Genentech Announces Resubmission of Supplemental Biologics License Application for Avastin in Combination with Paclitaxel for First-Line Metastatic Breast CancerSOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Aug 24, 2007 - Genentech, Inc. (NYSE:DNA) announced today that the company resubmitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Avastin(R) (bevacizumab), in combination with paclitaxel chemotherapy, for patients who have not received chemotherapy for their locally recurrent or metastatic breast cancer. The resubmission, based on the pivotal Phase III trial E2100, marks the beginning of a six-month review period by the FDA.
In September 2006, the company received a Complete Response Letter from the FDA requesting additional information from the trial, including an independent, blinded review of patient scans for progression-free survival (PFS), the primary endpoint of the trial. The results of the independent review are consistent with the magnitude of benefit initially assessed by Eastern Cooperative Oncology Group (ECOG) trial investigators and presented at the 2005 annual meeting of the American Society of Clinical Oncology (ASCO). No new safety signals emerged outside of those known to be associated with Avastin.
"We would like to thank ECOG investigators for their work on this study, which showed Avastin provided a significant clinical benefit for advanced breast cancer patients in the trial," said Hal Barron, M.D., senior vice president, Development and chief medical officer. "The data from the blinded independent analysis support the original interim results presented by ECOG investigators. We look forward to our continued collaboration with the FDA and ECOG on this resubmission, as it represents an important milestone in our effort to develop novel therapies for breast cancer patients."
According to the American Cancer Society, an estimated 178,000 women will be diagnosed with breast cancer and approximately 40,000 will die from the disease in the United States in 2007. Among women, breast cancer is the most common form of the disease, excluding skin cancer, and the second leading killer after lung cancer.
Avastin is being studied worldwide in more than 300 clinical trials and in more than 20 different tumor types, including for its potential use in adjuvant (therapy given after surgery to help decrease the risk of cancer recurrence) and metastatic colorectal, renal cell (kidney), breast, pancreatic, non-small cell lung, prostate and ovarian cancers.
E2100 was a multicenter, randomized, and controlled clinical trial that enrolled 722 patients with previously untreated, locally recurrent or metastatic breast cancer. It was sponsored by the National Cancer Institute, part of the National Institutes of Health, under a Cooperative Research and Development Agreement between NCI and Genentech, and was conducted by a network of researchers led by the ECOG.
Results from the interim analysis presented at ASCO 2005 showed that patients treated with Avastin plus paclitaxel, a standard chemotherapy, experienced a near doubling in median PFS compared to those treated with paclitaxel alone (11 months versus 6 months). This analysis also showed that patients treated with Avastin had a doubling in overall PFS compared to those treated with paclitaxel alone (based on a hazard ratio of 0.50). A preliminary assessment of safety showed that serious (Grade 3/4) adverse events that occurred more often in the Avastin arm included neuropathy, hypertension and proteinuria.
Patients enrolled in the E2100 trial were randomized to receive weekly treatment with paclitaxel, with or without Avastin administered 10mg/kg every 14 days. 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(R) (Trastuzumab) or were unable to receive treatment with Herceptin. Patients who had received adjuvant taxanes in the 12 months prior to study entry, patients with a prior history of blood clots or who were receiving blood thinners, and patients with brain metastases were not eligible to enroll in this study. For full Prescribing Information and Boxed Warnings on Herceptin, visit http://www.herceptin.com.
Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the lifecycle of a tumor. By inhibiting VEGF, 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.
Avastin has a well-characterized safety profile in its approved indications. There have been more than 200,000 patients treated to date. 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.
Founded more than 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, California, 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.
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Posted: August 2007