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Sanofi-Aventis Release: Interim Analysis Of Phase III Study Shows TAXOTERE(R) (docetaxel)-Based Chemotherapy Regimens Combined With HERCEPTIN(R) (Trastuzumab) Significantly Improved Disease Free Survival In Early-Stage HER2-Positive Breast Cancer

Published: Sep 15, 2005

EDMONTON, Alberta and BRIDGEWATER, N.J., Sept. 15 /PRNewswire/ -- The Breast Cancer International Research Group (BCIRG) and sanofi-aventis announced results today from an interim efficacy analysis of a Phase III trial which shows two TAXOTERE(R)-based chemotherapy regimens in combination with HERCEPTIN(R), monoclonal antibody therapy, significantly improved disease-free survival in women with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

The BCIRG 006 trial compared a standard treatment arm of 4 cycles of doxorubicin and cyclophosphamide followed by TAXOTERE(R) for 6 cycles, (AC-T) to two Herceptin-containing regimens following initial surgery. One arm included the above regimen with one year of HERCEPTIN(R) (AC-TH) and the other was a non-anthracycline regimen of TAXOTERE(R) plus carboplatin plus one year of HERCEPTIN(R) (TCH). In the latter arm, the HERCEPTIN(R) was started concomitantly (TCH) with chemotherapy. Anthracyclines have been considered a key agent in early breast cancer therapy for over 25 years. HER2-positive breast cancer first described in 1987 in women whose tumors contain this alteration have a much more aggressive form of the disease. With the introduction of HERCEPTIN(R), a targeted therapy against HER2-positive breast cancer, it was found that there was a significant increase in cardiotoxicity when anthracycline was used in conjunction with HERCEPTIN(R). The purpose of the BCIRG trial was twofold; first to determine if the introduction of Herceptin in early stage HER2-positive breast cancer significantly improves clinical outcomes and second, to determine if the increased cardiotoxicity seen with HERCEPTIN(R) when used with anthracyclines could be avoided using a novel regimen of TAXOTERE(R) without anthracyclines.

The BCIRG 006 study entered its first patient in March 2001 and has enrolled a total of 3,222 women. The study is now closed to accrual and the BCIRG continues to monitor patients for longer-term analysis. The results of the first interim efficacy analysis are presented today. The study was sponsored by sanofi-aventis, partially supported financially by Genentech, and conducted by the BCIRG.

This study has an Independent Data Monitoring Committee (IDMC) that reviewed findings from the trial, including cardiac safety data and the first interim efficacy analysis based on 322 events. The IDMC has agreed to release the data, as efficacy boundaries have been crossed for the two investigational arms. The relative reduction in the risk of relapse was 51% [95% CI: 35%-63%] and 39% [95% CI: 21%-53%] for the AC-TH and TCH arms, respectively, compared to the AC-T control arm. The IDMC had previously reviewed and released the cardiac safety (cut-off December 31, 2004) that showed the following proportion of protocol-defined cardiac events: 1.2%, 2.3% and 1.2% for the AC-T, AC-TH, and TCH arms respectively. Insufficient information is available at this time to evaluate the secondary endpoint of overall survival.

"In this poor prognosis population of women with HER2-positive breast cancer, the interim efficacy analysis of BCIRG 006 study conducted after 23 months of median follow up, demonstrates that the addition of HERCEPTIN(R) to two TAXOTERE(R)-containing chemotherapy regimens, with or without anthracycline, significantly improved disease-free survival in the adjuvant setting," said Dennis Slamon, PhD, MD, Co-Chair of the BCIRG 006 study and Director of Clinical and Translational Research at UCLA's Jonsson Comprehensive Cancer Center. "In the first interim analysis, this novel regimen of TAXOTERE(R) without anthracyclines appears to avoid the problem of increased cardiotoxicity that has been reported when HERCEPTIN(R) is used together with anthracyclines."

The BCIRG plans to present full interim efficacy and safety results, as well as updated cardiac analyses, during the San Antonio Breast Cancer Symposium in December 2005.

About Breast Cancer

Breast cancer is the most frequently diagnosed cancer in women. It is the second-leading cause of cancer death in women after lung cancer, and since 1990 is increasing predominantly in women 50 and over. It is the first cause of cancer mortality in women of 40 to 59 years old. According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. A woman is diagnosed with breast cancer in the United States every three minutes. The risk of a woman developing breast cancer during her lifetime is approximately 13 percent (about one in seven of all women in the United States). In the European Union, more than 191,000 new cases are diagnosed each year and more than 60,000 women will die. Of women with breast cancer, twenty to 25% of these women will have HER2-positive breast cancers. With earlier screening and diagnosis, early management of patients may offer better chances of survival.

