Tuesday, Jun 8, 2004
New Orleans -- June 8, 2004 --Genentech, Inc. (NYSE: DNA) today announced results from a Phase II study evaluating the combination of Avastin (bevacizumab) and gemcitabine chemotherapy in the treatment of metastatic pancreatic cancer and additional analyses from the pivotal Avastin Phase III trial in metastatic colorectal cancer. These studies were part of more than 20 abstracts evaluating Avastin in the treatment of seven different cancers presented at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO).
"This has been an important ASCO meeting. Physicians presented some truly exciting data from our broad Avastin clinical trial program, which is investigating Avastin's potential beyond metastatic colorectal cancer," said Gwen Fyfe, M.D., Genentech's vice president, Clinical Hematology/Oncology. "These studies provide preliminary evidence that angiogenesis inhibition with Avastin has activity in a range of difficult-to-treat cancers, and support Avastin's potential to be combined with both chemotherapy and other targeted treatments."
A Phase II Study of Avastin Plus Chemotherapy in Metastatic Pancreatic Cancer (Abstract #4009)
This multicenter, single-arm Phase II study, presented by Hedy Kindler, M.D., of the University of Chicago Medical Center, summarized safety and efficacy data from 45 patients with metastatic pancreatic cancer who received treatment with Avastin plus gemcitabine chemotherapy. At the time of analysis, 42 patients were evaluable for response.
In this study, the estimated one-year survival was 54 percent and the median time to disease progression was 5.8 months. The results suggest that 21 percent of patients (9/42) experienced a partial response to treatment lasting a median of 9.4 months and 45 percent of patients (19/42) achieved stable disease lasting a median of 5.4 months. Median survival was nine months.
Reports of Grade 3 or 4 adverse events were: neutropenia (33 percent, 14/42); leukopenia (30 percent, 13/42); thrombocytopenia (7 percent, 3/42); thrombosis (12 percent, 5/42); and one report each of hypertension, proteinuria and headache. There was one fatal gastrointestinal bleed and one fatal gastrointestinal perforation.
Avastin Plus 5-FU/Leucovorin Prolongs Progression-Free Survival in First-Line Metastatic Colorectal Cancer (Abstract #3516)
Fairooz Kabbinavar, M.D., of the University of California at Los Angeles, presented results from a randomized Phase II study of Avastin plus 5-FU/Leucovorin chemotherapy compared to 5-FU/Leucovorin alone in 209 patients who were not optimal candidates to receive first-line CPT-11 chemotherapy because of age or performance status. The study showed a 29 percent improvement in the primary endpoint of median survival from 16.6 months in the Avastin and chemotherapy arm to 12.9 months in the chemotherapy arm. Although this improvement was not statistically significant, it was clinically meaningful for patients with metastatic colorectal cancer and consistent with the results of the pivotal Avastin trial.
Median time to disease progression was 9.2 months in the Avastin plus chemotherapy arm, compared to 5.5 months in the chemotherapy arm. Patients receiving Avastin plus chemotherapy achieved an overall response rate of 26 percent (27/104), compared to 15 percent (16/105) in the group receiving chemotherapy alone. The duration of response was 9.2 months with Avastin plus chemotherapy, compared to 6.8 months with chemotherapy alone.
Adverse events in this Phase II study were consistent with those seen in previous Avastin clinical trials in colorectal cancer. Sixteen percent of patients (17/104) in the Avastin plus chemotherapy arm experienced Grade 3 hypertension compared to 3 percent (3/105) in the chemotherapy arm. Grade 3 proteinuria occurred at a rate of 1 percent (1/104) and gastrointestinal perforation occurred at a rate of 2 percent (2/104) in the Avastin plus chemotherapy arm.
A Combined Analysis Shows That Avastin in Combination with 5-FU/Leucovorin Improves Survival in Metastatic Colorectal Cancer (Abstract #3616)
A combined analysis of the pivotal Phase III trial and two Phase II trials in metastatic colorectal cancer evaluated the safety and efficacy of Avastin in combination with 5-FU/Leucovorin chemotherapy (n=249). These results were compared to a combined control group that included patients receiving either 5-FU/Leucovorin or the IFL chemotherapy regimen (5-FU/Leucovorin/CPT-11) alone (n=241). Results of this analysis showed that patients receiving Avastin and 5-FU/Leucovorin achieved a median survival of 17.9 months compared to 14.6 months in patients receiving the IFL regimen alone. Progression-free survival for patients treated with Avastin plus 5-FU/Leucovorin was 8.7 months compared to 5.5 months for patients treated with the IFL regimen alone.
"This analysis shows that across three studies, the addition of Avastin to 5-FU/Leucovorin provides a consistent improvement in median survival and progression-free survival," said Dr. Fyfe.
Investigators concluded that the adverse events in these studies were consistent with those observed in other colorectal cancer trials with Avastin, and included gastrointestinal perforations, hypertension, nosebleeds and asymptomatic proteinuria.
About VEGF and Tumor Angiogenesis
The link between angiogenesis and cancer growth has been discussed by many researchers for decades, but it was not until 1989 that a key growth factor influencing the process, Vascular Endothelial Growth Factor (VEGF), was discovered by Napoleone Ferrara, M.D., a Genentech Fellow. Dr. Ferrara and his team cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein. In 1993, Dr. Ferrara and his team at Genentech, in a study published in Nature, demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.
Avastin is a therapeutic antibody designed to inhibit VEGF, a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By binding to VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis. Avastin received approval by the U.S. Food and Drug Administration (FDA) on February 26, 2004, to be used in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for first-line metastatic colorectal cancer. For full prescribing information, Boxed Warnings on Avastin and information about angiogenesis, visit www.gene.com. For more information about Avastin, visit www.avastin.com.
Earlier this year, the National Comprehensive Cancer Network (NCCN), an alliance of 19 of the world's leading cancer centers, updated their Colorectal Clinical Practice Guidelines and added Avastin in combination with 5-Fluorouracil-based regimens -- including those using oxaliplatin or irinotecan -- to its list of treatment options for first-line advanced colon or rectal cancer.
Based on data showing that VEGF plays a broad role in a range of cancers, Genentech is pursuing a late-stage clinical development program with Avastin evaluating its potential use in various cancers, including renal cell (kidney), breast and non-small cell lung cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in prostate, ovarian, and several types of solid tumor cancers, as well as in hematologic malignancies and melanoma.
Avastin Safety Profile
The addition of Avastin to chemotherapy is generally well tolerated. In Genentech-sponsored studies, the most serious adverse events associated with Avastin were infrequent, and included gastrointestinal perforation, wound healing complications, hemorrhage, hypertensive crisis, nephrotic syndrome, and congestive heart failure. The most common Grade 3-4 adverse events (occurring in greater than 2 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 2 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.
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), and Avastin (bevacizumab) and markets all three products in the United States either alone (Avastin, which it recently launched in the United States, and Herceptin) or with Biogen Idec Inc. (Rituxan). Genentech has licensed Rituxan, Herceptin and Avastin 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. Potential oncology therapies directed at the HER pathway include Tarceva (erlotinib) and a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a therapy targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Eighteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes 13 biotechnology products directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional information about the company, please visit http://www.gene.com.
For full Avastin prescribing information, including Boxed Warnings, please call 650-225-7739 or visit www.gene.com.