Kabbinavar was a paid investigator in the Avastin trial.

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Drug Combination

Avastin doesn’t kill the tumors outright but slows their growth by pruning the thicket of blood vessels that feed cancerous cells.

In doing so, Avastin starves tumors while creating navigable pathways that allow toxic chemotherapy drugs to penetrate tumors and do further damage.

The 900 patients in Genentech’s trial had colon cancer that had spread to other organs and was considered inoperable.

The company said that 400 patients received Avastin along with chemotherapy drugs, and 400 other patients received the chemotherapy combination alone. A third group of 100 patients received Avastin and a milder course of chemotherapy, but that group was dropped from the study after it became clear that the more powerful regimen was safe.

Genentech started working on the drug in 1989. But the field of study didn’t get much support within the drug industry until 1998, when Judah Folkman, lead cancer researcher at Children’s Hospital, identified two angiogenesis inhibitors.

His discovery was hailed by Nobel laureate James D. Watson, who told the New York Times, “Judah is going to cure cancer in two years.”

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At the time, Folkman was far more conservative in his own assessment. On Monday, Folkman called Genentech’s announcement “a major advance.... They deserve kudos and praise.”

Folkman’s own research has been licensed to Entremed Inc. in Rockville, Md.

William Li, head of the Angiogenesis Foundation in Boston, said the apparent success of Avastin would reignite the entire field of anti-angiogenesis drug research. “It’s very exciting and very significant,” he said.

Despite the failures of previous anti-angiogenesis drugs, there are 65 experimental angiogenesis inhibitors in various stages of clinical trials, Li said.

On Monday, though the Dow Jones industrial average fell 2.1%, Genentech’s shares closed at $54.85, up $16.95 for the day.

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