Thursday, Apr 14, 2005
South San Francisco, Calif. and Basel, Switzerland -- April 14, 2005 --Genentech, Inc. (NYSE: DNA) and Roche (SWX Zurich) today announced that an interim analysis of a Phase III study of Avastin (bevacizumab) plus paclitaxel chemotherapy in first-line metastatic breast cancer met its primary efficacy endpoint of showing an improvement in progression-free survival, compared to chemotherapy alone.
"This study is very important for two reasons: it demonstrates that Avastin has clinical benefit when used in combination with chemotherapy in first-line metastatic breast cancer and reinforces our belief that targeting angiogenesis can result in patient benefit in multiple tumor types, including colorectal and non-small cell lung cancers," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We are particularly excited about the results in this first-line study since they occurred at an early interim analysis."
The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under a Cooperative Research and Development Agreement between NCI and Genentech, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). Detailed results from this trial will be presented at an upcoming medical meeting.
"We plan to share these data with the FDA to discuss the possibility of filing a supplemental Biologics License Application for Avastin plus chemotherapy in first-line metastatic breast cancer," continued Dr. Barron. "We would like to acknowledge ECOG and NCI for their work on this study, as well as the patients and their families who participated in the trial, for their important role in identifying a potential new treatment option for women with breast cancer."
This Phase III study was a randomized, controlled, multicenter trial that enrolled 722 women with previously untreated metastatic breast cancer. The patients enrolled in this trial were randomized to receive treatment with paclitaxel with or without Avastin. Patients with HER2-positive metastatic breast cancer were not enrolled in the study unless 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 and patients with a prior history of blood clots or who were receiving blood thinners were also excluded from the study.
The safety assessment for this trial is currently being reviewed, but thus far no new signals have been observed. More detailed information about adverse events will be available when ECOG presents the full data set at an upcoming medical meeting. Adverse events in this study appeared to be similar to those observed in previous clinical trials with Avastin in combination with chemotherapy in metastatic breast cancer. Adverse events that occurred more often in the Avastin arm included neuropathy, hypertension and proteinuria. Serious bleeding and blood clots were rare in this study. Additional adverse events were similar between the two treatment arms.
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.
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 of 925 patients 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 (PFS) of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm). For full prescribing information, including Boxed Warnings for Avastin and information about Avastin and angiogenesis, visit www.gene.com or www.avastin.com.
Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a late-stage clinical development program with Avastin evaluating its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, non-small cell lung, pancreatic, ovarian and prostate 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 Genentech's clinical trials line at 888-662-6728.
Avastin Safety Profile
Avastin has a well-established safety profile. 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 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 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.
About Breast Cancer
According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. 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.
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, and Avastin, and OSI Pharmaceuticals has licensed 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 licenses several additional products to other companies. 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 http://www.gene.com.
Roche in Oncology
Within the last five years the Roche Group including its partners Genentech in the US and Chugai in Japan has become the world's leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit in different major tumour indications: Xeloda and Herceptin in advanced stage breast cancer, MabThera in non-Hodgkin's lymphoma, and Avastin in colorectal carcinoma. In the United States Herceptin, MabThera and Avastin are marketed either by Genentech alone or together with Biogen Idec Inc. Outside of the United States, Roche and its Japanese partner Chugai are responsible for the marketing of these drugs.
The Roche oncology portfolio also includes NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcaemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (hairy cell and chronic myeloid leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. The Roche Group's cancer medicines generated sales of more than 3.3 billion Swiss francs in the first half of 2004.
Roche is developing new tests, which will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumour markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, we will continue to be the leaders in providing cancer focused treatments and diagnostics.
Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland).
For full prescribing information, including Boxed Warnings for Avastin, Rituxan and Herceptin, or for Tarceva full prescribing information, please call 800-821-8590 or visit www.gene.com.