Genentech Announces Preliminary Results From Randomized Phase II Trial of Avastin and Tarceva in Kidney Cancer

SOUTH SAN FRANCISCO, Calif., Oct. 18 /PRNewswire-FirstCall/ -- Genentech, Inc. today announced that the company has performed a preliminary analysis of a randomized Phase II study designed to evaluate the incremental benefit of adding Tarceva(R) (erlotinib) to Avastin(R) (bevacizumab) in metastatic renal cell carcinoma (kidney cancer). This trial measured two co-primary efficacy endpoints, progression-free survival and response rate, and preliminary estimates suggested that the addition of Tarceva to Avastin resulted in progression-free survival and response rates similar to those achieved with Avastin alone. Due to the exploratory nature of the study, these estimates do not provide definitive conclusions with high statistical certainty with respect to differences between the treatments. Genentech will continue to analyze the study results and will submit the data for presentation at an upcoming medical meeting.

"At this time we do not believe further studies of this particular combination in kidney cancer are warranted. However, we remain encouraged by the duration of progression-free survival seen in patients treated with Avastin both in this trial and in previous studies in kidney cancer," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "Combining agents that target different cancer pathways remains an area of active investigation for Genentech and may be a viable alternative to chemotherapy. We will continue to vigorously investigate combinations of targeted therapies in other cancers."

This exploratory Phase II, randomized, double-blind, controlled, multicenter trial enrolled 104 patients with metastatic renal cell carcinoma (RCC). Patients were randomized to receive either Avastin with Tarceva, or Avastin with placebo. Patients received Avastin every two weeks, and either Tarceva or placebo daily. All study participants had metastatic RCC of clear cell histology and had undergone prior nephrectomy (surgical removal of all or part of the kidney). Patients who had previously received systemic therapy for RCC (such as chemotherapy) were not eligible to enroll.

A preliminary assessment of safety showed that adverse events in this study were similar to those observed in previous clinical trials of Avastin in combination with Tarceva, and included diarrhea, rash, nausea/vomiting, hypertension, bleeding, proteinuria and pruritus. More detailed information about adverse events will be available when the data are presented.

About Avastin

Avastin, which is marketed in the U.S. by Genentech and outside of the U.S. by the Roche Group, 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 anti-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, pancreatic, 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 Tarceva

Tarceva, which is marketed in the U.S. by Genentech and OSI Pharmaceuticals and outside of the U.S. by the Roche Group, is a small molecule designed to target the human epidermal growth factor receptor 1 (HER1) pathway, which is one of the factors critical to cell growth in non-small cell lung cancer (NSCLC) and other solid tumors. HER1, also known as EGFR, is a component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. Tarceva is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth. Tarceva is the only HER1/EGFR-targeted therapy proven to significantly prolong survival in second-line NSCLC.

Tarceva was approved by the FDA in November 2004 and is an oral tablet indicated for daily administration for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Results from two earlier large, randomized, placebo-controlled clinical trials in first-line advanced NSCLC patients showed no clinical benefit with concurrent administration of Tarceva with doublet platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is not recommended in that setting.

Additional early-stage trials of Tarceva are being conducted in other solid tumors. In April 2005, OSI submitted a supplemental New Drug Application (sNDA) with the FDA for use of Tarceva plus gemcitabine chemotherapy for the treatment of locally advanced, unresectable or metastatic pancreatic cancer in patients who have not received any previous treatment. For Tarceva full prescribing information, please call 1-877-TARCEVA or visit http://www.tarceva.com/ .

Safety Profile

In the pivotal NSCLC trial, the most common adverse reactions in patients receiving Tarceva were rash and diarrhea. Grade 3/4 rash and diarrhea occurred in 9 and 6 percent of Tarceva-treated patients, respectively. Rash and diarrhea each resulted in discontinuation of 1 percent of Tarceva-treated patients. Dose reduction for rash and diarrhea was needed for 6 and 1 percent of patients, respectively. Historically, there have been infrequent reports of serious interstitial lung disease (ILD), including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumors. In the pivotal trial, severe pulmonary reactions, including potential cases of interstitial lung disease, were infrequent (0.8 percent) and were equally distributed between treatment arms. The overall incidence of ILD in Tarceva-treated patients from all NSCLC studies was approximately 0.6 percent.

About Renal Cell Carcinoma

According to the American Cancer Society, there will be 36,160 new cases of kidney cancer (22,490 in men and 13,670 in women) in the United States in 2005, and about 12,660 people will die from this disease. Renal cell carcinoma is the most common type of kidney cancer, and accounts for more than 90 percent of malignant kidney tumors.

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(R) (bevacizumab) and Tarceva(R) (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/ .

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/ .

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