Tuesday, May 23, 2000

Single Agent Herceptin Demonstrates 26 Percent Response Rate as Front-Line Metastatic Breast Cancer Therapy in Phase II Trial

New Orleans -- May 23, 2000 --

Genentech, Inc. (NYSE: DNA) today announced that in preliminary results of an investigational Phase II study evaluating Herceptin® (Trastuzumab) as a single agent in women with previously untreated HER2-positive metastatic breast cancer, Herceptin demonstrated a 26 percent (30/114 patients) overall response rate. Data from this study were presented today by Charles Vogel, M.D., Aventura Comprehensive Cancer Center, at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).

Additionally, the company announced results from a retrospective study between two HER2 testing methods presented by Robert Mass, M.D., clinical scientist at Genentech. Preliminary data shows that measuring HER2 gene amplification by Florescence In Situ Hybridization (FISH), a DNA-based method different from the FDA-approved immunohistochemisty (IHC) method, may provide an alternative for identifying women with HER2-positive metastatic breast cancer that have the potential to respond to Herceptin therapy.

Genentech plans to submit the data to the U.S. Food and Drug Administration (FDA) in the near future.

"Herceptin is the first example of an approved targeted therapy for cancer that is based on understanding the role that a specific gene plays in tumor growth," said Susan D. Hellmann, M.D., M.P.H., executive vice president of Development and Product Operations and chief medical officer. "Herceptin in combination with chemotherapy has demonstrated a significant survival benefit in a patient population with a very aggressive form of metastatic breast cancer. The retrospective data on HER2 testing will provide oncologists with new information that may make Herceptin an even more targeted and effective therapy."

Phase II Study Evaluating Single Agent Herceptin in HER2-Positive Front-Line Metastatic Breast Cancer

In this Phase II study, the overall response rate of the entire trial group was 26 percent (30/114 patients). All responses were seen in patients who overexpressed HER2 at the highest 3+ level by immunohistochemistry (IHC) testing. Overall survival was 24.4 months.

"This investigational study shows that Herceptin is active when given alone as front-line therapy for women with HER2-positive metastatic breast cancer," said Dr. Vogel, the principal investigator.

In the study, 114 women previously untreated for HER2-positive metastatic breast cancer were randomized into two treatment groups: one group received Herceptin alone at the approved regimen of 4 mg/kg IV loading dose followed by a 2 mg/kg maintenance dose administered weekly until disease progression, and the other group received a higher dose regimen consisting of an 8 mg/kg loading dose followed by a 4 mg/kg maintenance dose of Herceptin weekly until disease progression.

Results for the primary and secondary endpoints of this study (response rate, time to disease progression and survival) were all similar in both the standard and high dose groups.

In this study, Herceptin alone appeared to be generally well tolerated with some patients experiencing infusion-related side effects including chills (25%), asthenia (23%) fever (22%) pain (18%), and nausea (14%) most often with the first infusion. Two of the 114 patients developed cardiac dysfunction, both of whom had significant pre-existing cardiac disease.

HER2 Gene Amplification as Detected by FISH (Fluorescence In Situ Hybridization)

In the retrospective study, Mass et. al. analyzed the concordance between the clinical trial immunohistochemistry (IHC) assays used in the pivotal trials of Herceptin to identify HER2 protein overexpressing patients, with HER2 gene amplification measured by the PathVysion® FISH (Fluorescence in situ hybridization) assay, developed by Vysis. The goal of this study was to determine how HER2 gene amplification, measured by FISH, compares to HER2 protein overexpression as measured by IHC in patients enrolled in the pivotal trials.

In this retrospective study, available patient samples (623) from three Herceptin studies were analyzed and randomized in a 1:1 fashion, of which 317 were positive using the IHC method developed for clinical trial purposes for HER2 protein overexpression and 306 were negative for HER2 protein overexpression. Each tumor tissue was then assayed for HER2 gene amplification by FISH (a total of 529 of the 623 samples were evaluable). Amplification was 4.2 percent in the 0+ overexpressing group, 6.7 percent in the 1+ group, 23.9 percent in the 2+ group, and 89.3 percent in the 3+ group.

"While further research, including prospective studies, needs to be conducted, we believe that these data are important for physicians and women with metastatic breast cancer. In identifying HER2 amplification status we can provide an alternative method to determine those who are the most likely to benefit from Herceptin therapy," said Dr. Mass.

Background on Herceptin

Herceptin was approved 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. In the pivotal studies, Herceptin as a single agent demonstrated a 14% (31/222) response rate and in combination with paclitaxel a 42% (39/92) response rate.

Herceptin was generally well tolerated by the 958 women treated in clinical trials. Overall, the most common adverse events have been chills and fever in approximately 40 percent of patients, primarily with the first infusion. An increased risk of cardiac dysfunction has been observed in women receiving Herceptin and anthracyclines (28%) compared to those receiving anthracyclines alone (7%), as well as those receiving Herceptin and paclitaxel (11%) compared to paclitaxel alone (1%) in the pivotal trials. This side effect can be potentially severe or life-threatening, but in most cases can be managed with medication or through discontinuation of Herceptin infusion. Additionally, in the post-marketing setting, 62 patients of the 25,000 women treated with Herceptin developed rare serious infusion-related adverse events of which 15 were fatal. Most patients who experienced the more serious and fatal infusion-related events had pre-existing pulmonary compromise secondary to advanced malignancy. Genentech has recently addressed this issue in a letter to physicians issued in May 2000.

Approximately 1.6 million women have been diagnosed with breast cancer in the United States. According to the American Cancer Society, approximately 180,000 new cases are diagnosed in any given year. Genentech estimates there are approximately 164,000 women with metastatic breast cancer. Of these women, 25-30 percent have HER2-positive tumors and may be candidates for Herceptin. Routine testing of the tumors from women with metastatic breast cancer is critical for identification of patients with HER2 driven disease and who could potentially benefit from Herceptin therapy.

Genentech, Inc., is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Thirteen of the approved products of biotechnology stem from Genentech science. Genentech markets seven 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.

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