Avastin's trial failure could have pushed down Genentech's stock. Credit: Roche

It came as a shock, on April 21, when Roche of Basel announced that a highly anticipated phase 3 trial of Avastin in early-stage colon cancer had missed its primary endpoint. The humanized monoclonal antibody (mAb; bevacizumab), developed by the S. San Francisco, California–based Genentech, is a vascular endothelial growth factor (VEGF) blocker, and the company's best selling product. A successful trial for early-stage colon cancer would have boosted drug sales considerably, but results from the C-08 trial evaluating Avastin in combination with chemotherapy after tumor resection in 2,700 patients showed that the mAb failed to reduce the risk of recurrence. This proved a major disappointment to the Swiss pharma, which had only a month earlier completed a $46.8 billion takeover of Genentech. News of the trial failure sent Roche's shares tumbling and instigated talk that the Swiss company may have paid too much for the biotech. Had the results been known at the time of closing the deal Roche might have bought Genentech at a lower price. The good news came on May 5, when the US Food and Drug Administration approved Avastin as a therapy for recurrent glioblastoma multiforme in patients with refractory progressive disease. Avastin's approval for glioblastoma, an indication worth $300–$400 million per year, according to New York City–based senior biotech analyst George Farmer of Canaccord Adams in Vancouver, British Columbia, won't offset its loss in early-stage colorectal cancer for which analysts had estimated $1 billion per year in additional revenue. That Avastin is not active as an adjuvant in early colorectal cancer is perplexing, considering the success the drug has enjoyed in treating late-stage metastatic colorectal cancer, as well as advanced lung and breast cancers. “We know very little about the role of VEGF in the early stages of cancer progression,” says cancer biologist and translational investigator Rakesh Jain, director of the Edwin L. Steele Laboratory for Tumor Biology at Harvard Medical School in Boston. “VEGF is just the first line in making blood vessels in tumors, and there are other pathways and growth factors including inflammatory cytokines that are needed for making blood vessels and that contribute to tumor progression and metastasis.” Despite the setback, Roche is committed to testing Avastin in other programs, and in early-stage cancer. “But the potential of Avastin in other adjuvant settings, including breast and lung cancers, is questionable as well,” says Farmer. “Now in hindsight it looks like Roche overpaid, based on the outcome of that [C-08] study.”