Roche and Genentech’s anticancer drug Avastin failed to meet its primary endpoint in a Phase III trial involving 1,000 men with late-stage hormone-refractory prostate cancer (HRPC). The Cancer and Leukemia Group B study 90401, sponsored by the NCI, found adding the antiangiogenesis drug to chemotherapy and prednisone had no benefits on overall survival.
The disappointing Avastin results follow less than a week after sanofi-aventis reported positive data from a Phase III trial with its HRPC candidate. The study showed that adding cabazitaxel to prednisone improved overall survival and boosted progression-free survival in patients whose disease had progressed following treatment with docetaxel-based chemotherapy. The TROPIC trial compared a combination of cabazitaxel and prednisone with mitoxantrone plus prednisone.
Roche has been undergoing something of a late-stage trial results rollercoaster over the last few weeks. The negative prostate cancer trial data comes less than a month after the firm reported positive data from a Phase III study with Avastin against ovarian cancer. This trial demonstrated that maintenance therapy with Avastin following surgery and chemotherapy significantly boosted progression-free survival. Just the day before that, however, the company reported late-stage trial data that showed adding Avastin to chemotherapy in patients with advanced or metastatic/inoperable gastric cancer had no benefits on overall survival.
Safety also appears to remain an issue with Avastin. While detailed assessments from the latest prostate cancer study are ongoing, Roche confirmed that the preliminary data flagged the same severe adverse events observed in other pivotal Avastin trials, including neutropenia and fatal infections.
Avastin is not the only Roche drug demonstrating safety concerns. The late-stage antibody Ocrelizumab has also been linked with serious and sometimes fatal treatment-related opportunistic infections. The humanized anti-CD20 mAb is being developed in partnership with Biogen Idec, and just last week the companies confirmed that they were halting Ocrelizumab Phase III development for rheumatoid arthritis due to safety issues. Trials with Ocrelizumab in lupus nephritis patients had previously been stopped for the same reasons, although Phase II trials in patients with multiple sclerosis are ongoing, the companies noted.
The safety issues must have come as a serious blow to Roche and Biogen Idec. In December 2009, the companies had reported positive data from the first Phase III trial of ocrelizumab in RA, which showed that combining the drug with methotrexate significantly improved signs and symptoms of the disease.
Safety issues aside, Avastin, is remains Roche’s biggest-selling pharmaceutical. It achieved total sales of over CHF 6.2 billion (about $5.9 billion) in 2009, up 21% on 2008. Sales of the drug represent 16% of all Roche’s pharmaceutical division sales in 2009. It is currently approved in the U.S. and Europe for treating advanced colorectal, gastric, non-small-cell lung, and kidney cancers. In Japan approvals currently cover the advanced colorectal and non-small-cell lung cancer indications.
Avastin is also approved in the U.S. for the treatment of patients with advanced glioblastoma, although the European Agency’s Committee for Medicines for Human Use gave a negative opinion on approval of the drug for this indication in December 2009. The European filing was based on the same trial data used for the U.S. submission.
According to Roche, both investigator-led studies and a large-scale Phase III trial in over 900 patients with newly diagnosed glioblastoma multiforme are now under way. During 2009 a regulatory filing was also made in Switzerland for the relapsed glioblastoma indication and submissions were separately filed in the EU, U.S., Japan, and Switzerland for the use of Avastin in combination with standard chemotherapy in the first-line treatment of metastatic breast cancer.
In its 2009 annual report Roche stated that over 450 trials involving some 40,000 patients are currently investigating the use of Avastin in about 30 different tumor types.