Monday, May 19, 2003
South San Francisco, Calif. -- May 19, 2003 --Genentech, Inc. (NYSE: DNA) today announced that a Phase III study of Avastin (bevacizumab, rhuMAb-VEGF) plus chemotherapy in previously-untreated metastatic colorectal cancer patients met its primary endpoint of improving overall survival. The magnitude of the benefit observed far exceeded what the study was designed to demonstrate. The trial also met the secondary endpoints of progression-free survival, response rate, and duration of response. Genentech plans to submit data from this Phase III metastatic colorectal cancer trial to the annual meeting of the American Society of Clinical Oncology (ASCO), May 31 - June 3.
Avastin is an investigational therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays a critical role in tumor angiogenesis (the formation of new blood vessels to the tumor) and maintenance of existing tumor blood vessels. By inhibiting VEGF, Avastin is designed to interfere with processes that are critical to tumor growth and metastasis.
"The data from this important Phase III trial, which show that treatment with Avastin and chemotherapy resulted in improved survival, highlights a potentially new way to treat patients with metastatic colorectal cancer," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations, and chief medical officer. "These data strongly suggest that inhibiting VEGF - a growth factor first cloned by Genentech scientists - results in clinical benefit for colorectal cancer patients and has the potential to change the practice of treating cancer."
"This study also provides the first Phase III clinical validation of the long-pursued 'anti-angiogenic' hypothesis - that by targeting a tumor's blood supply, you may impact its viability. Based on the strength of these data, Genentech plans to discuss the filing of a Biologics License Application with the U.S. Food and Drug Administration," continued Dr. Hellmann.
This multi-center study enrolled more than 900 patients, and randomized 800 patients to receive either Avastin plus the standard of care chemotherapy (5-FU/Leucovorin/CPT-11, called the Saltz regimen) or the Saltz regimen plus an Avastin placebo. A third arm of the study treated 100 patients with Avastin plus 5-FU/ Leucovorin chemotherapy. This arm was dropped, as pre-specified, once safety with the Saltz regimen was established.
The addition of Avastin to chemotherapy was well tolerated. While bleeding, thrombosis, asymptomatic proteinuria and hypertension were identified in Phase II studies as possible safety events, only Grade 3 hypertension, easily managed with oral medications, was clearly increased in this Phase III study. Gastrointestinal perforation, although uncommon, may be increased by the addition of Avastin to chemotherapy.
Comprehensive Clinical Trial Program
Based on preclinical and clinical studies showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a late stage clinical development program with Avastin evaluating its potential use in metastatic colorectal, renal cell (kidney), breast and non-small cell lung cancers. To date, more than 2,000 patients have been treated with Avastin in clinical studies.
Results from a second Genentech study in metastatic colorectal cancer are expected later this year. The second colorectal cancer trial enrolled 200 patients who are not optimal candidates for CPT-11 as a first-line treatment and randomized subjects to receive either 5-FU/Leucovorin chemotherapy alone or in combination with Avastin.
In October 2001, a Phase II study with Avastin in metastatic renal cell carcinoma conducted by the National Cancer Institute (NCI) was stopped early after reaching its pre-specified efficacy endpoint. Results from this study were presented at last year's ASCO meeting. Based on the positive data observed in this trial, two Phase III trials in metastatic kidney cancer are scheduled to begin enrollment this year.
In addition, Phase III Eastern Cooperative Oncology Group (ECOG) studies continue to evaluate Avastin in second-line metastatic colorectal, first-line metastatic non-small cell lung, and first-line metastatic breast cancer. Additional studies are ongoing through the NCI in more than 20 different tumor types.
A Phase III study of Avastin plus Xeloda® (capecitabine) in metastatic breast cancer patients who had previously received treatment with both anthracycline and taxane-based chemotherapy regimens showed an improvement in overall response rate, although this did not translate into benefit in progression-free survival or twelve-month survival.
About Colorectal Cancer
According to the American Cancer Society (ACS), colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. The ACS estimates that 147,500 new cases of colorectal cancer will be diagnosed in the United States in 2003.
Avastin is an investigational humanized therapeutic antibody designed to inhibit tumor growth by binding to and inhibiting VEGF, a protein that plays a critical role in tumor angiogenesis (the formation of new blood vessels to the tumor), and maintenance of existing tumor blood vessels. For further information about Avastin clinical trials, please call 888-662-6728.
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 originated 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. For press releases and additional information about the company, please visit http://www.gene.com.