Sunday, Nov 23, 2008
South San Francisco, Calif. -- November 23, 2008 --Genentech, Inc. (NYSE:DNA) today announced that a Phase III study (RIBBON 1) of Avastin® (bevacizumab), in combination with taxane, anthracycline-based or capecitabine chemotherapies for first-line treatment of metastatic HER2-negative breast cancer, met its primary endpoint of increasing the time patients lived without their disease advancing, compared to the chemotherapies alone. The primary endpoint of progression-free survival (PFS) was assessed by the treating physicians in the study (investigator-assessed). The safety profile of Avastin was consistent with previous experience and no new safety signals were observed. The data, including additional analyses, will be submitted for presentation at a future medical meeting.
The Phase III trial (RIBBON 1) comprised two independently-powered study groups that evaluated Avastin with different types of chemotherapies in patients who had not previously received chemotherapy for their advanced HER2-negative breast cancer. In the first study group, patients received either Avastin or placebo in combination with taxane or anthracycline-based chemotherapies. In the second study group, patients received either Avastin or placebo in combination with capecitabine chemotherapy. The primary endpoint was met for both study groups.
"The findings of this study, together with the positive PFS results from the E2100 and AVADO Phase III trials, support Avastin's ability to delay cancer progression with commonly used chemotherapies in metastatic HER2-negative breast cancer," said Hal Barron, M.D., senior vice president, Development and chief medical officer. "We look forward to discussing these data with the FDA and are committed to securing full FDA approval of Avastin based on the totality of data in advanced breast cancer. We plan to submit the data from RIBBON 1 and AVADO to the FDA by mid-2009."
Avastin was approved for advanced breast cancer in February 2008 under the U.S. Food and Drug Administration's (FDA) accelerated approval program, which allows provisional approval of medicines for cancer or other life-threatening diseases. Avastin, in combination with paclitaxel, is indicated for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
A full review of data from the studies RIBBON 1 and AVADO is required for the accelerated approval to be converted into a full approval. As a part of the company's commitment to fully evaluate Avastin in breast cancer, Genentech also will submit to the FDA data from three additional randomized trials that are either ongoing or planned.
About RIBBON 1 (AVF3694g)
RIBBON 1 is an international, multicenter, randomized, double-blind, placebo-controlled clinical study that enrolled 1,237 patients with locally recurrent or metastatic HER2-negative breast cancer who had not received chemotherapy for their metastatic disease. The trial evaluated the addition of either Avastin or placebo, to taxane or anthracycline-based chemotherapies (group one), or to capecitabine chemotherapy (group two). The following chemotherapy regimens were used in the study:
In the study, PFS was defined as the time from randomization to disease progression or death, and each study group was individually powered and analyzed to detect a significant improvement in this endpoint. Secondary endpoints included objective response rate, one-year survival rate, overall survival, PFS assessment by independent review committee, and safety.
Avastin is a biologic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein that plays an important role in the development and maintenance of blood vessels, a process known as angiogenesis. VEGF is a potent activator of angiogenesis 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.
Avastin was the first anti-angiogenesis therapy approved by the FDA and is approved to treat metastatic colorectal cancer, advanced non-squamous, non-small cell lung cancer (NSCLC) and metastatic HER2-negative breast cancer. Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy; for the first-line treatment of unresectable, locally advanced, recurrent or metastatic NSCLC in combination with carboplatin and paclitaxel; and for previously untreated, metastatic HER2-negative breast cancer in combination with paclitaxel.
The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
Gastrointestinal (GI) perforation: Avastin administration can result in the development of GI perforation, in some cases resulting in fatality. GI perforation, sometimes associated with intra-abdominal abscess, occurred throughout treatment with Avastin (i.e., was not correlated to duration of exposure). Patients with GI perforation should permanently discontinue Avastin therapy.
Wound healing complication: Avastin administration can result in the development of wound dehiscence, in some instances resulting in fatality. Patients with wound dehiscence requiring medical intervention should permanently discontinue Avastin therapy. The appropriate interval between termination of Avastin and subsequent elective surgery has not been determined.
Hemorrhage: Severe, and in some cases fatal, pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and Avastin. Patients with recent hemoptysis (≥1/2 tsp of red blood) should not be administered Avastin. Other serious bleeding events occurring in patients receiving Avastin across all indications include GI hemorrhage, subarachnoid hemorrhage, and hemorrhagic stroke. In patients with serious hemorrhage (i.e., requiring medical intervention), Avastin should be permanently discontinued and physicians should initiate aggressive medical management.
Additional serious adverse events included non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure. The most common grade 3-5 (nonhematologic) and 4-5 (hematologic) events that may have occurred in Avastin indications included neutropenia, fatigue, hypertension, infection, hemorrhage, asthenia, abdominal pain, pain, deep vein thrombosis, intra-abdominal thrombosis, syncope, diarrhea, constipation, leukopenia, nausea, vomiting, dehydration, ileus, neuropathy, sensory, neurologic-other, and headache.
For full Prescribing Information and Boxed warnings on Avastin, visit http://www.avastin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for patients with significant unmet medical needs. 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 the efficacy of Avastin, and FDA full approval of Avastin, in metastatic HER2 negative breast cancer; and the submission of data to the FDA. 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, FDA actions or delays, failure to obtain full approval or otherwise maintain FDA approval, 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.