Avastin Plus Chemotherapy Showed Doubling of Time Without Cancer Progression In Phase III Trial of First-Line Metastatic Breast Cancer Patients

ORLANDO, Fla., May 13 /PRNewswire-FirstCall/ -- Genentech, Inc. and Roche (SWX Zurich) today announced that a Phase III study (E2100) of Avastin(TM) (bevacizumab) plus paclitaxel chemotherapy in first- line metastatic breast cancer met its primary efficacy endpoint of improving progression-free survival (PFS), compared to chemotherapy alone. Results from an interim analysis of this study showed that patients receiving Avastin plus paclitaxel doubled the duration of surviving without cancer progression compared to paclitaxel alone (or a hazard ratio of 0.50, which is equivalent to a 50 percent reduction in the risk of cancer progression). Median progression-free survival was 11 months for patients treated with Avastin plus chemotherapy, compared to six months for patients treated with chemotherapy alone. At this interim analysis, a 49 percent improvement in the secondary endpoint of overall survival (or a hazard ratio of 0.67, which is the equivalent of a 33 percent reduction in the risk of death) was observed. Survival data continue to mature. In patients with measurable disease, the overall response rate was 28 percent (93/330) in the Avastin plus chemotherapy arm, a 100 percent increase over the 14 percent (45/316) observed in the chemotherapy alone arm.

"This is the first successful study to show that the scientific approach of attacking a tumor's blood supply by inhibiting angiogenesis can result in improved outcomes for women with first-line metastatic breast cancer, and the study is particularly important given the magnitude of the improvement seen in progression-free survival, the study's primary endpoint," said Kathy D. Miller, M.D., of Indiana University and principal investigator for the study. These data were featured in a press briefing at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO). More detailed data from the study will be presented to meeting attendees by Dr. Miller during a scientific symposium ("Advances in Monoclonal Antibodies for Breast Cancer" -- Monday, May 16, 1:15 p.m. EDT).

A preliminary assessment of safety showed that Grade 3/4 adverse events that occurred more often in the Avastin arm included neuropathy, hypertension and proteinuria. Neuropathy, which is known to be associated with duration of paclitaxel therapy, occurred in 21 percent of patients in the Avastin plus chemotherapy arm and in 14 percent of patients in the chemotherapy alone arm. Hypertension occurred in 13 percent of patients treated with Avastin plus chemotherapy and in no patients who received chemotherapy alone. Proteinuria occurred in 2 percent of patients in the Avastin plus chemotherapy arm compared to no patients in the chemotherapy alone arm. One patient in the Avastin plus chemotherapy arm developed symptomatic congestive heart failure (CHF). Additional adverse events were similar between the two treatment arms. Serious bleeding and blood clots were rare in this study.

"The results from this study are an important advance in the potential treatment of breast cancer," said Hal Barron, M.D., Genentech's senior vice president, development, and chief medical officer. "The data from this trial showed that Avastin had a clinically important improvement in overall survival, the study's secondary endpoint, which is exciting given that this improvement was observed at an early interim analysis. 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 metastatic breast cancer 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, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG). This Phase III study was a randomized, controlled, multicenter trial that enrolled 722 women with previously untreated metastatic breast cancer. The patients enrolled in this trial were randomized to receive treatment with paclitaxel with or without Avastin. Patients with HER2-positive metastatic breast cancer were not enrolled in the study unless they had received prior treatment with Herceptin(R) (Trastuzumab) or were unable to receive treatment with Herceptin. Patients who had received adjuvant paclitaxel within the previous 12 months and patients with a prior history of blood clots or who were receiving blood thinners were also excluded from the study.

About 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 infrequent, and included 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 Breast Cancer

According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. In the United States, breast cancer is the most prevalent form of cancer among women in the United States and a woman is diagnosed with breast cancer every three minutes.

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(R) (Rituximab), Herceptin(R) (Trastuzumab), Avastin(TM) (bevacizumab) and Tarceva(TM) (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

Within the last five years the Roche Group including its partners Genentech in the US and Chugai in Japan has become the world's leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit in different major tumour indications: Xeloda and Herceptin in advanced stage breast cancer, MabThera in non-Hodgkin's lymphoma, and Avastin in colorectal carcinoma. In the United States Herceptin, MabThera and Avastin are marketed either by Genentech alone or together with Biogen Idec Inc. Outside of the United States, Roche and its Japanese partner Chugai are responsible for the marketing of these drugs.

The Roche oncology portfolio also includes NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcaemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (hairy cell and chronic myeloid leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. The Roche Group's cancer medicines generated sales of more than 3.3 billion Swiss francs in the first half of 2004.

Roche is developing new tests, which 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, we will continue to be the leaders in providing cancer focused treatments and diagnostics.

Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland).

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/.

CONTACT: media, Colleen Wilson, 650-225-7739, or investors, Kathee Littrell, 650-225-1034, or advocacy, Cheya Pope, 650-225-6334, or Roche Media Line, +41 61 688 8888.