Thursday, Jan 6, 2005
South San Francisco, Calif. -- January 6, 2005 --Genentech, Inc. (NYSE: DNA) today announced that the U.S. Food and Drug Administration (FDA) has approved an updated product label for Avastin (bevacizumab), which is approved in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for patients with first-line or previously untreated-metastatic colorectal cancer. The updated product label is in follow-up to the letter issued to healthcare providers in August 2004, regarding an increased risk of arterial thromboembolic events (ATEs) associated with the use of Avastin in combination with chemotherapy. An analysis of 1,745 patients treated in Avastin clinical trials showed that ATEs occurred in 4.4 percent of patients treated with Avastin, compared with 1.9 percent of patients who received chemotherapy alone. ATEs are defined in the label as stroke, transient ischemic attacks (TIAs), heart attack, angina and other arterial thromboembolic events. Some of these events were fatal.
"We first notified healthcare providers in August and are informing them now that the Avastin label has been updated, so they can use this information to better assess the overall benefit/risk of treating their patients with Avastin," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We believe it's important to view the potential risk of these events in context with Avastin's ability to improve overall survival in patients with metastatic colorectal cancer, a disease with a life expectancy of less than two years."
The updated Avastin product label and "Dear Healthcare Provider" letter are available by clicking the Avastin link on www.gene.com/gene/products. This information also will be posted on the FDA's web site.
As previously highlighted in the letter distributed to healthcare providers last year, advanced cancer patients over the age of 65 have an increased risk of experiencing an ATE while receiving Avastin in combination with chemotherapy. In an exploratory analysis from five clinical trials, there was a correlation between age (65 years and over) and the increase in risk of ATEs. The clinical benefit of Avastin, as measured by survival in the two principal arms of the pivotal study, was seen in all subgroups tested, including patients over 65. The subgroups examined were based on age, sex, race, ECOG performance status, location of primary tumor, prior adjuvant therapy, number of metastatic sites and tumor burden.
Avastin was approved by the FDA based on data from two trials. The pivotal trial was a large, placebo-controlled, randomized study that demonstrated a prolongation in the median survival of patients treated with Avastin plus the IFL (5-FU/Leucovorin/CPT-11) chemotherapy regimen by approximately five months, compared to patients treated with the IFL chemotherapy regimen alone (20.3 months versus 15.6 months). In addition, this study demonstrated an improvement in progression-free survival of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm).
Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By binding to VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis. Avastin received approval by the FDA on February 26, 2004, to be used in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for first-line metastatic colorectal cancer. For full prescribing information, Boxed Warnings on Avastin and information about angiogenesis, visit www.gene.com. For more information about Avastin, visit www.avastin.com.
Last year the National Comprehensive Cancer Network (NCCN), an alliance of 19 of the world's leading cancer centers, updated their Colorectal Clinical Practice Guidelines and added Avastin in combination with 5-Fluorouracil-based regimens - including those using oxaliplatin or irinotecan - to its list of treatment options for first-line advanced colon or rectal cancer.
Based on data 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 various cancers, including renal cell (kidney), breast and non-small cell lung cancers. Avastin also is being evaluated in earlier stage trials as a potential therapy in prostate, ovarian, and several types of solid tumor cancers, as well as in hematologic malignancies and melanoma.
Avastin Safety Profile
The addition of Avastin to chemotherapy is generally well tolerated. In Genentech-sponsored studies, the most serious adverse events associated with Avastin were infrequent, and included gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome and congestive heart failure. The most common Grade 3-4 adverse events (occurring in greater than two percent of patients in the Avastin arm, compared to the control group) were asthenia, pain, hypertension, diarrhea and leukopenia. The most common adverse events (occurring in greater than two percent of patients in the Avastin arm, compared to the control group) of any severity were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
About Genentech BioOncology Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), Avastin (bevacizumab) and Tarceva (erlotinib), and markets all four products in the United States alone (Avastin and Herceptin), with Biogen Idec Inc. (Rituxan) or with OSI Pharmaceuticals (Tarceva). Genentech has licensed Rituxan, Herceptin, Avastin and Tarceva to Roche for sale by the Roche Group outside of the United States.
The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e. programmed cell death), the HER pathway and B-cell biology. Potential oncology therapies directed at the HER pathway include a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a soluble human protein targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications.
Genentech is a leading biotechnology company that discovers, develops, manufactures, and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from, or are based on, Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the United States, and receives royalties or other income from companies that are licensed to market its products outside of the United States. The company has headquarters in South San Francisco, Calif., and is traded on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit please visit http://www.gene.com.
For full prescribing information, including Boxed Warnings for Avastin, please call 1-800-821-8590 or visit www.gene.com.