In keeping with its firm commitment to make innovative therapeutic agents available to physicians and patients and to meet currently unmet medical needs, Sanofi has been focusing major efforts on the research and development of more effective and better tolerated treatments for cancer, one of its core group of targeted therapeutic areas along with thrombosis/cardiovascular disease, disorders of the central nervous system and internal medicine. With a view to becoming an increasingly active player in this field, Sanofi has developed an oncology portfolio in the areas of colorectal and lung cancer via two promising therapeutic agents :

OXALIPLATIN : a new cytotoxic agent marketed by Sanofi in France under the name EloxatineÔ since September 1996 for the treatment of metastatic colorectal cancer after initial chemotherapy has failed. Sanofi recently announced approval of oxaliplatin in France for first-line treatment of metastatic colorectal cancer in association with fluoropyrimidines and as monotherapy in patients for whom the administration of fluoropyrimidines is not appropriate.

Results of a 400-patient trial on oxaliplatin in patients with previously untreated colorectal cancer were recently presented at the American Society of Clinical Oncology annual meeting in Los Angeles. In the trial, patients received either a 5FU/LV regimen or the same regimen plus oxaliplatin. Twice as many patients who received oxaliplatin responded to treatment, and progression-free survival was also significantly prolonged for these patients.

In addition to improved response to treatment, oxaliplatin also appears to be better tolerated than most other cancer treatments, potentially providing an improved quality of life for patients both during and after treatment.

Sanofi is currently seeking product licence approval for oxaliplatin in Europe via the mutual recognition procedure with France as rapporteur and will submit a New Drug Application for the compound to the Food and Drug Administration (FDA) before the end of this year.

TIRAPAZAMINE : In collaboration with Dr. Martin Brown (Stanford University, California, US) and Stanford Research Institute, Sanofi has developed tirapazamine, a novel experimental compound for the treatment of Non-Small Cell Lung Cancer (NSCLC).

Tirapazamine has a unique, selective toxicity against hypoxic cells which have low oxygen levels and are associated with resistance to standard chemotherapy.

The results of the CATAPULT-1 (Cisplatin and Tirapazamine against Previously Untreated Lung Tumors) multi-center, multi-national trial presented recently at the American Society of Clinical Oncology annual meeting in Los Angeles, showed that tirapazamine, in combination with cisplatin therapy, significantly increased the median survival time and one-year survival were significantly improved with the combination of tirapazamine plus cisplatin versus cisplatin alone. Moreover, the tumor response rate was doubled in patients receiving the combination as compared with those receiving the standard cisplatin therapy.

Sanofi is encouraged by these results and is continuing to study tirapazamine in combination with cisplatin in the treatment of patients with NSCLC.

In addition to the above two compounds, Sanofi has a promising compound, URATE OXIDASE to treat one of the dangerous and sometimes lethal side effects of cancer therapy : hyperuricemia.

Severe hyperuricemia, or high levels of uric acid in the body, occurs when chemotherapy causes the massive destruction of tumor cells. Excretion of the highly toxic uric acid, which cannot be destroyed naturally by the human body, can cause kidney failure. This is especially the case in cancers of the blood.

Urate Oxidase is an enzyme that changes uric acid into another non-toxic substance which can be safely excreted by the kidney. This enzyme has been available for some time, but it has been very difficult to purify and costly to produce using traditional manufacturing techniques.

Sanofi has used biotechnology to synthesize Urate Oxidase and this new version is currently undergoing phase III trials.

Sanofi’s diversified approach for cancer treatment is continuing with other compounds in earlier stages of investigation.

With the development of this unique portfolio of compounds, Sanofi is determined to meet the huge healthcare challenge posed by several forms of cancer and to become an active partner in the treatment of the disease.