Healthcare Industry News: 5-FU
News Release - June 27, 2006
Phase III Study of Avastin(R) in Advanced Pancreatic Cancer Does Not Meet Primary EndpointGenentech Remains Committed to Broad Avastin Development Program in Multiple Tumor Types and Stages of Disease
SOUTH SAN FRANCISCO, Calif., June 27 (HSMN NewsFeed) -- Genentech, Inc. (NYSE: DNA ) today announced that a Phase III trial of AvastinŽ (bevacizumab) in combination with gemcitabine chemotherapy as first-line treatment for advanced pancreatic cancer did not meet its primary endpoint of overall survival. The trial was stopped at the recommendation of an independent data monitoring board based on an interim analysis indicating that it is very unlikely that significant differences in overall survival will be shown between treatment arms as the data mature. The study was not stopped due to safety events and no new safety concerns related to Avastin were observed in this trial. Data from the study will be presented at an upcoming medical meeting.
"We are disappointed in these results and will be evaluating the data to understand potential reasons why Avastin did not add a clinical benefit in this trial," said Hal Barron, M.D., senior vice president, Development and chief medical officer for Genentech. "Chemotherapy has had a limited impact in advancing outcomes for patients with pancreatic cancer, and treatments that may improve survival are desperately needed. We will continue to explore novel biologic and targeted therapy approaches that may lead to improved clinical outcomes for patients with pancreatic cancer."
This randomized, controlled study of 602 patients was sponsored by the National Cancer Institute (NCI) and conducted by a network of researchers led by the Cancer and Leukemia Group B (CALGB). The trial was initiated based on results from a single-arm Phase II study combining Avastin with gemcitabine in pancreatic cancer. The Phase II study results were first presented in 2003 at the annual meeting of the American Society of Clinical Oncology.
Genentech is pursuing a broad development program for Avastin that currently includes 130 clinical trials across 25 different types of cancer. As part of this program, a randomized Phase III study evaluating the addition of Avastin to a standard regimen of gemcitabine and TarcevaŽ (erlotinib) in patients with pancreatic cancer is currently being conducted by Roche.
Avastin, in combination with intravenous 5-FU-based chemotherapy, was approved by the U.S. Food and Drug Administration (FDA) in February 2004 for first-line treatment of patients with metastatic colorectal cancer, and received approval in June 2006 for second-line treatment of colorectal cancer. The company recently submitted supplemental Biologics License Applications (sBLA) to the FDA for Avastin in advanced non-small cell lung cancer, other than predominant squamous histology (April 2006), and for locally recurrent or metastatic breast cancer (May 2006).
About the CALGB 80303 Trial
This randomized, placebo-controlled, multi-center trial, known as CALGB 80303, was sponsored by the NCI, part of the National Institutes of Health (NIH), under a Cooperative Research and Development Agreement between the NCI and Genentech, and conducted by a network of researchers led by the CALGB. In this study, 602 patients were enrolled at approximately 200 sites and were randomized to receive treatment with gemcitabine plus Avastin or gemcitabine plus placebo as a first-line therapy. Patients who had received prior chemotherapy for metastatic disease, adjuvant chemotherapy within the previous four weeks or any prior treatment with gemcitabine or Avastin in the adjuvant or metastatic setting were excluded. Patients with a prior history of bleeding events and those who had a surgical procedure, open biopsy, or significant traumatic injury 28 days prior were also excluded from the study. The statistical plan included pre-specified futility analyses that were conducted and reviewed by an independent data monitoring board.
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 inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, a process that is thought to be critical to a tumor's growth and metastasis. For full prescribing information and boxed warnings on Avastin and information about angiogenesis, visit http://www.gene.com. For more information on Avastin, visit http://www.avastin.com.
Avastin, in combination with intravenous 5-FU-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. The FDA first approved Avastin on February 26, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Approval was 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). The addition of Avastin to IFL improved overall survival by 52 percent (based on a hazard ratio of 0.66). 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 6.2 months in the IFL-alone arm).
Avastin Safety Profile
Avastin has a well-established safety profile. In Genentech-sponsored studies, the most serious adverse events associated with Avastin were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome and congestive heart failure. The most common adverse events in receiving Avastin were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
About the Avastin Development Program
Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a broad development program for Avastin that currently includes 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in Phase III clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, pancreatic, non-small cell lung, prostate and ovarian cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in a variety of solid tumor cancers and hematologic malignancies. In April 2006, Genentech submitted an sBLA for Avastin plus platinum-based chemotherapy for first-line treatment of advanced non-small cell lung cancer other than predominant squamous histology. In May 2006, Genentech submitted an sBLA for Avastin in combination with taxane chemotherapy for patients who have not previously received chemotherapy for their locally recurrent or metastatic breast cancer. For further information about Avastin clinical trials, please call 888-662-6728.
About VEGF and Tumor Angiogenesis
Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. The link between angiogenesis and cancer growth has been discussed by many researchers for decades. 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 at Genentech 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, in a study published in Nature, Dr. Ferrara and his team 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.
About Pancreatic Cancer
The American Cancer Society estimates 33,730 Americans will be diagnosed with pancreatic cancer and 32,300 will die of the disease in 2006. Pancreatic cancer, characterized by early, distant spread, is the fourth leading cause of cancer death in the United States. For patients with advanced pancreatic cancer, the five-year survival rate across all stages is less than 1 percent, with most patients dying within one year of diagnosis.
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 conducting clinical development programs for RituxanŽ (Rituximab), HerceptinŽ (Trastuzumab), AvastinŽ (bevacizumab), and TarcevaŽ (erlotinib), and markets all four products in the United States, either alone (Avastin and Herceptin) or with Biogen Idec Inc. (Rituxan) or OSI Pharmaceuticals, Inc. (Tarceva).
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. An investigational antibody directed at the HER pathway is currently in Phase II trials. In early development, are a small molecule directed at the hedgehog pathway and an investigational agent targeting apoptosis.
Founded 30 years ago, 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 and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
For the full prescribing information for Tarceva and the full prescribing information and Boxed Warnings for Rituxan, Herceptin, and Avastin, please visit http://www.gene.com.
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