Thursday, May 25, 2006
South San Francisco, Calif. -- May 25, 2006 --Genentech, Inc. (NYSE: DNA) today announced that the company submitted a supplemental Biologics License Application (sBLA) with the U.S. Food and Drug Administration (FDA) for Avastin® (bevacizumab) in combination with taxane chemotherapy for patients who have not previously received chemotherapy for their locally recurrent or metastatic breast cancer. Genentech has requested Priority Review of the application, which means that if accepted, the FDA would make its decision on the application within six months of the agency's receipt of the submission, or in November 2006. Avastin is currently approved as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy.
The sBLA submission is based on results from a randomized, controlled, multicenter Phase III trial (E2100) that enrolled 722 patients with previously untreated, locally recurrent or metastatic breast cancer. The trial assessed treatment with paclitaxel, a standard chemotherapy, with or without Avastin, and the primary endpoint was progression-free survival (PFS). In the trial, patients treated with Avastin plus paclitaxel had a 52 percent reduction in the risk of disease progression or death, based on a hazard ratio of 0.48, compared to those treated with paclitaxel alone. These results can also be stated as a doubling in overall PFS. Patients receiving Avastin plus paclitaxel had a median PFS of more than a year while patients receiving paclitaxel alone had a median PFS of approximately six months.
"In this study, Avastin, when added to paclitaxel chemotherapy, doubled the time that women with metastatic breast cancer lived without their cancer advancing, without significant added toxicities, compared to patients who received only paclitaxel," said Kathy Miller, M.D., associate professor of medicine, Indiana University School of Medicine and principal investigator for the study. "This is the first time progression-free survival has been observed beyond one year in a Phase III U.S. clinical trial in patients with metastatic breast cancer."
"These data support that Avastin, which is designed to interfere with the blood supply to tumors, may be an important part of treating metastatic breast cancer," said Hal Barron M.D., senior vice president, Development, and chief medical officer at Genentech. "This submission marks an important milestone in our ongoing effort to develop innovative therapies for breast cancer patients and to address unmet medical needs."
The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), under a Cooperative Research and Development Agreement between NCI and Genentech, Inc., and was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
The patients enrolled in this trial were randomized to receive weekly treatment with paclitaxel, with or without Avastin administered every two weeks. In addition to patients with HER2-negative metastatic breast cancer, patients with HER2-positive tumors were enrolled in the study only if they had received prior treatment with Herceptin® (Trastuzumab) or were unable to receive treatment with Herceptin. Patients who had received adjuvant paclitaxel within the previous 12 months, patients with a prior history of blood clots or who were receiving blood thinners, and patients with brain metastases were excluded from the study.
E2100 Safety Analysis
In the E2100 study, adverse events were similar to those seen in previous trials of Avastin plus chemotherapy. No new toxicities were identified as being associated with Avastin. Fatal events (Grade 5) occurred in less than 1 percent of patients enrolled in E2100. Grade 3/4 adverse events that occurred more often (equal to or greater than 5 percent) in the Avastin plus paclitaxel arm than in the paclitaxel alone arm included hypertension and sensory neuropathy. Grade 3/4 sensory neuropathy occurred in 23 percent of patients in the Avastin plus paclitaxel arm and in 17 percent of patients in the paclitaxel alone arm. Neuropathy is known to be associated with duration of paclitaxel therapy. Adverse events associated with Avastin including symptomatic congestive heart failure, serious bleeding and arterial thromboembolic events were not different in terms of incidence or severity relative to what has been previously observed in Avastin clinical trials. In addition, there was no increase in the incidence of Grade 3/4 venous thromboembolic events with the addition of Avastin to paclitaxel in this study.
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.
The FDA 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 PFS of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm).
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 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 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 December 2005, Genentech submitted a sBLA for Avastin plus chemotherapy for the treatment of patients with previously-treated metastatic colorectal cancer, and this submission is currently under review by the FDA. 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. For further information about Avastin clinical trials, please call 888-662-6728.
About VEGF and Tumor Angiogenesis
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 Breast Cancer
According to the American Cancer Society, an estimated 212,920 women will be diagnosed with breast cancer along with a much smaller number of men, and approximately 40,970 women will die of the disease in the United States in 2006. Breast cancer is the most common cause of cancer among women in the United States, and a woman is diagnosed with breast cancer in the United States every three minutes.
Genentech's Commitment to Patient Access
Genentech is committed to assisting eligible patients in accessing our therapies for approved indications, regardless of their ability to pay. Although Genentech's products are covered by most government and private insurance, Genentech established the Genentech® Access to Care Foundation (GATCF) in 1990 for its marketed products, and donates free product to eligible uninsured patients in the United States, except for Pulmozyme® (dornase alfa, recombinant), which is covered by the Genentech Endowment for Cystic Fibrosis. In 2005 alone, GATCF supported over 18,000 patients by providing approximately $200 million of free product. Genentech recently donated more than $21 million to several independent public charities that provide financial assistance to eligible patients who cannot access needed medical treatment due to co-pay costs. To learn more about these independent, public charities and potential financial assistance options, patients can speak with an Alternative Funding Specialist from Genentech?s Single Point of Contact (SPOC) group by calling 888-249-4918 or visiting http://www.SPOConline.com.
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 directly in the United States 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.
This press release contains a forward-looking statement regarding the potential of Avastin to have a part in treating metastatic breast cancer. Such statement is a prediction and involves risks and uncertainties such that actual results may differ materially. Among other things, Avastin's potential in treating metastatic breast cancer could be affected by unexpected safety, efficacy or manufacturing issues, additional time requirements for data analysis and decision-making, FDA actions, failure to receive FDA approval, competition, reimbursement, pricing, the ability to supply product, or product withdrawal. Please also refer to Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake, any obligation to update or revise the forward-looking statements in this press release.