Monday, Jun 7, 2004

Key Herceptin Data Presented at American Society of Clinical Oncology Meeting

Pivotal Trial Analysis Shows Patients Achieve Clinical Benefit With Herceptin Regardless of Tumor Response

New Orleans -- June 7, 2004 --

Genentech, Inc. (NYSE: DNA) today announced updated results from a Phase III study evaluating Herceptin® (Trastuzumab) in combination with paclitaxel and carboplatin, as well as a retrospective analysis of the pivotal Phase III Herceptin study, in women with HER2 (human epidermal growth factor receptor2)-positive metastatic breast cancer.

In addition to these studies, data from more than 50 studies were presented evaluating Herceptin-based treatment regimens in a variety of settings and disease stages at the 40th annual meeting of the American Society of Clinical Oncology (ASCO).

Trend of Overall Improved Survival in HER2-positive Metastatic Breast Cancer Patients Treated With Herceptin, Paclitaxel and Carboplatin Combination (Abstract #573)
A randomized multicenter Phase III trial, updated by Nicholas Robert, M.D., of Inova Fairfax Hospital, Fairfax, Va., evaluated the efficacy and safety of the combination of Herceptin, paclitaxel and carboplatin compared to Herceptin and paclitaxel in women with HER2-positive metastatic breast cancer. Patients who overexpressed HER2 at the 2+ or 3+ level by immunohistochemistry (IHC) were eligible for the study. The study evaluated 188 patients who received either Herceptin/paclitaxel/carboplatin (n=93) or Herceptin/paclitaxel alone (n=95). As previously reported, patients receiving Herceptin/paclitaxel/carboplatin had an overall response rate (ORR), the primary endpoint, of 52 percent compared to 36 percent for patients receiving Herceptin/paclitaxel. Additionally, median time to disease progression (TTP) was 10.7 months for the Herceptin/paclitaxel/carboplatin arm, compared to seven months for patients receiving Herceptin/paclitaxel, respectively.

A trend toward improvement in overall survival was observed in patients receiving Herceptin/paclitaxel/carboplatin compared to those patients receiving Herceptin/paclitaxel -- an increase to 36 months from 32 months. Additionally, at 48 months, 40 percent of patients who received Herceptin/paclitaxel/carboplatin were alive, compared to 31 percent of patients who received Herceptin/paclitaxel.

In this study, patients whose tumors were HER2 3+ and received Herceptin/paclitaxel/carboplatin (n=62) had a median TTP of 14.0 months compared to 7.1 months for patients treated with Herceptin/paclitaxel (n=63). In this subset of patients, overall survival and 48-month survival was 42 months and 41 percent for patients treated with Herceptin/paclitaxel/carboplatin and 29 months and 28 percent for patients treated with Herceptin/paclitaxel, respectively.

Investigators concluded that the adverse events in this trial were consistent with those observed in previous studies with these agents. Grade 3 and 4 neutropenia and thrombocytopenia were more common with Herceptin/paclitaxel/carboplatin, and there was no difference in fever/neutropenia, neuropathy, fatigue or other toxicities between study arms. There were two cases of congestive heart failure in the Herceptin/paclitaxel arm.

Disease Stabilization Among HER2-positive Metastatic Breast Cancer Patients Not Achieving Objective Responses (Abstract #680)
A retrospective analysis, presented by Christina Yeon, M.D., of the University of California at Los Angeles, evaluated the subset of Phase III pivotal trial metastatic breast cancer patients treated with Herceptin plus chemotherapy or chemotherapy alone who did not achieve an objective clinical response (OCR), also known as non-responders. An OCR is defined as a 50 percent or greater reduction in tumor size. The analysis focused on time to disease progression (TTP) and overall survival (OS) as well as the use of immunohistochemistry or fluorescence in situ hybridization (FISH) to determine HER2 status. Among the 277 patients who did not achieve an OCR, the study found that patients who received Herceptin plus chemotherapy had a significantly longer median TTP than patients who received chemotherapy alone (4.1 vs. 2.8 months). Overall survival for HER2-positive non-responders (as determined by FISH testing) was 16.4 months for patients who received Herceptin plus chemotherapy compared to 13.9 months for patients who received chemotherapy alone. This endpoint did not reach statistical significance.

"These data suggest the important role that targeted biologic therapies, such as Herceptin, can play in stabilizing cancer," said Gwen Fyfe, M.D., Genentech's vice president, Clinical Hematology/Oncology. "Response rate, though important, may not always be a complete surrogate for patient benefit. Thus, disease stabilization, as well as ?tumor shrinkage,' are relevant measures of benefit following treatment with biologic therapies."

Herceptin administration can result in the development of ventricular dysfunction and congestive heart failure. Severe hypersensitivity reactions (including anaphylaxis), infusion reactions and pulmonary events have been observed. These events have rarely been fatal.

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 weekly 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 and internationally by Roche.

In clinical trials, Herceptin has shown an important survival benefit when used in combination with doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel. 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
Administration of Herceptin 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. 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.

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. There was an increased incidence of anemia leukopenia, diarrhea, and infection when Herceptin was used in combination with chemotherapy.

About Genentech
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.

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For full prescribing information for Herceptin, including Boxed Warnings, please call 650-225-8681 or visit http://www.gene.com.