Monday, May 20, 2002
Orlando, Fla. -- May 20, 2002 --Genentech, Inc. (NYSE: DNA) today announced initial positive results from a randomized, double-blind, placebo-controlled Phase II study conducted by the National Cancer Institute (NCI), Surgery Branch, evaluating Avastin (bevacizumab, rhuMAb-VEGF), an investigational therapeutic antibody directed at vascular endothelial growth factor (VEGF), in patients with metastatic renal cell carcinoma (kidney cancer). Patients enrolled in this three-arm trial had failed previous treatments with Interleukin-2.
Results of the 116-patient trial (abstract #15) were presented at the annual meeting of the American Society of Clinical Oncology (ASCO). The study showed that patients with metastatic kidney cancer treated with single-agent Avastin (10mg/kg every two weeks) had a statistically significant increase in the primary endpoint, time to disease progression, when compared with patients in the placebo arm of the study. Researchers reported a 2.55 hazard ratio, which indicates that the time it took for the cancer to show measurable growth was two and a half times longer in patients who received high dose Avastin compared to patients who received placebo (approximately five versus two months).
The data presented support the results we've seen with Avastin in several other forms of cancer, said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations, and chief medical officer. Together, these studies demonstrate that the biological approach we're taking inhibiting a tumor's blood supply may have important clinical effects on serious forms of cancer.
A third arm of the trial studied patients receiving low-dose Avastin therapy (3mg/kg every two weeks). There was also a trend toward improvement in time to disease progression in the low dose Avastin arm in comparison to placebo (1.30 hazard ratio).
According to the authors, adverse events that appeared more often in the Avastin arms include nosebleeds, fever, hypertension and asymptomatic proteinuria.
The results presented are from a trial that stopped patient recruitment in October 2001. At that time, the NCI announced that the Phase II study evaluating Avastin in metastatic renal cell carcinoma had reached its pre-specified efficacy endpoint earlier than expected. Genentech continues to work with the NCI and the U.S. Food and Drug Administration (FDA) to determine next steps.
Long-Term Avastin Study Presented at ASCO (Abstract #32)
Genentech researchers presented data from 35 cancer patients with advanced cancer (17 colorectal, 12 non-small cell lung, five breast, and one prostate) who had received single-agent Avastin therapy or Avastin plus chemotherapy for at least a year. These patients were a subset of 302 patients treated with Avastin in Genentech-sponsored Phase I/II clinical trials.
Twenty-three of these patients who received Avastin therapy for more than a year had an off-treatment observation period and then resumed treatment with Avastin when their disease progressed. Of these patients, 22 patients (96 percent) achieved a response or disease stabilization on their first course of Avastin, and 13 of these patients (57 percent) experienced a response or disease stabilization on their second course of Avastin. Seventy-one percent (25/35) of patients who received more than one year of Avastin were still alive. To date the median survival of these patients has not been reached but is at least 27.5 months (up to 43+ months). All patients enrolled in the Phase I/II Avastin trials had a life expectancy of approximately one year due to the advanced nature of their disease.
Despite the poor prognosis of this select group of patients, most were still alive after two years, said Dr. Hellmann. This suggests there may be subsets of patients that are likely to benefit from long-term Avastin therapy. Our Phase III Avastin clinical trials will provide additional information about the activity of Avastin in larger patient populations.
Adverse events that appeared more often in the Avastin arms were bleeding, thrombosis, hypertension and proteinuria. The rate of hypertension was lower in patients treated for one year than in the overall Phase I/II treatment population. The rate of bleeding, thrombosis and proteinuria was the same in both groups. Patients treated for a year or more who developed bleeding or thrombosis while on Avastin were able to restart Avastin therapy after treatment for the adverse events. Thrombosis is known to be a complication of cancer and the treatment of cancer.
Avastin is a humanized therapeutic antibody designed to bind to and inhibit VEGF, a protein that plays a central role in angiogenesis, or the formation of new blood vessels. Blocking VEGF is intended to cut off a tumor's supply of oxygen and nutrients, inhibiting further tumor growth. Genentech is pursuing a broad late stage clinical development program with Avastin evaluating its potential use in metastatic breast, colorectal and non-small cell lung cancer.In December 2001, Genentech completed enrollment in a 450-patient Phase III clinical trial evaluating Avastin with Xeloda® (capecitabine) versus Xeloda alone for refractory metastatic breast cancer. Enrollment was also recently completed in the Avastin 900-patient metastatic colorectal cancer study comparing Avastin plus CPT-11/5-FU/Leucovorin (Saltz regimen), versus the Saltz regimen alone.
Most adverse events seen in the Phase II studies with Avastin in combination with chemotherapy were consistent with those of the chemotherapy alone. Adverse events seen more often in the combination arms included headache, fever, chills, bleeding, rash, hypertension, diarrhea and stomatitis, proteinuria and thrombosis.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products stem from or are based on Genentech science. Genentech manufactures and commercializes ten biotechnology products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.
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