Healthcare Industry News:  HER2 

Biopharmaceuticals Oncology FDA

 News Release - February 15, 2006

Genentech Submits Supplemental Biologics License Application for Adjuvant Herceptin(R) in Early-Stage HER2-Positive Breast Cancer

Filing Based on Data from More than 3,000 Women in Two Phase III Trials

SOUTH SAN FRANCISCO, Calif., Feb. 15 (HSMN NewsFeed) -- Genentech, Inc. (NYSE: DNA ) announced today that the company completed the submission of a supplemental Biologics License Application (sBLA) with the U.S. Food and Drug Administration (FDA) for use of HerceptinŽ (Trastuzumab) to treat early-stage, HER2-positive breast cancer. Genentech has requested a Priority Review designation from the FDA, which if granted, requires the FDA to take action on the application within six months.

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.

The analysis showed that the addition of Herceptin to standard adjuvant therapy significantly reduced the risk of breast cancer recurrence, the primary endpoint of the studies, by 52 percent in women with early-stage, HER2-positive breast cancer, compared to those patients who received standard adjuvant therapy alone (or 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.

The primary endpoint (disease-free survival) results demonstrated that the benefit of adding Herceptin to chemotherapy in all clinically important patient subgroups studied, including age, hormone receptor status, tumor size, number of positive nodes, and the cooperative group protocol by which each patient was treated, was consistent with the benefit seen in the overall population.

"The two U.S. cooperative groups and the lead investigators made the joint analysis of these Phase III results possible. Their efforts involved an unprecedented level of collaboration, which ultimately allowed for these important results to be available for physicians and patients much earlier than had the trials continued on separate paths," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech's president, product development.

About the Studies Included in the Filing

The NSABP study began enrollment in March 2000 and enrolled 2,130 patients. The NCCTG study enrolled its first patient in June 2000 and enrolled 3,505 patients. In these randomized, controlled studies, women with early-stage HER2-positive breast cancer received either Herceptin with paclitaxel chemotherapy or paclitaxel chemotherapy alone, following initial treatment with surgery and four cycles of anthracycline and cyclophosphamide (AC). The joint interim analysis was based on data from 3,351 patients of the 5,635 women enrolled in both studies. These results were first presented at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO) in May 2005 and subsequently published in The New England Journal of Medicine (NEJM) in October 2005.

Safety Analysis

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 of last year, 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.

About Herceptin

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, an estimated 211,240 women were diagnosed with breast cancer and approximately 40,000 women died 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 RituxanŽ (Rituximab), HerceptinŽ (Trastuzumab), AvastinŽ (bevacizumab), and TarcevaŽ (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 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 and a protein targeting apoptosis.

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, California and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit

For full prescribing information, including Boxed Warnings for Herceptin, please call 800-821-8590 or visit

Source: Genentech

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