Published online 22 April 2009 | Nature | doi:10.1038/news.2009.394
Updated online: 7 May 2009

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Cancer drug hits setback

Results from early-stage colon cancer trial turn spotlight on recent acquisition.

Bevacizumab (Avastin), the first drug approved to choke off blood supply to cancerous tumours, does not work any better than chemotherapy alone in treating early-stage colon cancer, its maker has announced.

The much-anticipated results of the phase 3 clinical trial sent shares in the pharmaceutical giant Roche down 10 percent today. In March, Roche paid $47 billion to fully acquire Genentech, the South San Francisco–based biotechnology pioneer that created Avastin.

The new results have some questioning whether Roche paid too much in that struggle. After months of negotiation, the Basel, Switzerland–based Roche eventually paid $95 a share for Genentech.

"There were a lot of expectations that this trial was going to work, and I don't know why Roche didn't wait for the results," says Laurence Lasky, a former Genentech scientist who is now a partner at US Venture Partners of Menlo Park, California. Had Roche waited for this disappointing outcome, "it could have put downward pressure on the offer," Lasky says. "But it's a moot point now."

Roche and Genentech have already begun restructuring in the wake of their 'integration'. Key Genentech figures including CEO Arthur Levinson, head of product development Susan Desmond-Hellman and chief financial officer David Ebersman are leaving company management, although Desmond-Hellman and Levinson will continue to advise Genentech and Levinson will chair its new board of directors.

Roche's head of pharmaceutical commercial operations, Pascal Soriot, is the new Genentech CEO, while the former Genentech executive vice-president of research, Richard Scheller, is now head of a new Roche unit called Genentech Research and Early Development.

Data still forthcoming

The colon cancer trial compared patients receiving the monoclonal antibody Avastin along with chemotherapy for six months, followed by Avastin alone for another six months, versus patients receiving only chemotherapy for six months. Scheller said that Genentech was disappointed by the news. "It's clearly a setback," he says. "It certainly means — in the very near term — fewer revenues, which translates into less money to spend on research and development." However, Scheller says the company would continue testing bevacizumab as an adjuvant therapy in lung cancer and breast cancer and will also further analyze data from the colon cancer trial: "There's some extremely interesting aspects to the data that will be presented" at a meeting of the American Society of Clinical Oncology that starts May 29 in Orlando, Florida, he says.

Roche and Genentech also said in a statement that they "continue to believe Avastin may be active in patients with early-stage colon cancer", but that they would not share the data behind that statement until the study is presented.

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Avastin is approved in both the United States and European Union to treat later-stage colon cancer, along with some other cancers. Next month, the US Food and Drug Administration is expected to decide on whether it could also be used to treat the brain cancer glioblastoma.

Recently, however, some scientists have claimed that Avastin does not work by simply choking off a tumour's blood supply, which may in part explain why the drug has not performed as well as some had hoped it would. "There's always been a lot of controversy in the literature" about how these kinds of drugs work, Lasky says. "It's definitely not working as well as [Genentech] thought it would. Avastin just isn't perfect, and it's unclear why." 

Updated:

The US Food and Drug Administration has now approved the use of Avastin to treat glioblastoma.

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