We are a biopharmaceutical company whose mission is to advance oncology care by developing and commercializing a portfolio of targeted treatments designed to address the medical needs of patients with cancer. We focus on what we believe are two promising strategies for treating cancer: growth factor blockers and angiogenesis inhibitors.
We were incorporated under the laws of the State of Delaware on April 26, 1984. Our corporate headquarters and research facility are located at 180 Varick Street, New York, New York 10014 and our telephone number is (212) 645-1405.
Our commercially available product, ERBITUX® (cetuximab), is a first-of-its-kind antibody that was first approved by the United States Food and Drug Administration (FDA) on February 12, 2004, for use in combination with irinotecan in the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and for use as a single-agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy. On March 1, 2006, the FDA approved ERBITUX for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN) and as a single-agent in recurrent or metastatic SCCHN where prior platinum-based chemotherapy has failed. On October 2, 2007, the FDA approved an update to the ERBITUX product labeling to include overall survival data as a single-agent in EGFR-expressing metastatic colorectal cancer patients after failure of both inrinotecan-and oxaliplatin-based regimens.
Please see full prescribing information, available at www.ERBITUX.com, for important safety information relating to ERBITUX, including boxed warnings. ERBITUX binds specifically to the EGFR (also referred to as HER1 and c-ErbB-1) on both normal and tumor cells, and competitively inhibits the binding of the epidermal growth factor (EGF) and other growth stimulatory ligands, such as transforming growth factor-alpha. The EGFR is constitutively expressed in many normal epithelial tissues, including the skin and hair follicle. Expression of EGFR is also detected in many human cancers, particularly carcinomas, including those of the head and neck, colon and rectum, pancreas, stomach, lung, and breast. We are conducting, and in some cases have completed, clinical studies evaluating ERBITUX for broader use in colorectal, head and neck, lung, pancreatic, esophageal, stomach, prostate, bladder, and other cancers, as well as other potential indications.
In September 2005, Health Canada approved ERBITUX for use in combination with irinotecan for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory to other irinotecan-based chemotherapy regimens and for use as a single-agent for the treatment of EGFR expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy. However, ERBITUX is not currently being actively promoted in Canada.
On December 1, 2003, Swissmedic, the Swiss agency for therapeutic products, approved ERBITUX in Switzerland for the treatment of patients with colorectal cancer who no longer respond to standard chemotherapy treatment with irinotecan. Merck KGaA licensed the right to market ERBITUX outside the U.S. and Canada from the Company in 1998. In Japan, Merck KGaA has marketing rights to ERBITUX, which are co-exclusive to the co-development rights of the Company and Bristol-Myers Squibb Company (BMS). On June 30, 2004, Merck KGaA received marketing approval by the European Commission to sell ERBITUX for use in combination with irinotecan for the treatment of patients with EGFR-expressing metastatic colorectal cancer after failure of irinotecan including cytotoxic therapy. On December 22, 2005, Swissmedic approved ERBITUX in Switzerland in combination with radiation in the treatment of patients with previously untreated advanced SCCHN.
On January 31, 2007, an application was submitted to the Japanese Pharmaceuticals and Medical Device Agency for the use of ERBITUX in treating patients with advanced colorectal cancer. ERBITUX is the first immunoglobulin G-1 (IgG1) monoclonal antibody that inhibits EGFR to be submitted for marketing authorization in Japan.
We co-promote and otherwise support the sale of ERBITUX in the U.S. and Canada together with our development, promotion and distribution partner BMS through its wholly-owned subsidiary E.R. Squibb & Sons, L.L.C. (E.R. Squibb). We manufacture ERBITUX for clinical studies and for commercial sales. According to our agreements with BMS and Merck KGaA, each is obligated to pay us certain royalties on their sales of ERBITUX.
In addition to achieving approval in the above indications, we also have completed a comprehensive clinical development program to evaluate the broader use of ERBITUX in colorectal cancer, including two Phase III randomized studies known as EMR-013 (also known as CRYSTAL; first-line metastatic setting), and BMS-006 (also known as EPIC; second-line metastatic setting). The first-line metastatic study EMR-013 met its primary endpoint by significantly improving progression-free survival. In the Phase III randomized study BMS-006, the primary endpoint, overall survival, was not met, possibly because a high proportion of patients in the control (irinotecan only) arm received treatment with ERBITUX following development of progressive cancer, potentially confounding the interpretation of this endpoint. However, the secondary endpoints strongly favor the ERBITUX combination arm.
