Friday, May 13, 2005
Orlando -- May 13, 2005 --Genentech, Inc. (NYSE: DNA) and Roche (SWX Zurich) today announced that data from a Phase III study (E4599) of Avastin® (bevacizumab) plus paclitaxel and carboplatin chemotherapies in first-line non-squamous, non-small cell lung cancer (NSCLC) showed the study met its primary efficacy endpoint of improving overall survival. Results from an interim analysis of this study showed that patients receiving Avastin plus paclitaxel and carboplatin had a 30 percent improvement in overall survival (or a hazard ratio of 0.77, which can also be referred to as a 23 percent reduction in the risk of death), compared to patients who received chemotherapy alone. This study showed that median survival of patients treated with Avastin plus chemotherapy was 12.5 months compared to 10.2 months for patients treated with chemotherapy alone.
These data were featured in a press briefing at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO). More detailed presentations of the data will be made during a plenary session by Alan B. Sandler, M.D., of Vanderbilt University Medical Center in Nashville (Abstract #LBA4 - Saturday, May 14, 5:10 p.m. EDT).
"The results of this Phase III study reveal, for the first time, an improvement in survival with the addition of a targeted biologic agent to standard chemotherapy in this patient population, and the first time median survival has been extended beyond one year in advanced lung cancer," said Dr. Sandler. "We also observed improvements in other measures of patient benefit, including progression-free survival and tumor response rate."
This study showed a 61 percent improvement in progression-free survival (or a hazard ratio of 0.62, which can also be referred to as a 38 percent reduction in the risk of progression). Median progression-free survival was 6.4 months for patients treated with Avastin plus chemotherapy, compared to 4.5 months for patients treated with chemotherapy alone. The response rate in patients with measurable disease was 27 percent (97/357) in the group receiving Avastin plus chemotherapy, compared to 10 percent (35/350) in the group receiving chemotherapy alone.
In previous clinical experience with Avastin in combination with paclitaxel and carboplatin in NSCLC, patients with a specific type of NSCLC called squamous cell carcinoma had a higher risk of experiencing life-threatening or fatal pulmonary bleeding. These patients were excluded from this Phase III study and the rate of life-threatening or fatal pulmonary bleeding in patients treated with Avastin was substantially reduced from prior clinical studies. A preliminary assessment of adverse events by the investigators showed that Grade 3/4/5 bleeding occurred in 4.5 percent of patients in the Avastin plus chemotherapy arm, compared to 1 percent of patients in the chemotherapy alone arm. Treatment-related deaths occurred at a rate of 2 percent (8/420) in the Avastin plus chemotherapy arm, compared to less than 1 percent (2/427) in the chemotherapy alone arm. Fatal (Grade 5) hemoptysis occurred at a rate of 1 percent (5/420) in the Avastin plus chemotherapy arm.
The preliminary safety assessment showed that the most common adverse events were neutropenia, hypertension and thrombotic events. Grade 3/4 neutropenia occurred in 24 percent of patients treated with Avastin plus chemotherapy and 16 percent of patients who received chemotherapy alone. Hypertension occurred in 6 percent of patients who received Avastin plus chemotherapy and 1 percent of patients who received chemotherapy alone. Grade 3/4 venous thrombosis occurred in 4 percent of patients treated with Avastin plus chemotherapy, compared with 3 percent of patients treated with chemotherapy alone. Grade 3/4 arterial thrombosis occurred in 2 percent of patients treated with Avastin plus chemotherapy, compared with 1 percent in patients treated with chemotherapy alone.
"Data from this study show that Avastin may have the potential to become an important new treatment option for patients diagnosed with non-small cell lung cancer," said Hal Barron, M.D., Genentech's senior vice president, development, and chief medical officer. "The data from this study are an important advance in lung cancer research and we would like to thank our collaborators at NCI and ECOG for their work on this study, as well as the many patients and their families who made the decision to participate in this study."
