Monday, Sep 29, 2003
South San Francisco, Calif. -- September 29, 2003 --Genentech, Inc. (NYSE: DNA) today announced that the company completed the filing of a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for Avastin (bevacizumab) as a treatment for first-line metastatic colorectal cancer in combination with chemotherapy on Friday, September 26, 2003. The BLA was submitted under the FDA's Fast Track designation, a program designed to potentially expedite the review of an investigational therapy for an unmet medical need, which allowed Genentech to submit individual components of the application as the company completed them. As part of the Avastin BLA filing, Genentech has also requested Priority Review designation from the FDA. If granted, a target FDA action date of six months from the completion of the BLA submission could further accelerate the approval of Avastin.
The BLA filing contains data from the pivotal Phase III study of Avastin in first-line metastatic colorectal cancer that enrolled more than 900 patients, as well as a safety database of more than 1,400 patients who have received treatment with Avastin in clinical trials.
"The American Cancer Society estimates that more than 150 patients will die every day from colorectal cancer in the United States," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations, and chief medical officer. "We feel a sense of urgency to provide Avastin to patients as quickly as possible and will continue working closely with the FDA during the review process."
The BLA filing is based on the pivotal Phase III trial that demonstrated an extension in the median survival of patients treated with Avastin plus chemotherapy of approximately five months or an increase of more than 30 percent, compared to patients treated with chemotherapy alone (20.3 months versus 15.6 months). No increases in bleeding, thrombosis, or asymptomatic proteinuria were seen in patients treated with Avastin plus chemotherapy as compared to those who received chemotherapy alone. Grade 3 hypertension, managed with oral medications, was increased in the Phase III study and gastrointestinal perforation, although uncommon, was increased by the addition of Avastin to chemotherapy.
Update on Clinical Trial Program
Genentech also announced that the analysis from a second study of Avastin in metastatic colorectal cancer is now expected in the fourth quarter of 2003. This study enrolled 200 patients with first-line metastatic colorectal cancer and randomized patients to receive either 5-FU/Leucovorin chemotherapy alone or in combination with Avastin.
"As we have previously communicated, the timing of this study is event-driven," added Dr. Hellmann. "Given the number of events reached so far, we now expect the results from this study to be reported before the end of the year."
Based on preclinical and clinical studies showing that Vascular Endothelial Growth Factor (VEGF) plays 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. Avastin is also being evaluated in earlier stage trials as a potential therapy in pancreatic, prostate, ovarian, melanoma and several types of blood cancers. To date, more than 2,000 patients have been treated with Avastin in clinical studies. For further information about Avastin clinical trials, please call 888-662-6728.
About VEGF and Tumor Angiogenesis
For decades the link between angiogenesis and cancer growth has been discussed by many researchers, but it wasn't until 1989 that a key growth factor influencing the process, VEGF, was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Dr. Ferrara and his team cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein. In 1993, Dr. Ferrara and his team at Genentech, in a study published in Nature, demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.
Avastin is an investigational therapeutic antibody designed to inhibit VEGF, a protein that plays an important role in tumor angiogenesis (formation of new blood vessels to the tumor) and maintenance of existing tumor vessels. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis.
About Colorectal Cancer
According to the American Cancer Society, colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. The American Cancer Society estimates that 147,500 new cases of colorectal cancer will be diagnosed in the United States in 2003.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Sixteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes 11 biotechnology products 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 additional information about the company, please visit http://www.gene.com.