Inclusion Of Six-Year Overall Survival Data In The Eloxatin(R) (oxaliplatin Injection) Prescribing Information Granted FDA Priority Review

Main Category: Colorectal Cancer
Also Included In: Regulatory Affairs / Drug Approvals;  Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 21 Feb 2008 - 0:00 PDT

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Sanofi-aventis announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and assigned priority review status to a supplemental new drug application (sNDA) that proposes changes to the Eloxatin(R) (oxaliplatin injection) prescribing information (PI) to include a six-year analysis from the MOSAIC trial. In the proposed PI changes, sanofi-aventis is seeking the inclusion of six-year overall survival and five-year disease free survival data in Stage III colon cancer patients treated with either FOLFOX4 (Eloxatin- based chemotherapy regimen) or standard infusional 5-FU/LV-based chemotherapy alone, following surgery to remove the primary tumor.

A priority review designation sets the target date for the completion of the FDA's review of the proposed changes at or before six months from the date of filing.

"We are pleased that FDA is giving priority review to our application for a label change to include updated six-year overall survival data," said Dr. Nassir Habboubi, Vice President of U.S. Medical Affairs, Oncology, for sanofi- aventis. "Inclusion of these data in the prescribing information would provide physicians with a more updated analysis than the existing PI and will help them better evaluate the use of prescribing an Eloxatin(R)-based chemotherapy regimen for their Stage III colon cancer patients."

In the MOSAIC trial, Stage III colon cancer patients treated after complete surgical resection of the tumor with Eloxatin in combination with infusional 5-FU/LV had a significant reduction (20%) in the risk of dying after a median of six years compared to standard 5FU/LV-based chemotherapy alone (hazard ratio of 0.80, confidence interval [0.65, 0.97], p=0.023). Also, disease-free survival (risk of disease recurrence) was improved by 22% in Stage III patients (HR=0.78 [CI: 0.65, 0.93], p=0.005).

In the MOSAIC trial, the most frequently reported side effect was neutropenia (decrease in the number of white blood cells), with 78.9% of patients affected. Neutropenia was complicated by fever or infection in only 1.8% of cases. 92.1% of patients treated with FOLFOX4 had peripheral sensory neuropathy ("tingling or numbness" in the fingers or toes). Of these events, 12% were severe (grades 3 and 4), and half (48.2%) of the episodes were grade 1. Among patients experiencing grade 3 peripheral sensory neuropathy, partial or total recovery was observed in most cases within 18 months following treatment. Patients receiving FOLFOX4 also reported nausea (73.7%), diarrhea (56.3%) and vomiting (47.2%).

Background on MOSAIC

The MOSAIC Study was conducted in 148 centers in 20 countries and supported by sanofi-aventis. In this phase III randomized-controlled trial, 2,246 patients with Stage II or Stage III colon cancer whose tumor had been completely surgically removed randomly received 5-FU/LV (n=1,123) or FOLFOX4 (n=1,123) every two weeks for 12 cycles. The primary endpoint evaluated how the addition of Eloxatin(R) affected disease-free survival at three years. Secondary endpoints included overall survival and safety, including long-term adverse effects. Based on the data from MOSAIC, Eloxatin(R) in combination with infusional 5-FU/LV was granted U.S. approval in 2004 for the treatment of Stage III colon cancer patients who have their primary tumors surgically removed. At the time of the original analysis, there was no demonstrated benefit in overall survival after a median follow-up of four years.

About Colorectal Cancer

At Stage II, the cancer has grown through the wall of the colon or rectum but has not yet spread to nearby lymph nodes. In Stage III, the cancer has invaded one or more of the local lymph nodes but has not spread to distant sites. Metastatic colorectal cancer means that the cancer has spread to other nodes and/or organs in the body.

Colorectal cancer is a leading cause of death. Every year, about one million new cases of colorectal cancer are diagnosed worldwide. About 150,000 new cases are detected each year in the United States. According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related death in the U.S., accounting for about 10% of all cancer deaths. Over a lifetime, about 1 in 18 people develop colorectal cancer, and more than 52,000 people are expected to die from it in the U.S. this year.

Please see accompanying full prescribing information, including BOXED WARNING, and visit http://www.eloxatin.com for more information about Eloxatin(R).

About Sanofi Aventis

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT PARIS: SAN) and in New York (NYSE: SNY).

Sanofi Aventis
http://www.sanofi-aventis.com

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