Success for New Cancer Drug

A drug that starves tumors of oxygen and nutrients has prolonged the lives of patients with colorectal cancer in a clinical trial, providing what doctors said yesterday was the first convincing validation of a new approach to treating cancer. The results of the late-stage clinical trial, announced yesterday by the drug’s developer, Genentech, came as a surprise to many analysts and scientists because the tumor-starving approach had failed to work in many previous attempts. Genentech itself had failed in using its drug, Avastin, to treat breast cancer. But yesterday Genentech said that patients given Avastin along with conventional chemotherapy lived significantly longer than those who were given the chemotherapy alone. The benefit “far exceeded what the study was designed to demonstrate,” the company said.

Genentech’s stock soared 45 percent as securities analysts, many of them previously skeptical of Avastin, quickly reversed themselves and upgraded their ratings of the company. Genentech shares closed up $16.95, to $54.85, its highest level since January 2002. “This is to my knowledge the first major randomized study that validates the concept” behind Avastin and similar drugs, said Dr. Leonard Saltz of Memorial Sloan-Kettering Cancer Center in New York, an authority on colorectal cancer. “And that is huge.” Still, he said, Avastin will probably extend lives by only a few months. “Cancer is not cured,” he said, but added, “If we keep making those modest incremental steps forward, after a while the steps add up.” Avastin works by blocking the formation of blood vessels that deliver oxygen and nutrients that tumors need to grow. This approach to cancer treatment generated great excitement in 1998 after a front-page article in The New York Times described the success of Dr. Judah Folkman, a professor at Harvard and Children’s Hospital in Boston, in eradicating tumors in mice using drugs other than Avastin.But in testing in people, seven such drugs failed in Phase 3 clinical trials, the final stage of testing, said Dr. William Li, president of the Angiogenesis Foundation, a nonprofit organization in Cambridge, Mass., that promotes the blocking approach to cancer treatment. Angiogenesis is a scientific term for the formation of blood vessels.Dr. Li said there were 65 drugs in clinical trials that work at least partly by blocking angiogenesis. Besides Avastin, two other drugs, one developed by Aeterna Laboratories of Quebec City, Canada, and the other by Novartis, the Swiss drug giant, are in Phase 3 trials.Dr. Li said the earlier failures might have been because drug companies had not yet learned how to apply the technique. “We don’t know what the right targets are,” he said. “We don’t know what the right drugs are. We don’t know what the right tumors are. And we don’t know who the right patients are,” he said. “We’re feeling our way through this.” Dr. Folkman, who has been working on anti-angiogenesis drugs for 30 years, called the Genentech news exciting but said he never doubted the approach would work. Some other drugs that have shown effectiveness against cancer, like thalidomide to treat multiple myeloma, work at least partly by blocking blood vessel formation, he said. But the Avastin results provide a clear proof, he said, because Avastin “is a pure angiogenesis inhibitor.”Because of the results of the Phase 3 trial, analysts said Genentech, a biotechnology company based in South San Francisco, Calif., would be able to apply soon for approval of Avastin. The drug could then be on the market early in 2004, sooner than expected. “This is going to change the way we think about treating cancer patients,” said Dr. Susan Desmond-Hellmann, the company’s chief medical officer. “We’ll look back and say this day was history.” Genentech has several other drugs that could be approved in the next year, like Raptiva for psoriasis and Xolair for asthma, which won the endorsement of a Food and Drug Administration advisory committee last week.But Avastin is probably the most important for the company because of its sales potential, which some analysts put at more than $1 billion a year, and because Genentech will receive all the profits from the drug. It must share Raptiva and Xolair profits with other companies.Genentech did not announce the detailed results from the clinical trial, which will be presented at the American Society of Clinical Oncology meeting starting May 31 in Chicago. The conference, which took the unusual step of accepting the Avastin paper as a last-minute submission, prohibits scientists from releasing details in advance. (Source: New York Times, ANDREW POLLACK, 20 May 2003)