Friday, May 13, 2005
South San Francisco, Calif. -- May 13, 2005 --Genentech, Inc. (NYSE: DNA) today announced that data from a joint interim analysis of two Phase III studies of Herceptin® (Trastuzumab) in early-stage breast cancer showed that human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients receiving Herceptin plus chemotherapy had a 52 percent reduction in the risk of disease recurrence compared to those patients who received chemotherapy alone (or a hazard ratio of 0.48). After four years in the study, 15 percent of women treated with Herceptin plus chemotherapy experienced disease recurrence, compared to 33 percent of women treated with chemotherapy alone. Preliminary survival data 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). Survival data continue to mature.
"The reduction in disease recurrence observed in these trials was the largest improvement I've seen in breast cancer clinical research. Herceptin plus chemotherapy can potentially stop or delay early-stage HER2-positive breast cancer from relapsing," said Edith Perez, M.D., professor of medicine at the Mayo Clinic in Jacksonville, Fla., and the lead investigator in one of the two Herceptin trials. "These trials also underscore the importance for every woman diagnosed with breast cancer to receive a HER2 test."
A preliminary safety analysis showed that adverse events in these studies were consistent with those seen in previous Herceptin clinical trials. 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. Patients in these studies will continue to be followed for any additional side effects.
In these studies, women with early-stage (or cancer that has not spread beyond the breast and the associated lymph nodes) HER2-positive breast cancer received Herceptin plus chemotherapy or chemotherapy alone following initial treatment with surgery and anthracycline and cyclophosphamide (AC). HER2-positive breast cancer is an especially aggressive form of the disease that affects approximately 25 percent of women with breast cancer.
These data were featured in a press briefing at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO). More detailed data from the study will be presented to meeting attendees by Edward Romond, M.D., of the University of Kentucky during a scientific symposium ("Advances in Monoclonal Antibodies for Breast Cancer" - Monday, May 16, 1:15 p.m. EDT).
"These trials are significant because we may be able to treat HER2-positive patients in the earlier stages of their breast cancer, and prevent or delay development of metastatic disease. We're also excited about the improvements seen in the adjuvant setting, since patient outcomes are measured in years rather than months," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech's president, product development. "We would like to thank our collaborators at NCI, NSABP and NCCTG for their work on this study, as well as the many patients and their families who participated in the trial, for their important role in identifying a potential new treatment option for women with HER2-positive breast cancer."
Based on the strength of this interim joint analysis, Genentech will work with the cooperative groups to prepare these data for discussion with the U.S. Food and Drug Administration (FDA) about filing a supplemental Biologics License Application (sBLA) for Herceptin in the adjuvant setting.
About the Study Designs
The National Surgical Adjuvant Breast and Bowel Project (NSABP) study began enrollment in March 2000 and 2,085 patients have participated in the trial to date. The North Central Cancer Treatment Group (NCCTG) study enrolled its first patient in June 2000 and 3,406 patients have participated to date. Both studies are supported by the National Cancer Institute. The joint interim analysis was based on data from 3,351 patients. Each of the studies was a randomized, controlled trial that evaluated the combination of anthracycline and cyclophosphamide (AC) followed by paclitaxel chemotherapy, with or without Herceptin, using different treatment schedules of paclitaxel in women with HER2-positive breast cancer.
About the Herceptin Adjuvant Clinical Trial Program
In addition to the NSABP and NCCTG adjuvant studies, Roche and Breast International Group (BIG) announced in April 2005 that the interim analysis of HERA (HERceptin Adjuvant), a large-scale, 39-country, Phase III study with a wide range of chemotherapy regimens, showed that the addition of Herceptin increased disease-free survival for women with early-stage HER2-positive breast cancer.
Enrollment in the HERA trial began in December 2001, and nearly 5,100 patients have been enrolled at 480 sites in 39 countries worldwide. The interim analysis compared 12 months of Herceptin versus observation and did not include a comparison of 24 months of Herceptin versus observation. These data will become available as the study matures.
The HERA study has an external Independent Data Monitoring Committee (IDMC) that regularly reviews safety data. No safety concerns have been raised by the IDMC to date. Patients in this study will continue to be followed for any side effects.
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 25 percent of women with breast cancer. Special testing is required to identify women who are HER2-positive and who may be candidates for treatment with Herceptin.
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 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, in Japan by Chugai, and outside of the United States and Japan by Roche.
In clinical trials, Herceptin has shown a survival benefit when used in combination with paclitaxel 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.
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 febrile neutropenia was 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 211,000 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. In the United States, breast cancer is the most prevalent form of cancer among women and a woman is diagnosed with breast cancer 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://ww.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://ww.gene.com.