CMC Comparability Issues Lead to Discontinuation of Erbitux Submission

February 11, 2009

Following a discussion with the US Food and Drug Administration, ImClone Systems, acquired last fall by Eli Lilly and Company (New York, NY), and Bristol-Myers Squibb (New York, NY) have withdrawn the supplemental Biologics License Application for the use of Erubitux (cetuximab) in advanced non-small cell lung cancer.

Following a discussion with the US Food and Drug Administration, ImClone Systems, acquired last fall by Eli Lilly and Company (New York, NY), and Bristol-Myers Squibb (New York, NY) have withdrawn the supplemental Biologics License Application for the use of Erubitux (cetuximab) in advanced non-small cell lung cancer. This decision was based upon a chemistry manufacturing and controls (CMC) matter with regard to the preclinical pharmacokinetic comparability of the US marketed version of Erubitux with the clinical supplies used by Merck KGaA (ImClone’s partner for Erubitux outside of North America). The sBLA may be resubmitted in the future.

The discussions with FDA do not have any impact on currently-marketed Erubitux, including the safety and efficacy of the product for approved indications.

Erubitux (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1), expressed on the surface of normal and tumor cells called. In vitro assays and in vivo animal studies have shown that binding of Erubitux 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, Erubitux can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that Erubitux inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of Erubitux were observed in human tumor xenografts lacking EGFR expression.