HHS NEWS

P98-27                        FOOD AND DRUG ADMINISTRATION
FOR IMMEDIATE RELEASE         Lenore Gelb:       301-827-6242
September 25, 1998            
                              Consumer Inquires: 800-532-4440

NEW MONOCLONAL ANTIBODY APPROVED
FOR ADVANCED BREAST CANCER

Herceptin is a monoclonal antibody bioengineered from part of a mouse antibody which is altered to closely resemble a human antibody. It binds to a protein called HER2 which is found on the surface of some normal cells and plays a role in regulating cell growth. In laboratory experiments, Herceptin inhibited tumor cell growth by this binding action. In the case of metastatic breast cancer cells, approximately 30% of tumors produce excess amounts of HER2. Only patients who have tumors with this characteristic have been studied and shown to benefit from the new, targeted approach using Herceptin.

Approximately 1.6 million women have been diagnosed with breast cancer in the United States with 180,000 new cases diagnosed each year, according to the American Cancer Society. When breast cancer tumors produce excess amounts of the HER2 protein, it appears that the cancer may be more aggressive.

"We now have a new weapon in our fight against breast cancer," said HHS Secretary Donna E. Shalala. "For certain women with advanced disease, this product can mean new hope."

"As an oncologist myself, I know nothing is more important than giving patients and their doctors new ways to fight serious and life-threatening illnesses," said FDA Acting Commissioner Michael A. Friedman, M.D. "The increasing use of biological products such as Herceptin to treat the underlying causes of diseases is an exciting development in medicine. FDA will continue to make the review of products for serious and life-threatening diseases one of our highest agency priorities."

The benefits of Herceptin were shown in two clinical trials. In a randomized, controlled clinical trial, 469 patients with metastatic disease who over-expressed HER2 were assigned to receive chemotherapy alone or chemotherapy in combination with Herceptin. As a group, the women who received chemotherapy plus Herceptin had less rapid tumor growth, more tumors were reduced 50% or more in size, and one-year survival rates were higher.

Specifically, the median time to disease progression was 7.2 months for those receiving Herceptin and chemotherapy and 4.5 months for patients receiving chemotherapy alone. The overall tumor response was 44% in the Herceptin group and 29% in the chemotherapy alone group. The one-year survival rate for the Herceptin combination treatment was 79% versus 68% for chemotherapy alone.

In a second clinical trial with 222 patients, Herceptin was found effective when used alone for a group of breast cancer patients who had relapsed following previous chemotherapy for metastatic disease. The tumor response rate was 14% overall, with 3% of patients having their tumors completely disappear. Tumor responses lasted in a range of 6 weeks to 18 months, with a median of 9 months.

In both clinical trials, the patients who responded best to Herceptin had the highest levels of HER2 protein.

Testing of tumors from women with metastatic breast cancer is critical for the identification of the 25-30% of patients who over express HER2 and who can potentially benefit from treatment with Herceptin. A new test to measure HER2 protein in tumors and help identify patients who may benefit from Herceptin treatment was approved today by the FDA's Center for Devices and Radiological Health (CDRH). The new test is called the DAKO HercepTest, manufactured by Dako, a Denmark-based company.

Selection of patients who are most likely to benefit is important because along with the benefit for certain patients also come possible serious risks. The use of Herceptin either alone or in combination with chemotherapy can result in a weakening of the heart muscle which can lead to congestive heart failure. This potentially life-threatening side-effect was most common in patients who received Herceptin in combination with chemotherapy consisting of anthracyclines and cyclophosphamide (AC). Because the benefit is not great enough to overcome this serious risk, Herceptin is not approved to be used with AC.

All patients treated with Herceptin should have their heart function assessed before starting treatment and be closely monitored during treatment. If patients have heart problems, physicians must be extremely cautious in deciding whether the potential benefit is worth this risk.

Other side-effects which were more frequent with Herceptin plus chemotherapy as compared to chemotherapy alone include a reduction of white blood cells (leukopenia), anemia, diarrhea, abdominal pain and infections. Side-effects that occur in about half of the patients during the first infusion with Herceptin include chills, fever, pain, weakness, nausea, vomiting and headache. These were treatable and were much less likely to occur with subsequent infusions.

Herceptin is administered as an intravenous infusion given weekly, according to the package insert. The treatment can be administered in an outpatient setting.

Herceptin is the second monoclonal antibody approved to treat cancer. The first, Rituxan (trade-name), was approved in Nov., 1997, for patients with one type of non-Hodgkin's lymphoma, a cancer of the immune system.

Herceptin is manufactured by Genentech, Inc., San Francisco, Calif. FDA's Center for Biologics Evaluation and Review (CBER) granted fast track and priority review status to Genentech's application for Herceptin and reviewed and approved it in approximately 4.5 months. For further information about the availability of Herceptin, physicians or patients can call the company at 1-888-777-4464.