About BCIRG:

BCIRG is the scientific division of a non-for-profit CIRG (Cancer International Research Group), an Academic Research Organization led by internationally recognized cancer researchers. A strong clinical operation division provides a complete range of services to conduct and manage its clinical trials, ranging from small proof of concept studies up to international phase III trials. CIRG is located in Paris (France) and Edmonton AB (Canada).

For information about CIRG/BCIRG, please visit their website: http://www.CIRG.ORG

Contact: Mary-Ann LINDSAY; Director of Scientific Development +1(780) 702 0223, fax: +1(780)702 0190. mary-ann.lindsay@cirg.org Emmanuelle MEKERCKE, Manager of communication +33(1)58 10 08 97, fax: +33(1)58100905. Emmanuelle.mekercke@cirg.org About TAXOTERE(R)

TAXOTERE(R) is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and it is also approved in combination with doxorubicin and cyclophosphamide (TAC regimen) for the adjuvant (post surgery) treatment of patients with operable, node-positive breast cancer.

TAXOTERE(R) is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin, who had not received prior chemotherapy, and it also is approved for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. In addition, the U.S. Food and Drug Administration has approved TAXOTERE(R) for use in combination with prednisone as a treatment for men with androgen-independent (hormone-refractory) metastatic prostate cancer.

Important safety information

WARNING: TAXOTERE(R) treatment can cause serious, physically limiting, and potentially life-threatening side effects, such as infection, low blood-cell counts, allergic reaction, and retention of excess fluid (edema).

TAXOTERE(R) should not be given to patients with low white-blood-cell counts, abnormal liver function, or a history of allergic reactions to TAXOTERE(R) or any of the ingredients in TAXOTERE(R).

Before each TAXOTERE(R) treatment, all patients treated with TAXOTERE(R) must receive another medicine called dexamethasone. This drug can help reduce the risk of fluid retention (edema) and allergic reactions.

TAXOTERE(R) should be administered only under the supervision of a qualified physician experienced in the use of anticancer treatments. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

Treatment-related acute myeloid leukemia (AML) has occurred in patients given anthracyclines and/or cyclophosphamide, including use with TAXOTERE(R) in adjuvant therapy for breast cancer.

The most common severe side effects are low white-blood-cell count, anemia, fatigue, diarrhea, and mouth and throat irritation. Low white-blood-cell count can lead to life-threatening infections. The earliest sign of infection may be fever, so tell your doctor right away if you have a fever.

Other common side effects from TAXOTERE(R) include nausea, vomiting, hair loss, rash, infusion-site reactions, odd sensations (such as numbness, tingling, or burning) or weakness in the hands and feet, nail changes, muscle and/or bone pain, or excessive tearing.

Patients 65 years of age or older may experience some side effects more frequently than younger patients.

Because of the potential risk of fetal harm, pregnant women should not receive TAXOTERE(R). Women of childbearing potential should avoid becoming pregnant during treatment with TAXOTERE(R).

Before receiving TAXOTERE(R), tell your doctor if * You have any allergies * You are taking any other medicines -- including nonprescription (over-the-counter) drugs, vitamins, and dietary or herbal supplements When taking TAXOTERE(R), contact your doctor if * You have symptoms of an allergic reaction (warm sensation, tightness in your chest, itching/hives, or shortness of breath) * You experience any other side effects

Please see adjacent page for patient information leaflet for detailed information about these side effects, and talk to your doctor about any questions you may have.

For more information about TAXOTERE(R), visit http://www.taxotere.com or see accompanying full prescribing information including boxed WARNING. For more information about ongoing clinical trials, please call 1-800-RxTrial or visit http://www.aventisoncology.com.

About sanofi-aventis

The sanofi-aventis Group is the world's third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris and in New York

Forward Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expect," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2004. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

Sanofi-aventis Group subsidiaries in the United States include Sanofi-Synthelabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc.

U.S. Contacts: Susan Brooks, 908-243-7564, susan.brooks@sanofi-aventis.com Lisa Kennedy, 908-243-6361, lisa.a.kennedy@sanofi-aventis.com

sanofi-aventis

CONTACT: Susan Brooks, +1-908-243-7564, susan.brooks@sanofi-aventis.com,or Lisa Kennedy, +1-908-243-6361, lisa.a.kennedy@sanofi-aventis.com, bothof sanofi-aventis

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