Wednesday, Oct 19, 2005

Pivotal Herceptin Data in the New England Journal of Medicine Showed Significant Improvement in Disease-Free Survival in Early-Stage HER2-Positive Breast Cancer

Interim Analysis of Two Phase III Trials Showed That Adding Herceptin to Chemotherapy Reduced the Risk of Breast Cancer Recurrence by 52 Percent

San Francisco, Calif. -- October 19, 2005 --

Genentech, Inc. (NYSE: DNA) today announced that The New England Journal of Medicine published data from a joint interim analysis of two pivotal Phase III trials of Herceptin® (trastuzumab) plus chemotherapy. The analysis showed that the addition of Herceptin significantly reduced the risk of breast cancer recurrence by 52 percent in women with early-stage, operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer, compared to those patients who received chemotherapy alone (or a hazard ratio of 0.48). After four years of study follow-up, 15 percent of women treated with Herceptin plus chemotherapy experienced disease recurrence, compared to 33 percent of women treated with chemotherapy alone. HER2-positive breast cancer is an especially aggressive form of the disease that affects approximately 25 percent of women with breast cancer.

These data are from a planned interim analysis of more than 3,000 patients, and were first presented at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO) in May 2005. The two studies were sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG).

"The results of these studies represent in quantitative terms the largest improvement in outcome for any group of women with breast cancer in 25 years," said Edward H. Romond, M.D., Associate Professor of Medicine, Division of Hematology/Oncology at the University of Kentucky. "If these early findings continue to hold up, it may mean that the prognosis for women with one of the most worrisome types of breast cancer could change from poor to good."

Subgroups that showed improvement in the primary endpoint of disease-free survival included age, hormone receptor status, tumor size, number of positive nodes, and the cooperative group protocol by which each patient was treated.

"While additional years of follow-up are necessary, the results of this joint interim analysis suggest that adjuvant therapy with Herceptin plus chemotherapy for women with early-stage HER2-positive breast cancer may increase the chance of long-term survival," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech's president, product development. "The joint analysis data will become the basis for a supplemental Biologics License Application (sBLA) for Herceptin in the adjuvant setting with the U.S. Food and Drug Administration (FDA)."

A survival analysis conducted after patients had been followed for a median of 24 months showed a 49 percent improvement in overall survival (or a hazard ratio of 0.67, which is equivalent to a 33 percent reduction in the risk of death). Investigators continue follow-up of patients participating in the study and data continue to mature.

About the Studies Included in the Joint Analysis
The National Surgical Adjuvant Breast and Bowel Project (NSABP) study began enrollment in March 2000 and 2,130 patients were enrolled. The North Central Cancer Treatment Group (NCCTG) study enrolled its first patient in June 2000 and 3,505 patients were enrolled. The joint interim analysis was based on data from 3,351 patients.

In these randomized, controlled studies, women with early-stage (or cancer that has not spread beyond the breast and the associated lymph nodes) HER2-positive breast cancer received either Herceptin with paclitaxel chemotherapy or paclitaxel chemotherapy alone, following initial treatment with surgery and anthracycline and cyclophosphamide (AC).

Safety Analysis
A preliminary safety analysis showed that adverse events in these studies were consistent with those seen in previous clinical trials combining Herceptin with chemotherapy. Each study had an independent external Data Monitoring Committee (DMC) that reviewed data from the studies, including cardiac safety data on a regular basis. According to the investigators, serious or life-threatening (and in rare cases, fatal) cardiac events, most commonly congestive heart failure (weakening of the heart muscle) occurred approximately 3 to 4 percent more often in the Herceptin plus chemotherapy arms than in the chemotherapy alone arms. In the Herceptin arm, the three-year cumulative incidence of Class III or IV congestive heart failure or death from cardiac causes was 4.1 percent in the NSABP trial and 2.9 percent in the NCCTG trial.

About the Herceptin Adjuvant Clinical Trial Program
In addition to the NSABP and NCCTG studies reported in The New England Journal of Medicine, interim analyses of two additional adjuvant studies announced earlier this year showed that the addition of Herceptin to a chemotherapy regimen increased disease-free survival for women with early-stage HER2-positive breast cancer.

Also in May, an interim analysis from an adjuvant trial called HERA (HERceptin Adjuvant) conducted internationally by Roche and the Breast International Group (BIG) was reported at the ASCO meeting and these results are also published in the current issue of The New England Journal of Medicine. In September, another international study supported by Sanofi-aventis and Genentech, and conducted by the Breast Cancer International Research Group (BCIRG), also showed that treatment with Herceptin in addition to or following chemotherapy improved disease-free survival.

About Herceptin
Herceptin is a targeted therapeutic antibody treatment for women with HER2-positive metastatic breast cancer, an especially aggressive form of the disease that affects approximately one-fourth of women with breast cancer. Special testing is required to identify women who are HER2-positive and candidates for treatment with Herceptin.

Herceptin received U.S. Food and Drug Administration (FDA) approval in September 1998 for use in women with metastatic breast cancer who have tumors that overexpress the HER2 protein. It is indicated for treatment of patients both as first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy. Herceptin is marketed in the United States by Genentech, in Japan by Chugai, and internationally by Roche.

In clinical trials, Herceptin has shown a survival benefit when used in combination with chemotherapy. In December 2001, Genentech received FDA approval to include data that showed a 24 percent increase in median overall survival for women with HER2-positive metastatic breast cancer treated initially with Herceptin and chemotherapy compared to chemotherapy alone (median 25.1 months compared to 20.3 months).

Herceptin Safety Profile
Herceptin therapy does involve risks. Serious side effects have occurred in patients treated with Herceptin in metastatic breast cancer. Herceptin administration can result in the development of ventricular dysfunction and cardiac failure. Severe hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events have been infrequently reported. Rarely, these were fatal.

Recently, Genentech issued a letter to healthcare providers explaining the cardiac monitoring guidelines under which the two U.S. cooperative group trials of Herceptin in the adjuvant setting were conducted.

Serious reactions were treated by discontinuing Herceptin and administering supportive therapy. In clinical trials, the incidence and severity of cardiac dysfunction was highest in patients receiving Herceptin with anthracycline and cyclophosphamide (AC). Most patients responded to medical therapy, including discontinuation of Herceptin. However, some patients were successfully managed while continuing Herceptin therapy. Patients receiving Herceptin should be monitored for deteriorating cardiac function.

In clinical trials, approximately 40 percent of patients experienced symptoms such as chills and fever during the first infusion. These and other symptoms, including nausea, vomiting, and pain, occurred infrequently with subsequent infusions. In clinical trials, the incidence of moderate to severe neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those receiving chemotherapy alone. There was an increased incidence of anemia leukopenia, diarrhea, and infection when Herceptin was used in combination with chemotherapy.

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. Breast cancer is the most common cause of cancer among women in the United States and a woman is diagnosed with breast cancer in the United States 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® (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.

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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.