ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, announced that ERBITUX® (cetuximab) has been commercially launched in Japan for use in treating patients with advanced or metastatic colorectal cancer (mCRC). The launch of ERBITUX in Japan is the result of a co-development and co-commercialization agreement between ImClone, Bristol-Myers Squibb Company and Merck KGaA, Darmstadt, Germany.
ERBITUX is the first ever epidermal growth factor receptor, or EGFR, targeted monoclonal antibody to receive marketing authorization in Japan. In July 2008, ERBITUX received marketing authorization in Japan to treat patients with EGFR-positive, curatively unresectable (inoperable), advanced or recurrent CRC, and to use in combination with irinotecan in second and further lines of mCRC. Bristol-Myers Squibb and Merck KGaA have now fully launched their respective sales force detailing activities for medical institutions in Japan to make ERBITUX available to patients with mCRC.
“We are pleased that ERBITUX is now commercially available as a treatment option for colorectal cancer patients in Japan, where this type of cancer is the second most prevalent and afflicts nearly 100,000 individuals each year,” said Joseph I. DePinto, Vice President, Commercial Operations of ImClone. “ImClone remains committed to maximizing the potential of ERBITUX as an effective therapy for cancer patients around the world.”
Under the terms of the co-development and co-commercialization agreement of ERBITUX in Japan, Merck Serono Co., Ltd. will distribute the product and record the sales for the collaboration. The terms of this agreement provide that Merck KGaA will receive 50 percent of the profit/loss from sales in Japan, and ImClone and Bristol-Myers Squibb will each receive 25 percent. The sharing of profit/loss reflects the co-exclusive rights to ERBITUX in Japan previously granted by ImClone to Merck KGaA and Bristol-Myers Squibb. In addition to its percentage of profits, ImClone will receive from Merck KGaA a 4.75 percent royalty of total net sales in Japan.
The co-development and co-commercialization agreement between ImClone, Bristol-Myers Squibb and Merck KGaA (along with the Japanese subsidiaries of Bristol-Myers Squibb and Merck LTD) is for the joint development and marketing of ERBITUX in Japan for the treatment of EGFR-expressing mCRC, as well as for the treatment of any other cancers the three companies agree to pursue.
About Colorectal Cancer
In Japan, the incidence of colorectal cancer has increased markedly during the last 50 years. Among men and women in Japan, the incidence is higher than for lung cancer (95,651 per year versus 66,453) and second to stomach cancer (95,651 per year versus 109,779). In terms of mortality, the ranking is slightly different; colorectal cancer is now the third largest cancer threat in Japan after lung and stomach cancer (38,206, 56,367 and 54,423 people per year, respectively). Approximately 25 percent of colorectal cancer patients present with metastatic disease or cancer that has spread to other organs. EGFR is expressed in 60-80 percent of colorectal cancer tumors.
About ERBITUX® (Cetuximab)
ERBITUX (cetuximab) 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. In vitro assays and in vivo animal studies have shown that ERBITUX inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of ERBITUX were observed in human tumor xenografts lacking EGFR expression.
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
ERBITUX, in combination with radiation therapy, is indicated for the initial 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, as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single agent, is also indicated for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant to irinotecan-based regimens.
ERBITUX, in combination with irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. The effectiveness of ERBITUX in combination with irinotecan is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX in combination with irinotecan for the treatment of EGFR-expressing metastatic colorectal carcinoma.
For full prescribing information, including boxed WARNINGS regarding infusion reactions and cardiopulmonary arrest, visit ERBITUX.
Important Safety Information
Grade 3/4 infusion reactions occurred in approximately 3% of patients receiving ERBITUX (Cetuximab) in clinical trials, with fatal outcome reported in less than 1 in 1000. Serious infusion reactions, requiring medical intervention and immediate, permanent discontinuation of ERBITUX, included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, loss of consciousness, and/or cardiac arrest. Most reactions (90%) were associated with the first infusion of ERBITUX despite premedication with antihistamines. Caution must be exercised with every ERBITUX infusion, as there were patients who experienced their first severe infusion reaction during later infusions. Monitor patients for 1 hour following ERBITUX infusions in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen). Longer observation periods may be required in patients who require treatment for infusion reactions.
Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of 208 patients with squamous cell carcinoma of the head and neck treated with radiation therapy and ERBITUX, as compared to none of 212 patients treated with radiation therapy alone. Fatal events occurred within 1 to 43 days after the last ERBITUX treatment. Carefully consider the use of ERBITUX in combination with radiation therapy in head and neck cancer patients with a history of coronary artery disease, congestive heart failure or arrhythmias in light of these risks. Closely monitor serum electrolytes including serum magnesium, potassium, and calcium during and after ERBITUX therapy.
Interstitial lung disease (ILD), which was fatal in one case, occurred in 4 of 1570 (