Friday, Aug 11, 2006
South San Francisco, Calif. -- August 11, 2006 --Genentech, Inc. (NYSE: DNA) today announced that the U.S. Food and Drug Administration (FDA) has notified the company that additional information recently requested during the review of the supplemental Biologics License Application (sBLA) for Herceptin® for the treatment of patients with early stage, HER2-positive breast cancer has been deemed a major amendment. The information requested, additional analyses of previously submitted studies, has already been provided to the agency. In accordance with FDA guidelines, the agency has extended the review period for the sBLA up to an additional 90 days beyond the August 17, 2006 action date. The company submitted the sBLA in February 2006 and it was granted Priority Review.
"We are committed to working with the FDA to complete this review and are confident that we will be able to finalize approval discussions quickly," said Hal Barron, M.D., Genentech senior vice president, Development and chief medical officer.
About the Herceptin Adjuvant sBLA Submission
The sBLA submission is based on a planned joint interim analysis of more than 3,000 patients with early-stage (or cancer that has not spread beyond the breast and the associated lymph nodes), HER2-positive breast cancer enrolled in two Phase III trials. 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), in collaboration with the Cancer And Leukemia Group B, the Eastern Cooperative Oncology Group and the Southwest Oncology Group.
In these randomized, controlled studies, patients received either Herceptin with paclitaxel chemotherapy or paclitaxel chemotherapy alone, following initial treatment with surgery and four cycles of anthracycline and cyclophosphamide (AC). The primary endpoint of the studies was disease free survival. The interim analysis of 3,351 of the 5,635 women enrolled showed that the addition of Herceptin to standard adjuvant therapy significantly reduced the risk of breast cancer recurrence by 52 percent compared to those who received chemotherapy alone (a hazard ratio of 0.48). After three years in the study 13 percent of women treated with Herceptin plus chemotherapy experienced disease recurrence, compared to 25 percent of women treated with chemotherapy alone. A survival analysis conducted after patients had been followed for a median of 24 months 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). Investigators continue follow-up of patients participating in the studies, and data continue to mature.
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. As reported by the cooperative groups, the three-year cumulative incidence of Class III or IV congestive heart failure or death from cardiac causes in the Herceptin arm was 4.1 percent in the NSABP trial and 2.9 percent in the NCCTG trial. Other adverse events reported in both studies included rare cases of interstitial pneumonitis, which occurred at a rate of less than 1 percent.
In August 2005, Genentech issued a letter to healthcare providers informing them of updated cardiotoxicity information related to the use of Herceptin in the adjuvant breast cancer setting obtained from the NSABP study.
About the Herceptin Adjuvant Clinical Trial Program
In addition to the NSABP and NCCTG studies, interim analyses of two additional adjuvant studies announced last year showed that the addition of Herceptin to a chemotherapy regimen increased disease-free survival for women with early-stage HER2-positive breast cancer.
In May 2005, an interim analysis from an adjuvant trial called HERA (HERceptin Adjuvant) conducted internationally by Roche and the Breast International Group (BIG) was reported at the ASCO meeting, and these results were published in the New England Journal of Medicine in October 2005. An international study supported by Sanofi-aventis and Genentech, and conducted by the Breast Cancer International Research Group (BCIRG), also showed that treatment with Herceptin in addition to or following chemotherapy improved disease-free survival. These data were announced in September 2005 and presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2005.
Herceptin is a targeted therapeutic antibody treatment for women with human epidermal growth factor receptor 2 (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 have HER2-positive breast cancer 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 a 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 of HER2-positive metastatic breast cancer patients, Herceptin has shown a survival benefit when used in combination with chemotherapy. In December 2001, Genentech received FDA approval to include, in the product label, data that showed an improved 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. 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, 212,920 women in the United States will be diagnosed with breast cancer in 2006, and 40,970 will die from the disease. Excluding skin cancer, breast cancer is the most common form of cancer among women.
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 conducting 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). For sale outside of the United States, Genentech has licensed Rituxan, Herceptin, and Avastin to Roche, and OSI Pharmaceuticals has licensed Tarceva to Roche.
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. An investigational antibody directed at the HER pathway is currently in Phase II trials. In early development, are a small molecule directed at the hedgehog pathway and an investigational agent targeting apoptosis.
Founded 30 years ago, 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 and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed 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 Herceptin, please call 800-821-8590 or visit http://www.gene.com.
This press release contains a forward-looking statement regarding finalizing approval discussions for our Herceptin sBLA. Such statement is a prediction and involves risks and uncertainties such that the actual result may differ materially. Among other things, finalizing approval discussions for the Herceptin sBLA could be affected by unexpected safety, efficacy or manufacturing issues, need for additional data or clinical studies, additional time requirements for data analyses or decision making, discussions with the FDA, FDA actions or delays or failure to receive FDA approval. Please also refer to Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake, any obligation to update or revise the forward-looking statement in this press release.