Wednesday, Dec 5, 2001
Silver Spring, Maryland -- December 5, 2001 --Genentech, Inc. (NYSE: DNA) announced today that the Oncologic Drugs Advisory Committee (ODAC) to the U.S. Food and Drug Administration (FDA) voted unanimously 16-0 to recommend including new information to physicians using Herceptin® (Trastuzumab) about a gene-detection test called FISH (fluorescence in situ hybridization) (PathVysion™) that identifies women with metastatic breast cancer who could benefit from Herceptin therapy. Herceptin is FDA approved for the treatment of patients both as first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy.
"We are pleased with the outcome of today's panel," said Susan D. Hellmann, M.D., MPH, Genentech's executive vice president, Development and Product Operations and chief medical officer. "We will work closely with the FDA to determine the appropriate information and context toward approval of inclusion of PathVysion into the Herceptin package insert."
Herceptin is a targeted monoclonal antibody treatment for women with HER2 positive metastatic breast cancer, an especially aggressive form of the disease. Special testing is required to discover which women are HER2 positive and candidates for treatment with Herceptin.
"The power of personalized medicine is being able to identify -- in advance of treatment -- those patients most likely to respond to a particular therapy," said Robert Mass, M.D., associate director of Oncology at Genentech, who presented the FISH research to the committee. "The importance of identifying appropriate patients is highlighted by the fact that Herceptin with chemotherapy demonstrated an increased survival benefit compared to chemotherapy alone for HER2 positive metastatic breast cancer patients in our pivotal trial. FISH testing can be an appropriate method that allows physicians to screen tumors with precision and helps ensure that each patient receives the treatment best-suited for their particular disease."
About FISHFISH is a diagnostic test used to determine the number of HER2 genes in a patient's breast cancer cells. Women whose cancer cells contain too many copies of the HER2 gene are candidates for Herceptin therapy. Herceptin is designed specifically to block the cancerous growth-promoting products of the excessive number of HER2 genes. FISH testing measures the number of genes in each cell, using fluorescent dye so the HER2 genes can be visualized and counted with a special microscope. More than the normal two HER2 genes per cell are present in HER2 positive breast cancer.
About the Research Presented to ODAC
The research that led to the committee's recommendation for approval included a study involving tissue samples from metastatic breast cancer patients. Investigators compared the results of the gene-based FISH test, PathVysion, marketed by Vysis Inc., with the manual HER2 immunohistochemical (IHC) protein test used in the Herceptin pivotal study.
Data from this prospectively-designed analysis show that gene tests with FISH are reliable, accurate and have a high rate of concordance or agreement (88%) with the protein test used in Herceptin pivotal studies to diagnose HER2-positive breast cancer.
A second analysis presented today was an exploratory retrospective evaluation of FISH as a predictor of clinical benefit with Herceptin. Endpoints of response rate, time to disease progression and survival were analyzed and provided additional support for the use of FISH in selecting Herceptin candidates.
About Breast Cancer and HER2 Positive Breast Cancer
Approximately 1.6 million U.S. women have been diagnosed with breast cancer. The American Cancer Society says approximately 180,000 new cases are diagnosed each year. Genentech estimates there are approximately 164,000 women alive with metastatic disease. Average survival is 18 to 24 months.
Women with HER2-positive tumors have a poorer prognosis, shorter time to disease progression with treatment, increased relapse rates, shortened survival time and disease that is not as responsive to standard therapies, including certain chemotherapy regimens.
Herceptin received 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 has shown an important survival benefit when used in combination with chemotherapy. Herceptin is marketed in the United States by Genentech and internationally by F. Hoffmann-LaRoche.
Herceptin generally is well-tolerated. Overall, the most common adverse events in the pivotal trial were fever, hematologic toxicity and cardiac dysfunction. Infusion-associated signs and symptoms were observed but did not require antibody discontinuation. In the post-marketing setting, rare serious and fatal infusion-related events have occurred. Most patients who experienced the more serious and fatal infusion-related events had pre-existing pulmonary compromise and advanced malignancies.
The most serious adverse event in the pivotal trial was cardiac dysfunction (NYHA Grade I-IV), which occurred more frequently when Herceptin was administered with anthracycline and cyclophoshamide (AC, 27 percent) compared with AC alone (8 percent), or with Herceptin plus paclitaxel (13 percent) compared to paclitaxel alone (1 percent). Although the NYHA Grade III/IV toxicity, which occurred in a smaller percentage of patients, was potentially severe and/or life threatening, signs and symptoms improved in 75 percent of patients and none of the patients receiving paclitaxel had persistent Grade III/IV cardiac dysfunction with medical management.
Genentech, Inc., is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fifteen of the currently approved products of biotechnology stem from or are based on Genentech science. Genentech markets ten 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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