FDA Advisory Committee Recommends Approval of First Test to Select Potential Patients for New Biologic Drug for Breast Cancer

Business Wire, Sept 4, 1998

COPENHAGEN, Denmark--(BW HealthWire)--Sept. 4, 1998--DAKO A/S today announced that HercepTest(TM) was recommended unanimously for approval by a joint committee of the Hematology and Pathology Devices Panel and Immunology Devices Panel to the U.S. Food and Drug Administration (FDA) conditional on the company providing clear guidelines on conducting the test.

The new immunohistochemical (IHC) test was designed specifically to identify patients with breast cancer whose tumor tissue produces excessive amounts of (overexpresses) the HER2 protein. This protein is associated with tumor cell growth, aggressive disease and shortened survival. A positive test result will aid in the assessment of patients for whom treatment with Herceptin(R) (Trastuzumab) is being considered. Herceptin, made by Genentech, is an investigational agent targeted specifically against HER2 protein overexpression that, if approved, will be the first monoclonal antibody for treatment of HER2 overexpressing metastatic breast cancer.

On September 2, Herceptin was recommended unanimously for approval by the Oncologic Drugs Advisory Committee (ODAC) to the FDA based on positive results when the new biologic drug was used alone as second or third line therapy or in combination with paclitaxel as the first line therapy for the treatment of patients with metastatic disease who overexpress the HER2 protein. It is estimated that in the United States 25 to 30 percent of approximately 164,000 women diagnosed with metastatic breast cancer overexpress the HER2 protein.

Testing for HER2 protein overexpression should include women diagnosed with metastatic breast cancer and can be carried out on new or stored specimens of tumor tissue, the company advises. Evaluation of a patient's HER2 protein status when added to the results of other tests and the patient's overall condition help oncologists determine the best treatment regimen for each woman. Ultimately, the new IHC test will provide definitive information on whether to consider Herceptin use or not.

DAKO is a leader in immunohistochemical testing for diagnosis of solid tumors and also provides estrogen receptor (ER) and progesterone receptor (PR) antibodies for diagnosis of breast cancer.

"With the panel's favorable vote for HercepTest, we are one step closer to bringing the first commercially available standardized test to physicians that will identify a patient's HER2 protein status and help identify those who may benefit most from Herceptin therapy," said Sven Erik Godtfredsen, DAKO vice president of Corporate Research and Development. "If approved the HercepTest will represent a milestone in DAKO's efforts to bring our global expertise in cancer diagnostics to the marketplace to benefit breast cancer patients. We are particularly excited about being part of an FDA approval process where for the first time a new drug and corresponding diagnostic test are being reviewed at the same time."

HER2 Protein Overexpression vs. HER2 Amplification

Each cell contains two copies of the HER2 protooncogene, which are instrumental in normal cell growth. HER2 gene amplification may result in cells containing an overabundance of the HER2 protein receptor on the cell surface and indicates oncogenic (cancer-generating) activity. The overexpression is associated with tumor growth and subsequent metastasis to other organs. In the Herceptin clinical trials, all patients who qualified for treatment tested positive for HER2 protein overexpression.

Concordance with Herceptin Clinical Trials

During the Herceptin clinical trials, it was determined that a simpler test was needed to identify patients who potentially could benefit from Herceptin. DAKO proposed to the FDA to develop a test that if successful would reach or exceed a concordance level of 75 percent when compared to the immunohistochemical assay applied in the clinical trials for Herceptin. HercepTest exceeded this goal with a concordance of 79 percent that was shown to be reproducible in and between laboratories.

If approved, HercepTest will be used by pathologists or technologists in testing biopsied or surgically removed tissues. The test is based on a polyclonal antibody developed by DAKO for specific detection of the HER2 protein. The antibody is applied to the tissue and its binding is subsequently visualized to indicate the level of presence of antigen in the tissue.

The DAKO test is easy to conduct with relatively few steps and equipment routinely found in pathology laboratories. It requires about three hours to stain specimens of paraffin-embedded tissue that subsequently can be evaluated by the pathologist against a pre-determined scoring system.

HercepTest is a result of an agreement announced in March 1998 between Genentech and DAKO. Under the terms of the agreement, Genentech granted DAKO a license under Genentech patent rights and know-how for development of an IHC kit that potentially could be used to diagnose overexpression of HER2 in breast cancer patients.

DAKO develops, manufactures and sells diagnostic products for immunohistochemistry, flow cytometry, clinical immunochemistry and microbiology. The majority of DAKO products are derived from the company's own research and expertise in antibody and probe technologies. The company has headquarters in Copenhagen, Denmark and subsidiaries in the United States, Japan and all major European countries. The U.S. subsidiaries are located in Boston and Carpinteria, Calif.