Sunday, Feb 12, 2006
South San Francisco, Calif. -- February 12, 2006 --Genentech, Inc. (NYSE: DNA) today announced that enrollment into AVANT, an international Phase III study of Avastin® (bevacizumab), XELOX and FOLFOX chemotherapy regimens in early-stage colon cancer, has been temporarily suspended to enable the Data Safety Monitoring Board (DSMB) to conduct a review of 60-day safety data. The DSMB?s recommendations are based on adverse events observed at a higher rate in the XELOX/Avastin arm of the study compared to the other two arms of the study (FOLFOX and FOLFOX/Avastin). In addition, the rapid recruitment in the AVANT trial (more than 200 patients per month), could prevent an adequate and timely safety assessment. The XELOX regimen consists of capecitabine and oxaliplatin and the FOLFOX regimen consists of oxaliplatin, 5-FU and leucovorin.
Excluding deaths due to recurrent colon cancer, all-cause mortality was 0.6% (4 cases) for FOLFOX (Arm A), 0.4% (3 cases) for FOLFOX/Avastin (Arm B) and 1% (7 cases) for XELOX/Avastin (Arm C). An occurrence of cardiac (2 cases) and unknown (3 cases) deaths, some of which occurred in younger patients, was noted in Arm C. Since the AVANT trial began recruitment in December 2004, almost two thirds of the target number of 3,450 patients has been enrolled, and in January 2006 alone more than 250 patients were recruited.
The DSMB will continue to monitor all adverse events in the study, including gastrointestinal perforations, an adverse event observed in previous studies of Avastin plus chemotherapy that has been observed in Avastin-treated patients in the AVANT study at a rate of approximately 1%. This is less than what has been observed in the metastatic setting (up to 2%).
"Due to the rapid enrollment of patients in the AVANT study and the ongoing need to carefully monitor safety, we believe that the DSMB's recommendation to temporarily suspend enrollment in the study is the right thing to do for patients in order to enable a more detailed analysis of safety data," said Hal Barron, M.D., Genentech's senior vice president, development, and chief medical officer.
AVANT is an international study being conducted by Roche, and is evaluating whether the addition of Avastin to chemotherapy as an adjuvant treatment following surgery can reduce the chance of recurrence in patients with Stage II and III colorectal cancer. The study will randomize 3,450 patients to the following three regimens:
About the NSABP C-08 Study
Enrollment continues as planned in a U.S. cooperative group study evaluating Avastin plus FOLFOX as an adjuvant treatment for early-stage colon cancer. Called C-08, this two-arm study is being conducted primarily in the U.S. by the National Surgical Adjuvant Breast and Bowel Project (NSABP) in collaboration with the National Cancer Institute (NCI). The study is randomizing patients to receive either FOLFOX alone or FOLFOX/Avastin. Unlike the AVANT study, this trial does not include a XELOX/Avastin arm.
The NSABP study has enrolled more than 1,600 of a planned 2,714 patients since the trial opened in 2004. The C-08 trial has an independent DSMB that reviews safety data on a regular basis. NSABP has consulted with their DSMB to review current safety data from both the AVANT and C-08 trials. The DSMB found no disparities in non-disease-related deaths or gastrointestinal perforations between the treatment arms of C-08, and has recommended that no changes be made to the conduct of the trial. The study continues to enroll patients as planned.
About Colorectal Cancer
According to the American Cancer Society, more than 150 patients die every day from colorectal cancer in the United States. Colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. The ACS estimates there were 145,290 new cases of colorectal cancer diagnosed and 56,290 colorectal cancer deaths in 2005.
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 progression-free survival (PFS) of more than four months (10.6 months in the Avastin/IFL arm compared to 6.2 months in the IFL-alone arm).
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, 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 hematological malignancies. For further information about Avastin clinical trials, please call 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 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 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, either alone (Avastin and Herceptin) or with Biogen Idec Inc. (Rituxan) or OSI Pharmaceuticals, Inc. (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. A therapeutic antibody directed at the HER pathway is currently in Phase II trials, and in early development, are a small molecule directed at the hedgehog pathway and a therapy targeting apoptosis.
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, 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 full prescribing information, including Boxed Warnings for Avastin, Rituxan, and Herceptin, or for Tarceva full prescribing information, please call 800-821-8590 or visit http://www.gene.com.