Clinical trials expanded with novel vaccine for advanced colorectal cancer

New sites enrolling for advanced disease; second study to evaluate in earlier-stage disease

Toronto, Canada (January 30, 2003) ? Several additional cancer centers in the United States and Canada are enrolling patients in an innovative clinical trial evaluating the use of a therapeutic cancer vaccine in patients with first-line metastatic colorectal cancer. In addition, a second trial using the vaccine earlier in the course of disease is now under way in centers across Canada, according to Aventis Pasteur Limited of Toronto, Canada, the study sponsor.

Both studies are designed to determine how the investigational vaccine, ALVAC-CEA/B7.1, can be most effective when integrated with standard chemotherapy regimens to treat colon cancer. ALVAC-CEA/B7.1 is a unique cancer vaccine under development that uses a viral vector system derived from the canarypox virus. It is engineered to target the carcinoembryonic antigen (CEA), which is a protein that is overexpressed on the surface of the majority of colorectal cancer cells.

“We are committed to pursuing multiple routes to determine whether ALVAC-CEA/B7.1 has a role in improving overall outcomes when used with chemotherapy to treat colon cancer,” said Neil Berinstein, M.D., Assistant Vice President Clinical Oncology, Program Director, Cancer, Aventis Pasteur. “By adding more trial locations for our first study, and initiating the second study, we are demonstrating our confidence in moving the ALVAC vaccine forward.”

Clinical Trial Sites Enrolling Across U.S. and Canada

New clinical trial sites for patients with metastatic colon cancer have been established in the following cities: Chicago (two sites); Tampa, FL; Portland, OR; and Dunmore, PA; Toronto, Ottawa, and Montreal. Other sites have been enrolling patients in New York City; Washington, DC; Philadelphia; Los Angeles; and Birmingham, AL.

Trial sites enrolling patients with earlier-stage colorectal cancer are in Toronto (two sites); Ottawa; Vancouver; Edmonton; Calgary; and Montreal. For more information about study locations and patient eligibility, individuals should contact Aventis Pasteur Limited, in Toronto, Canada, the sponsor of both studies, at 1-866-455-0349 (toll-free), or visit www.cancervaccines.com.

Cancer Vaccine Strategy: Target Unique Marker on Cancer Cell, Trigger Immune Response

Unfortunately, cancer cells are largely tolerated rather than destroyed by the body’s immune system. But special proteins or antigens, found predominantly in cancer cells, can serve as potential targets for the immune system to attack. In developing vaccines for cancer, the challenge is to find targets that are only found on the cancer cell and to use these targets to effectively reawaken the immune system to overcome its so-called tolerance to cancer, and to launch an attack on the targeted cancer cells. Researchers engineered the ALVAC-CEA/B7.1 vaccine so that for a short period of time, it produces a self-limiting, harmless infection, which causes infected cells to temporarily display the antigen CEA. CEA is found on the surface of about 95% of colorectal cancer cells. In response, the immune system becomes activated and attacks the tumor cells.

“While the ALVAC-CEA/B7.1 vaccine is designed to target one antigen involved in colorectal cancer, we also are studying the feasibility of a multi-antigen approach in future vaccine development,” noted Dr. Berinstein. “We also plan to explore whether vaccines should be used in combination with other anticancer agents like biologics or immunotherapy.”

Current ALVAC-CEA/B7.1 Vaccine Study Designs

The metastatic trial is a pilot phase II study, designed to assess the safety and immunologic activity of ALVAC-CEA/B7.1 when administered at the same time as chemotherapy. Up to 90 patients not yet treated for metastatic colorectal cancer (cancer that has spread to other body parts) will be randomly assigned to one of three treatment arms.

The first group will be vaccinated with ALVAC-CEA/B7.1 before starting chemotherapy and will receive additional doses of the vaccine with each cycle of chemotherapy. The second group will receive doses of tetanus toxoid in addition to the ALVAC-CEA/B7.1 and chemotherapy regimen (to determine whether tetanus toxoid helps to further enhance the immune response). The third group will receive chemotherapy alone. Patients in this group who achieve a partial or complete response after completing chemotherapy will have the option to receive ALVAC-CEA/B.71. The chemotherapy regimen used in this trial is Camptosar (irinotecan or CPT-11), 5-fluorouracil and leucovorin, which is the standard, first-line therapy for metastatic colorectal cancer.

The second trial is designed to evaluate the safety and immunologic activity of ALVAC-CEA/B7.1 when administered at the same time as chemotherapy or following chemotherapy in patients with Stage III colorectal cancer (tumors that invaded through several layers of the colon or rectum, or that have spread to lymph nodes). In this Phase I trial, a total of 60 patients will be randomized into two groups. The first group will receive one ALVAC-CEA/B7.1 vaccine before starting chemotherapy, followed by three weekly doses during the first cycle of chemotherapy, then one vaccination with each chemotherapy cycle (up to six cycles), and vaccinations every two months for up to one year. The second group will receive four ALVAC-CEA/B7.1 vaccinations during the first month following completion of chemotherapy, and one dose a month for another five months. The chemotherapy used in this trial is 5-fluorouracil and leucovorin, which is currently the standard therapy for patients with this stage of the disease.

The investigational vaccine and other ALVAC-based formulations have shown promise in early clinical studies of the vaccine as a single agent conducted by the U.S. National Cancer Institute, in collaboration with Therion Biologics of Cambridge, MA, which demonstrated that ALVAC-based recombinants are safe, with a non-overlapping toxicity profile to chemotherapy. In general, treatments were well tolerated, with no significant product-related toxicities. Side effects associated with the vaccine included mild, local reactions.

Colorectal cancer is the most common cancer of the gastrointestinal tract and the second leading cause of cancer-related morbidity and mortality. There are approximately 300,000 new cases and 200,000 deaths in North America and Europe each year. An estimated 70% of patients are initially diagnosed with treatable forms of the disease, but 25% of these patients will still experience recurrence, which frequently leads to death due to metastatic disease.

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Aventis Pasteur SA is the largest company in the world devoted entirely to vaccines. In 2001, Aventis Pasteur produced 1.3 billion doses of vaccine, making it possible to protect 500 million people across the globe, which is over one million per day. The company offers the broadest range of vaccines, providing protection against 19 bacterial and viral diseases. Based in Lyon, France, Aventis Pasteur is owned by Aventis SA.

The company is a leader in the research and development of therapeutic vaccines for cancer. The two leading cancer vaccines currently in clinical development are for colorectal cancer and melanoma, and the company is actively pursuing additional cancer targets. The corporation’s global cancer vaccine program is anchored in Canada.

Aventis is dedicated to improving life by treating and preventing human disease through the discovery and development of innovative prescription drugs for important therapeutic areas as well as human vaccines. In 2001, Aventis generated sales of ? 17.7 billion, invested ? 3 billion in research and development and employed approximately 75,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. For more information, please visit: www.aventis.com and www.aventispasteur.com.

This release contains information about investigational products not approved for use. Statements in this news release other than historical information are forward-looking statements subject to risks and uncertainties. Actual results could differ materially depending on factors such as the availability of resources, the timing and effects of regulatory actions, the strength of competition, the outcome of litigation and the effectiveness of patent protection. Additional information regarding risks and uncertainties is set forth in the current Annual Report on Form 20-F of Aventis on file with the Securities and Exchange Commission.

Canadian Press Contact:
Nancy Simpson
Aventis Pasteur Limited, Toronto
Tel: 416-667-2955