ImClone Systems (NASDAQ: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY) announced today that an application has been submitted with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the use of ERBITUX® (Cetuximab) in treating patients with advanced colorectal cancer. ERBITUX is the first IgG1 monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR) to be submitted for marketing authorization in Japan.

The Japanese submission was based on results from studies conducted in Europe and Japan which confirm the activity of ERBITUX in patients with metastatic colorectal cancer.

In Japan, the incidence of colorectal cancer has increased markedly during the last 50 years(1). Among men and women in Japan, the incidence is higher than for lung cancer (95,651 per year vs 66,453) and second to stomach cancer (95,651 per year vs 109,779). In terms of mortality, the ranking is slightly different: Colorectal cancer is now the third biggest cancer threat in Japan after lung and stomach cancer (38,206, 56,367 and 54,423 people per year, respectively)(2). Approximately 25 percent of colorectal cancer patients present with metastatic disease(3).

The filing in Japan is a result of a development collaboration between ImClone Systems, Bristol-Myers Squibb, and Merck KGaA of Darmstadt, Germany.

About ERBITUX (Cetuximab)

ERBITUX is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumor cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of ERBITUX to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, ERBITUX can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. While the mechanism of ERBITUX' anti-tumor effect(s) in vivo is unknown, all of these processes may contribute to the overall therapeutic effect of ERBITUX. EGFR is part of a signaling pathway that is linked to the growth and development of many human cancers, including those of the head and neck, colon and rectum.

In the U.S., ERBITUX, in combination with radiation therapy, is indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. ERBITUX as a single agent is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed.

ERBITUX is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma (mCRC) in combination with irinotecan for patients who are refractory to irinotecan-based chemotherapy, and as a single agent for patients who are intolerant to irinotecan-based therapy. The effectiveness of ERBITUX for the treatment of EGFR-expressing mCRC cancer is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX for the treatment of EGFR-expressing mCRC.

For full prescribing information, including boxed WARNINGS regarding infusion reactions and cardiopulmonary arrest, visit erbitux/.

Important Safety Information

Grade 3/4 infusion reactions, rarely with fatal outcome (