Wednesday, Sep 2, 1998

FDA Advisory Committee Recommends Approval of First Monoclonal Antibody for Metastatic Breast Cancer

New Biologic Approach May Help Women with HER2 Protein Overexpression Associated with Aggressive Disease

South San Francisco, Calif. -- September 2, 1998 --

Genentech, Inc. (NYSE: GNE) today announced that Herceptin® (Trastuzumab), a humanized monoclonal antibody, was recommended unanimously (11 to 0) for approval as a single agent in second and third line therapy and in combination with paclitaxel in first line therapy for metastatic breast cancer by the Oncologic Drugs Advisory Committee (ODAC) to the U.S. Food and Drug Administration (FDA). The panel also recommended by a vote of 9 to 2 that the benefit did not outweigh the risks for patients treated concurrently with Herceptin and anthracycline. Ongoing discussions between the FDA and Genentech will address the outcome of this issue. The decision was based on results from clinical testing using Herceptin alone or in combination with chemotherapy.

Herceptin, Genentech's humanized HER2 antibody to the HER2 protein, is a new, targeted approach developed for the treatment of metastatic breast cancer. The proposed use of Herceptin is for the 25 to 30 percent of women with this disease who have tumors that produce excessive amounts of, or overexpress, HER2. HER2 overexpression is associated with more aggressive disease and shortened survival in retrospective studies. Overexpression can be determined by a test performed on a new or stored specimen of tumor tissue.

"The panel's favorable vote is a significant step towards FDA approval and represents a major milestone in the fight against breast cancer," said Susan D. Hellmann, M.D., M.P.H., Genentech's senior vice president, development and chief medical officer. "For the first time, we now have a product engineered to target an underlying genetic defect that produces cancer - in this case, HER2 overexpression."

If approved by the FDA, Herceptin will be the first humanized monoclonal antibody for the treatment of HER2 overexpressing metastatic breast cancer and the second U.S. approval in this new class of biotherapeutic cancer drugs. The first was Rituxan™ (Rituximab), developed by Genentech and its partner IDEC Pharmaceuticals Corporation, approved in November 1997.

Although the FDA is not bound by the decisions of the advisory committee, as a part of its priority review, the FDA is expected to make a decision on Herceptin approval (designated as a Fast Track Product) by November 1998.

Clinical Trial Results

Herceptin, in combination with chemotherapy in a large randomized controlled trial (469 patients), was shown to produce a favorable clinical outcome, improving overall response rates from 28 percent in women treated with chemotherapy alone to 43 percent with Herceptin added, a 53 percent increase. The median time to disease progression increased from 4.5 months in chemotherapy alone to 7.3 months in the Herceptin-plus-chemotherapy group.

Median time to disease progression is measured from the time the patients are enrolled in the clinical trial until the time that an increase in tumor size or the appearance of a new tumor mass is assessed.

The most improved clinical benefit was seen in patients who received Herceptin plus the agent paclitaxel. In the Herceptin-plus-paclitaxel group, 36 percent (33 out of 92) of women had a tumor response, compared to 15 percent (14 out of 96) receiving paclitaxel alone. Median duration of response, which is measured from the time the cancer responds to therapy to the time the cancer begins to spread or grow again, was seven months longer with Herceptin and paclitaxel than it was with paclitaxel alone.

Survival data was obtained on all 469 patients who entered the study. Seventy-eight percent of women treated with Herceptin-plus-chemotherapy were still alive after one year compared to 67 percent of women treated with chemotherapy alone, a relative increase of 16 percent. A survival benefit has rarely been demonstrated in previous metastatic breast cancer studies. With the data collected to date, there is not any difference in median survival.

In a trial of 222 women, Herceptin used alone, 14 percent (31 out of 222) of women who had failed one or two prior chemotherapy regimens had objective tumor responses with tumor shrinkage of 50 percent or greater. Tumor response to Herceptin was also shown to be durable with a median duration of response of 9 months. Median survival in this single-arm study was 13 months.

Overall, Herceptin was generally well tolerated in both clinical trials. There were mild infusion-associated symptoms in about 40 percent of patients, such as chills and fever, primarily with the first infusion. In women taking Herceptin alone, the commonly observed side effects associated with chemotherapy were not observed, such as hair loss and destruction of immune system cells. Herceptin use was associated with diarrhea, low white blood cell count and infections.

An increased risk of cardiac dysfunction was observed in approximately one fourth of women receiving Herceptin combined with anthracyclines compared to women receiving anthracyclines alone. The percent of women with cardiac dysfunction in the Herceptin-plus-anthracycline group was 28 percent (41 out of 143) and 7 percent (10 out of 135) for anthracyclines alone. The percent of women with cardiac dysfunction in the Herceptin-plus-paclitaxel group was 11 percent (10 out of 91) and 1 percent (1 out of 95) for paclitaxel alone. In the trial of patients treated with Herceptin alone the incidence was 7 percent (10 out of 213). This side effect was severe and even fatal in some cases but could be effectively controlled with standard cardiac medications in many patients.

Herceptin is a humanized monoclonal antibody that was developed to target HER2 overexpressing breast cancer cells. The antibody specifically binds to HER2, and in laboratory experiments, directly inhibits tumor cell growth.

Routine testing of the tumors from women with metastatic breast cancer will be critical for identification of women with tumors that overexpress HER2 and who could potentially benefit from treatment with Herceptin. There are a number of options available for HER2 testing (at the time of biopsy or using stored tumor tissue obtained during biopsy or surgery). The immunohistochemistry diagnostic test that will be indicated for selecting women with HER2 overexpressing tumors who may be eligible for Herceptin treatment is currently under review by the FDA.

Approximately 1.6 million women have been diagnosed with breast cancer in the United States. 180,000 new cases are diagnosed in any given year, according to the American Cancer Society. Genentech estimates there are approximately 164,000 women with metastatic breast cancer. Of these women, 25 to 30 percent have tumors that overexpress HER2 and may potentially be candidates for this therapy.

Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Eleven of the currently marketed biotechnology products stem from Genentech science, six of which Genentech markets directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange and the Pacific Exchange under the symbol GNE.

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