Tuesday, Nov 25, 2003
South San Francisco, Calif. -- November 25, 2003 --Genentech, Inc. (NYSE: DNA) and Roche (SWX Zurich) today announced that a Phase II study of the investigational drug Avastin (bevacizumab) plus 5-FU/Leucovorin chemotherapy in 209 previously-untreated metastatic colorectal cancer patients showed a 29 percent improvement in median survival, the primary endpoint, which did not achieve statistical significance. The study also showed a 67 percent prolongation in median progression-free survival, which was highly statistically significant, in patients treated with Avastin plus 5-FU/Leucovorin compared to 5-FU/Leucovorin alone.
"We're encouraged that a survival trend was observed and that patients also experienced a statistically significant improvement in progression-free survival, which is clinically meaningful for patients with metastatic cancer and consistent with the results of our Phase III trial," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations, and chief medical officer. "We filed the Biologics License Application for Avastin in September, and we continue to expect FDA approval no later than the end of the first quarter of 2004."
This randomized, controlled, multi-center study enrolled patients who were not optimal candidates to receive first-line CPT-11. In this Phase II study, the addition of Avastin to 5-FU/Leucovorin was well tolerated and the safety profile was consistent with that seen in previous Avastin clinical trials in colorectal cancer. Only Grade 3 hypertension, easily managed with oral medications, and asymptomatic proteinuria were increased in this trial. As in the pivotal Phase III study, although uncommon, the incidence of gastrointestinal perforation may be increased by the addition of Avastin to chemotherapy (two cases, 2 percent).
Results of the 900-patient pivotal study of Avastin plus the IFL chemotherapy regimen (5-FU/Leucovorin/CPT-11) were announced earlier this year and showed that Avastin plus the IFL regimen improved median survival by approximately five months, compared to patients treated with chemotherapy alone (20.3 months versus 15.6 months). These data were the basis for the Biologics License Application (BLA) for Avastin in metastatic colorectal cancer, which was submitted to the U.S. Food and Drug Administration (FDA) in September.
About VEGF and Tumor Angiogenesis
The link between angiogenesis and cancer growth has been discussed by many researchers for decades, but it wasn't until 1989 that a key growth factor influencing the process, Vascular Endothelial Growth Factor (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 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.
Based on preclinical and clinical studies showing that 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 solid tumor cancers and hematologic malignancies. 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 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 12 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.
Headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche employs roughly 65,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.
The statement made in this press release relating to the expected time frame for FDA approval of Avastin is forward-looking and actual results could differ materially. Among other things, the timing of FDA approval could be affected by unexpected safety or efficacy issues, discussions with the FDA, the need for additional clinical studies or the failure to receive FDA approval.