Monday, Apr 25, 2005
South San Francisco, Calif. -- April 25, 2005 --Genentech, Inc. (NYSE: DNA) today announced that two Phase III trials of Herceptin were stopped early after a preliminary joint interim analysis demonstrated an improvement in the primary endpoint of disease-free survival and in the secondary endpoint of overall survival. The trials compared Herceptin plus chemotherapy to chemotherapy alone as adjuvant therapy following initial treatment with surgery for women with early-stage (or cancer that has not spread beyond the breast and associated lymph nodes) human epidermal growth factor receptor 2 (HER2) positive breast cancer.
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), who conducted this prospectively-designed joint interim analysis following consultation with the FDA. According to the NCI, the cooperative groups will present results from these studies at the American Society of Clinical Oncology (ASCO) annual meeting, May 13-17, 2005.
"The data from these very important Phase III trials suggest for the first time that a therapy that targets women whose tumors have a specific genetic mutation has the potential to reduce the recurrence of disease in early-stage breast cancer patients," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech's president of Product Development. "While further follow-up is 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."
"Conducting this type of joint analysis, which enabled the groups to obtain these important results more than two years earlier than expected is unprecedented and we would like to thank the NSABP, NCCTG, the NCI and the FDA for their extraordinary efforts in combining these studies. We would also like to thank the women who participated in this study for their tremendous courage in making these results possible. Based on the strength of the results, we will work with the cooperative groups to prepare these data for discussion with the FDA about a filing for Herceptin in the adjuvant setting based on this interim analysis," continued Dr. Hellmann.
The NCCTG study enrolled its first patient in June 2000 and has enrolled 3,406 patients to date; the NSABP study began enrollment in March 2000 and has enrolled 2,085 patients to date. The interim analysis was based on information from 3,300 patients. These studies will stop enrolling new patients and the cooperative groups will continue to monitor patients for longer-term data. Each of the studies was a randomized, controlled trial that evaluated the combination of anthracycline and cyclophosphamide (AC) followed by paclitaxel, with or without Herceptin using different treatment schedules of paclitaxel in women with HER2-positive breast cancer.
Adverse events in these studies were consistent with those seen in previous Herceptin clinical trials. Each of these studies has an independent, external Data Monitoring Committee (DMC) that reviewed data from the studies, including cardiac safety data. The DMCs monitored safety data on a regular basis and there were three to four percent more cases of serious or life-threatening (and in rare cases, fatal) cardiac events, most commonly congestive heart failure (weakening of the heart muscle) in patients receiving the combination of Herceptin plus chemotherapy. Patients in these studies will continue to be followed for any additional side effects.
Based on the positive results from four recent Phase III trial analyses in the past five weeks, three of which occurred earlier than anticipated, Genentech will continue to evaluate its short- and long-term product demand and to assess its manufacturing plans and capacity to meet expected demand. The company expects to provide further information on manufacturing at the time of Q2 earnings results.
About the Herceptin Adjuvant Clinical Trial Program
Based on positive data observed when adding Herceptin to chemotherapy in patients with HER2-positive metastatic breast cancer, several cooperative groups are investigating Herceptin in combination with chemotherapy as a potential treatment in early-stage breast cancer. In addition to the NSABP and NCCTG adjuvant studies, two additional international adjuvant trials are underway, evaluating Herceptin with several different chemotherapy regimens, and in total will enroll more than 13,000 women with early-stage, HER2-positive breast cancer. Each study was designed with interim analyses.
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, 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.
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 211,000 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, either alone (Avastin and Herceptin) or with Biogen Idec Inc. (Rituxan) or OSI Pharmaceuticals, Inc. (Tarceva). 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. A therapeutic antibody directed at the HER pathway is currently in Phase II trials and 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. 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.
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 www.gene.com.