Genentech is discussing plans for the filing of a supplemental Biologics License Application (sBLA) for Avastin plus chemotherapy in first-line, advanced NSCLC with the U.S. Food and Drug Administration (FDA).
About the Trial Design
The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), under a Cooperative Research and Development Agreement between NCI and Genentech, Inc., and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
This is the first Phase III study to evaluate the therapeutic antibody Avastin in combination with chemotherapy in NSCLC. This was a randomized, controlled, multicenter trial that enrolled 878 patients with previously-untreated advanced NSCLC. The patients enrolled in this trial were randomized to receive treatment with paclitaxel and carboplatin chemotherapies with or without Avastin.
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 binding to VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis. For full prescribing information, including Boxed Warnings for Avastin and information about Avastin and angiogenesis, visit http://www.gene.com or 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.
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, non-small cell lung and ovarian cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in a variety of solid tumor cancers and hematologic 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 VEGF and Tumor Angiogenesis
The link between angiogenesis and cancer growth has been discussed by many researchers for decades. It wasn't until 1989 that a key growth factor influencing the process, VEGF, was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. 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.
About Non-Small Cell Lung Cancer
According to the World Health Organization, there are more than 1.2 million cases worldwide of lung and bronchial cancer each year, causing approximately 1.1 million deaths annually. The drug treated prevalence for non-small cell lung cancer is approximately 175,000 patients, of which an estimated 138,000 patients are stage IIIB/IV. Up to 25 percent of stage IIIB/IV non-small cell lung cancer patients may be ineligible for treatment with Avastin. According to the NCI, lung cancer is the single largest cause of cancer deaths in the United States and is responsible for nearly 30 percent of cancer deaths in this country. NSCLC is the most common form of the disease and accounts for almost 80 percent of all lung cancers.
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 alone (Avastin and Herceptin), with Biogen Idec Inc. (Rituxan) or with OSI Pharmaceuticals (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. Potential oncology therapies directed at the HER pathway include a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a soluble human protein 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. 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 traded on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
Roche in Oncology
The Roche Group, including its members Genentech in the United States and Chugai in Japan, is the world's leading provider of cancer care products, including anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented five products proven to provide survival benefit in different major tumour indications: Avastin, Herceptin, and Xeloda in advanced-stage breast cancer, Herceptin in early-stage HER2-positive breast cancer, MabThera in non-Hodgkin's lymphoma, Avastin and Xeloda in colorectal cancer, Avastin and Tarceva in non-small cell lung cancer and Tarceva in pancreatic cancer.
In addition to these anti-cancer agents, the Roche oncology portfolio includes a comprehensive collection of medicines that can help improve the quality of life of cancer patients: Bondronat (for prevention of skeletal events in patients with breast cancer and bone metastases, hypercalcaemia of malignancy), Kytril (for chemotherapy and radiotherapy-induced nausea and vomiting), Neupogen (for cancer-related neutropenia), and NeoRecormon (for anaemia in various cancer settings). CERA is the most recent demonstration of Roche's commitment to anaemia management. Other oncology products include Furtulon (for colorectal cancer) and Roferon-A (for hairy cell and chronic myeloid leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). The Roche Group's cancer medicines generated sales of more than 7.7 billion Swiss francs in 2004.
In addition to the medicines, Roche is developing new diagnostic tests that will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumour markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, Roche will continue to be the leader in providing cancer-focused treatments and diagnostics.
The unmatched Roche oncology portfolio as well as an extensive external innovation base through collaborations with companies and academia is what makes it possible for Roche to provide more effective cancer therapies.
In the United States Herceptin, MabThera (Rituxan), Avastin and Tarceva are marketed either by Genentech alone or together with its partners Biogen Idec Inc. (MabThera) and OSI (Tarceva). Outside of the United States, Roche and its Japanese partner Chugai are responsible for the marketing of these medicines.