FDA Grants Accelerated Approval of Avastin in Combination With Paclitaxel Chemotherapy for First-Line Treatment of Advanced HER2-Negative Breast Cancer
South San Francisco, Calif. --Â February 22, 2008 --Â Genentech, Inc. (NYSE: DNA) today announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval for AvastinÂ® (bevacizumab), in combination with paclitaxel chemotherapy, for the treatment of patients who have not received chemotherapy for their metastatic HER2-negative breast cancer. The approval is based on a Phase III study (E2100) that showed that Avastin in combination with paclitaxel chemotherapy resulted in a 52 percent reduction in the risk of disease progression or death compared to those treated with paclitaxel alone and a doubling in progression-free survival (PFS) (based on a hazard ratio of 0.48; p<0.0001). The safety profile of Avastin was consistent with our previous experience and no new safety signals were observed.
Avastin was approved in advanced breast cancer under the FDA's accelerated approval program, which allows the FDA to approve products for cancer or other life-threatening diseases based on initial positive clinical data. Genentech has shared with the FDA a summary of the results from a second positive Phase III trial (AVADO), and is expecting results from a third Phase III trial (RIBBON I) in first-line metastatic breast cancer in late 2008. A full review of both the AVADO and RIBBON I data by the FDA will be required for the accelerated approval to be converted into a full approval. As a part of our commitment to fully evaluate Avastin in breast cancer, Genentech will also submit data to the FDA from three additional randomized trials that are either ongoing or planned.
"There is no cure for metastatic breast cancer so it is important to control the disease as early and for as long as possible," said Kathy Miller, M.D., Associate Professor of Medical Oncology, Indiana University School of Medicine and lead investigator on the E2100 trial. "Now with Avastin plus paclitaxel, we can increase the time a woman's cancer is kept under control, and offer a biologic option to women who previously were limited to chemotherapies alone."
"As an oncologist who has treated women with metastatic breast cancer, I know how important the first course of therapy can be," said Susan Desmond-Hellmann, M.D., M.P.H., president, Product Development, Genentech. "New treatments are needed, and this approval provides women who have not yet received chemotherapy for their metastatic breast cancer a new option to consider with their physician and families."
Breast cancer is the second most common form of cancer and the second leading cancer killer among American women. According to the American Cancer Society, an estimated 178,000 women were diagnosed with breast cancer and approximately 40,000 died from the disease in the U.S. in 2007. Genentech estimates that 75 percent of women with newly diagnosed metastatic breast cancer are HER2-negative.
E2100 was a multicenter, randomized and controlled clinical trial that enrolled 722 patients with previously untreated, locally recurrent or metastatic breast cancer. Patients were randomized to receive weekly treatment with paclitaxel every three out of four weeks, with or without Avastin. Based on an independent, blinded review of patient scans, patients treated with Avastin plus paclitaxel experienced median PFS was 11.3 months versus 5.8 months in the paclitaxel alone arm. The independent review showed a similar magnitude of benefit relative to the initial results presented by the Eastern Cooperative Oncology Group (ECOG) at the American Society of Clinical Oncology annual meeting in 2005. A secondary endpoint of overall survival was 1.7 months longer in the Avastin-containing arm (with a hazard ratio of 0.87), supporting the primary endpoint of PFS. This improvement did not reach statistical significance (p=0.14).
Grade 3/4 adverse events that occurred more often in the Avastin arm included neuropathy (due to longer time on paclitaxel treatment), hypertension, arterial thromboembolic events and proteinuria. These safety findings were generally consistent with previous trials of Avastin plus chemotherapy and no new safety signals related to Avastin were observed.
The E2100 trial was sponsored by the National Cancer Institute under a Cooperative Research and Development Agreement and was conducted by a network of researchers led by ECOG.
Genentech's Commitment to Patient Access
With today's FDA approval, women receiving Avastin for metastatic breast cancer are eligible for the Avastin Patient Assistance program that provides free Avastin for the remainder of a 12-month period to patients who receive 10,000 mg (approximately $55,000 based on wholesale acquisition cost), regardless of insurance coverage.
Genentech is committed to patients having access to our therapies. Through its Genentech Access Solutions program, the company provides patients and healthcare providers with coverage and reimbursement support, patient assistance and informational resources. Patient assistance support is for those eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. Since 1985, when its first product was approved, Genentech has donated approximately $1 billion in free medicine to uninsured patients through the GenentechÂ® Access to Care Foundation (GATCF) and other product donation programs. Since 2005, Genentech has also donated more than $140 million to various independent, non-profit organizations that provide financial assistance to eligible patients who cannot access needed medical treatment due to co-pay costs.
Avastin is a therapeutic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein, a potent source of angiogenesis. Angiogenesis is a process that connects tumors to the blood supply. 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).
Avastin was the first anti-angiogenesis therapy approved by the FDA and with today's approval, is now approved for the treatment of the three leading causes of cancer death in the U.S.: metastatic colorectal cancer, advanced non-squamous, non-small cell lung cancer and metastatic HER2-negative breast cancer. In addition to metastatic breast cancer, Avastin is also indicated for the first- and second-line treatment of metastatic colorectal cancer (mCRC) in combination with intravenous 5-FU-based chemotherapy, and for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. Avastin is being studied worldwide in more than 300 clinical trials and in more than 20 different tumor types. For more information on angiogenesis, visit http://www.gene.com. For full Prescribing Information and Boxed warnings on Avastin, visit http://www.avastin.com.
Avastin has a well-characterized safety profile in its approved indications. The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common severe adverse reactions (NCI-CTC Grade 3-5) across clinical trials in mCRC, NSCLC, and mBC that occurred at a higher incidence (greater than or equal to 2 percent higher rate v. controls) were hypertension, proteinuria, and headache.
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.
This press release contains forward-looking statements regarding clinical study results and data, the ability of Avastin to increase the time a woman's cancer is kept under control and Avastin as a treatment option for metastatic breast cancer. Such statements are forward looking and involve risks and uncertainties such that actual results may differ materially. Actual results may be affected by a number of factors including, but not limited to, safety, efficacy or manufacturing issues, the need for additional data, data analysis, or clinical studies, difficulty in enrolling patients in clinical trials, failure to obtain full approval or otherwise maintain FDA approval, pricing, reimbursement, product withdrawals, and intellectual property or contract rights. Please also refer to the risk factors described in Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake, any obligation to update or revise any forward-looking statement in this press release.Â