Monday, Dec 11, 2006
South San Francisco, Calif. -- December 11, 2006 --Genentech, Inc. (NYSE: DNA) today announced that an interim analysis shows that a randomized Phase III clinical study of Avastin® (bevacizumab) in combination with interferon alfa-2a therapy in patients with first-line metastatic renal cell carcinoma (mRCC) met the primary analysis endpoint by significantly improving progression-free survival (PFS) compared to interferon alfa-2a therapy alone. In addition, the early analysis indicates a trend toward improvement in overall survival in the Avastin plus interferon arm.
An independent data safety monitoring board (DSMB) has recommended that patients in the study be made aware of the results and offered treatment with Avastin. Results from the study will be submitted for presentation at an upcoming medical meeting.
RCC is the most common type of kidney cancer, accounting for nine out of 10 cases, and new treatment options are needed, as fewer than 10 percent of late-stage kidney cancer patients will live five years following diagnosis. According to the American Cancer Society, there will be 38,890 new cases of kidney cancer and 12,840 kidney cancer deaths in 2006.
''We are pleased with the results demonstrating improvement in progression-free survival in this study and plan to discuss the data and the submission of an application for a potential indication in renal cell cancer with the U.S. Food and Drug Administration,'' said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer. These results reinforce our belief that inhibiting angiogenesis by specifically blocking vascular endothelial growth factor could provide important clinical benefit across a broad range of tumor types.''
Adverse events in this study appeared to be similar to those previously reported for interferon and for Avastin. The most common adverse events that occurred more often in the Avastin plus interferon arm included bleeding, hypertension and proteinuria. Serious adverse events occurring more often in the Avastin plus interferon arm included fatigue, pneumonia and gastrointestinal perforations.
About the Study
AVOREN is a randomized, double-blind Phase III trial sponsored by Roche that enrolled 649 patients with first-line mRCC. Patients were randomized to receive either standard therapy of interferon alfa-2a plus placebo or interferon alfa-2a plus Avastin. Avastin was administered every two weeks at a dose of 10 mg/kg.
The study was originally designed to measure an improvement in overall survival; however, in prior consultation with the FDA, the primary analysis endpoint was revised to assess improvement in PFS, defined as the length of time the tumor did not grow or patient death did not occur. Other endpoints of the study included overall survival, time to progression, time to treatment failure, overall response rate and safety profile. The study protocol specified an interim overall survival analysis be performed at approximately 50 percent of events. The required events have not yet occurred for a final analysis of overall survival.
Another study of interferon plus or minus Avastin in first-line mRCC with a primary endpoint of overall survival is being conducted in the United States by the Cancer and Leukemia Group B, a national clinical research group sponsored by the National Cancer Institute. The results of this trial have not yet been reported. In addition, the company is planning a randomized study of Avastin in combination with another targeted agent in RCC.
Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in tumor angiogenesis and the maintenance of existing tumor vessels. Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information on angiogenesis, visit http://www.gene.com. For full prescribing information and boxed warnings on Avastin, visit http://www.avastin.com.
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. Avastin is also indicated in combination with intravenous 5-FU-based chemotherapy for second-line treatment of patients with metastatic carcinoma of the colon or rectum. On October 11, 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC).
The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common adverse events in patients 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, 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. 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; however it was not 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. 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. Ferrara then created a mouse antibody to this protein.
In 1993, in a study published in the journal Nature, 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 an important role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.
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 Rituxan® (Rituximab), Herceptin® (Trastuzumab), Avastin® (bevacizumab) and Tarceva® (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.