Monday, May 22, 2006
South San Francisco, Calif. -- May 22, 2006 --Genentech (NYSE: DNA) today announced a decision by Roche, following a recommendation from an independent Data Safety Monitoring Board (DSMB), to resume patient recruitment into AVANT, an international Phase III study of Avastin (bevacizumab), XELOX and FOLFOX chemotherapy regimens in early-stage colon cancer. Patient recruitment will resume upon clearance by the relevant Independent Review Boards and European Health Authorities.
The DSMB based its recommendation to resume enrollment on a detailed analysis of safety data from the trial. The halt in enrollment was implemented in order to conduct a 60-day safety review for recently recruited patients and assess occurrences of cardiac and unknown deaths in one of the treatment arms. The DSMB concluded that the current safety profile and overall mortality observed in AVANT are consistent with those seen in other early-stage colon cancer trials.
Currently, there is no indication of an imbalance of cardiac events between the treatment arms of the AVANT study. However, in order to gain further insight on the overall occurrence of cardiac events and sudden deaths, the AVANT study protocol will be amended to include a cardiac monitoring plan (CMP) that will involve an enhanced baseline cardiac assessment and additional basic cardiac investigations.
"Following rapid patient enrollment into the AVANT study, we believe the temporary halt of recruitment to assess safety was the right thing to do for patients," said Hal Barron, M.D., Genentech's senior vice president, Development, and chief medical officer. "The U.S.-based adjuvant trial, NSABP C-08, has continued to enroll as planned with no changes to its protocol. The AVANT and NSABP C-08 trials, which have different treatment arms, provide an opportunity to investigate whether adding Avastin to standard chemotherapy as adjuvant therapy may be safe and effective in patients with early-stage colon cancer."
AVANT is an international study being conducted by Roche to evaluate 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 into the following three regimens:
Since the AVANT trial was initiated in December 2004, approximately two-thirds of the target number of 3,450 patients have been enrolled. Patients who had already enrolled into the AVANT trial prior to the recruitment suspension continued treatment according to the study protocol. The data review undertaken by the DSMB, with a cut-off date of April 25, 2006, revealed that mortality from all causes in the AVANT trial, excluding deaths due to recurrent colon cancer, was 0.8% (6 cases) for FOLFOX-4 (Arm A), was 0.5% (4 cases) for FOLFOX-4 + Avastin (Arm B), and was 1.05% (8 cases) for XELOX + Avastin (Arm C). These rates are consistent with those reported in other adjuvant studies in colon cancer.
About the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-08 Study
C-08 is a U.S. cooperative group study evaluating Avastin plus FOLFOX chemotherapy as an adjuvant treatment for early-stage colon cancer. The two-arm study is being conducted primarily in the United States 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. This trial does not include a XELOX/Avastin arm.
The C-08 study has enrolled more than 2,000 of a planned 2,714 patients since the trial opened in 2004. The trial has an independent DSMB that reviews safety data on a regular basis. NSABP consulted with its DSMB to review current safety data from both the AVANT and C-08 trials and found no disparities in non-disease-related deaths or gastrointestinal perforations between the treatment arms of C-08.
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).
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 the Avastin Development Program
Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a broad development program for Avastin that currently includes more than 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in Phase III clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, pancreatic, non-small cell lung, prostate and ovarian cancers. In April 2006, Genentech submitted a supplemental Biologics License Application (sBLA) with the FDA for Avastin in combination with platinum-based chemotherapy for first-line treatment of advanced, non-small cell lung cancer (NSCLC) other than predominant squamous histology. The company plans to submit an sBLA for Avastin for the treatment of metastatic breast cancer in the second quarter 2006. Avastin is also being evaluated in earlier stage trials as an investigational agent in a variety of solid tumor cancers and hematologic malignancies. For further information about Avastin clinical trials, please call 888-662-6728.
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 will be 148,610 new cases of colorectal cancer diagnosed and 55,170 colorectal cancer deaths in 2006.
Genentech's Commitment to Patient Access
Genentech is committed to assisting eligible patients in accessing our therapies for approved indications, regardless of their ability to pay. Although Genentech's products are covered by most government and private insurance, Genentech established the Genentech® Access to Care Foundation (GATCF) in 1990 for its marketed products, and donates free product to eligible uninsured patients in the United States, except for Pulmozyme® (dornase alfa, recombinant), which is covered by the Genentech Endowment for Cystic Fibrosis. In 2005 alone, GATCF supported over 18,000 patients by providing approximately $200 million of free product. Genentech recently donated more than $21 million to several independent public charities that provide financial assistance to eligible patients who cannot access needed medical treatment due to co-pay costs. To learn more about these independent, public charities and potential financial assistance options, patients can speak with an Alternative Funding Specialist from Genentech's Single Point of Contact (SPOC) group by calling 888-249-4918 or visiting http://www.SPOConline.com.
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 conducting 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. An investigational 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 an investigational agent targeting apoptosis.
Founded 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 directly in the United States 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 the full prescribing information for Tarceva and the full prescribing information and Boxed Warnings for Rituxan, Herceptin, and Avastin please visit http://www.gene.com.