In collaboration with the National Cancer Institute (NCI) Cooperative groups, studies in first-line colorectal cancer (CALGB 80203) and a first-line pancreatic cancer Phase III study (Southwest Oncology Group (SWOG) 0205) began to enroll patients in 2004. In April 2007, SWOG announced that SWOG 0205 did not meet its endpoint of improving overall survival. Subsequently CALGB 80203 was closed to enrollment after accruing 238 patients and a new first-line colorectal cancer protocol that incorporates both ERBITUX and Avastin® (bevacizumab) developed by CALGB (80405) began enrolling patients in late 2005 by all of the NCI Cooperative groups (Intergroup). Furthermore, the NCI Cooperative groups began a Phase III randomized study to evaluate the merits of adding ERBITUX in the adjuvant setting following definitive surgical treatment of Stage C (locoregional) colorectal cancer. A similar adjuvant study (PETACC-8) was also begun in Europe and other regions outside the U.S.. In September 2007, ImClone and its partners Merck KGaA and BMS announced that its pivotal Phase III study evaluating ERBITUX in patients with advanced non-small cell lung cancer (NSCLC) met its primary endpoint of increasing overall survival. In addition, numerous registration-directed studies of ERBITUX are underway in various other locoregional and advanced disease settings (colorectal, non-small cell lung, head and neck, stomach, esophageal, pancreatic, bladder, prostate, and other cancers) and pilot studies are either underway or planned to further evaluate the development of ERBITUX for other indications and tumor types.
In addition to our work developing and commercializing ERBITUX, we have also advanced a number of investigational fully-human IgG1 monoclonal antibodies to various stages of clinical development, including those targeting angiogenesis and growth signaling mechanisms, which can be used to treat various kinds of cancer and nonmalignant diseases. We continue to conduct research, both independently and in collaboration with academic, community and corporate partners, in a number of areas related to our core focus of tumor cell growth factor inhibitors and angiogenesis inhibitors.
CLINICAL DEVELOPMENT PROGRAMS
ERBITUX Cancer Therapeutic
ERBITUX is an IgG1 chimerized (part human, part mouse) monoclonal antibody that selectively binds to the EGFR and thereby inhibits growth of tumors dependent upon activation of the EGFR for cell division and survival. The activation of the EGFR is believed to play a critical role in the growth and survival of certain types of tumor cells and select normal cells and in vitro has been shown to be a mediator of antibody-dependent cellular cytotoxicity (ADCC). Certain cancer types are characterized by the expression of the EGFR. For example, IMCL-9923 and other studies conducted by us have indicated that approximately 75% of advanced stage refractory colorectal cancer cases have been shown by immunohistochemistry (IHC) to have detectable EGFR in tumor cells as assessed by IHC, although it appears that nearly all colorectal cancers have the genetic machinery for EGFR and manufacture EGFR mRNA. Similarly, according to the literature in this area, nearly all patients diagnosed with SCCHN have been shown to express the EGFR on the surface of the tumor cells, as assessed by IHC. Other types of cancer are also characterized, in certain patients, by expression of the EGFR, including non-small cell lung, renal, and pancreatic cancers. By preventing the binding of critical growth factors to the EGFR, we believe it is possible to inhibit the growth and survival of these and other cancers. ERBITUX may increase the anticancer activity of radiotherapy by one of two postulated mechanisms: (1) EGFR inhibition induces arrest in G1, the phase of the cell cycle in which radiosensitivity is highest and (2) irradiation induces upregulation and tryrosine phosphorylation of EGFR; irradiated cells may then become dependent on EGFR signaling for proliferation. EGFR inhibition may then impair these radioprotective responses.
ERBITUX Clinical Studies
The charts presented below reflect potentially pivotal studies in selected tumor types that we and our partners, Merck KGaA and BMS, are developing or collaborating on with the NCI and various European cooperative groups, and are designed both for registration purposes and exploratory development in these indications. It should be noted that a large number of other clinical evaluations of ERBITUX, including investigator-initiated studies and studies sponsored by ImClone, BMS, and Merck KGaA, are progressing in a broad array of tumor types.