Merck KGaA announced today that it has been granted approval by the European Commission for Erbitux(R) (cetuximab) to update its license for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer (mCRC) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapies and who are intolerant to irinotecan
Darmstadt, Germany |July 23, 2008 | Merck KGaA announced today that it has been granted approval by the European Commission for Erbitux(R) (cetuximab) to update its license for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer (mCRC) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapies and who are intolerant to irinotecan.
“This broad approval of Erbitux in metastatic colorectal cancer is welcomed by the oncology community as it provides us with another treatment option for our patients in the first-line setting,” commented Professor Eric Van Cutsem, Professor of Medicine and Digestive Oncology at the University Hospital Gasthuisberg in Leuven, Belgium. “We are excited by the data supporting this approval as it demonstrates the increased efficacy of Erbitux in patients who have KRAS wild-type tumors. The broadened approval of Erbitux is also a big step towards offering tailored therapies to patients with metastatic colorectal cancer.”
The approval was granted following review of data from randomized, controlled Phase III (CRYSTALa) and Phase II (OPUSb) trials that demonstrated the superior efficacy of Erbitux in combination with standard chemotherapy in the first-line treatment of patients with mCRC compared to chemotherapy alone.1,2 Further analyses of these trials, investigating the efficacy of Erbitux in patients with KRAS wild-type tumors, was also submitted to the authorities and recently presented at major scientific conferences – American Society of Clinical Oncology (ASCO) and World Congress on Gastro-Intestinal Cancers (WCGIC).3,4,5,6 These analyses found that patients with KRAS wild-type tumors experienced substantially increased efficacy with Erbitux and had statistically significant higher response rates (CRYSTAL: 59% vs 43%; OPUS: 61% vs 37%) and decreased risk of progression (CRYSTAL: by 32%; OPUS by 43%) than patients receiving chemotherapy alone.3,4,5,6
“Erbitux is a key new treatment option for two-thirds of all metastatic colorectal cancer patients because the KRAS status of their tumors is predictive for the efficacy of Erbitux,” said Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. “These findings are an important step forward in the development of tailored therapies.”
Up to 65% of patients with mCRC have normal or non-mutated KRAS tumors, also scientifically known as wild-type.3 KRAS is a gene that codes for a protein involved in the EGFR pathway. In KRAS wild-type tumors, the KRAS protein is tightly regulated and only activated in response to certain stimuli such as EGFR signaling. In patients with normal KRAS status, Erbitux blocks a signaling pathway, preventing growth of a tumor. The KRAS mutation overrules this effect of Erbitux, thus allowing the tumor to continue to grow, proliferate and spread.
Erbitux has been licensed for the treatment of mCRC since June 2004 and locally advanced squamous cell carcinoma of the head and neck (SCCHN) since April 2006. So far, more than 120,000 patients have been treated with commercially available Erbitux worldwide. A submission to the European authorities to broaden the use of Erbitux in SCCHN to include first-line treatment of patients with recurrent and/or metastatic SCCHN was made in June 2008 by Merck.
More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths annually.7 Approximately 25% of patients present with metastatic disease.8 Five-year survival rates for patients with mCRC are as low as 5%.9
a CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer
b OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC
References:
1. Van Cutsem E, et al. ASCO 2007; Abstract No: 4000
2. Bokemeyer C, et al. ASCO 2007; Abstract No: 4035
3. Van Cutsem E, et al. ASCO 2008; Abstract No: 2
4. Bokemeyer C, et al. ASCO 2008; Abstract No: 4000
5. Van Cutsem E, et al. WCGIC 2008; Abstract No: 471
6. Schuch G, et al. WCGIC 2008; Abstract No: 385
7. Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108.
8. Cunningham D and Findley M. Eur J Cancer 1993;29A(15);2077–2079
9. Macdonald JS. CA Cancer J Clin 1999;49(4),202-219.
About Erbitux
Erbitux(R) is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in 74 countries. It has been approved for the treatment of colorectal cancer in 73 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Thailand, Ukraine, Uruguay, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Japan, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela. In the European Union, the license was updated in July 2008 for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type mCRC (metastatic colorectal cancer) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 67 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico,New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Nicaragua, Peru, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.
Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, ImClone Systems Incorporated, Bristol-Myers Squibb Company and Merck jointly develop and, upon approval, commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT(R) (tegafur-uracil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.
Merck is also investigating among other cancer treatments the use of Stimuvax(R) (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Bellevue, Washington, USA.
SOURCE: Merck KGaA
Post Views: 67
Merck KGaA announced today that it has been granted approval by the European Commission for Erbitux(R) (cetuximab) to update its license for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer (mCRC) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapies and who are intolerant to irinotecan
Darmstadt, Germany |July 23, 2008 | Merck KGaA announced today that it has been granted approval by the European Commission for Erbitux(R) (cetuximab) to update its license for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer (mCRC) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapies and who are intolerant to irinotecan.
“This broad approval of Erbitux in metastatic colorectal cancer is welcomed by the oncology community as it provides us with another treatment option for our patients in the first-line setting,” commented Professor Eric Van Cutsem, Professor of Medicine and Digestive Oncology at the University Hospital Gasthuisberg in Leuven, Belgium. “We are excited by the data supporting this approval as it demonstrates the increased efficacy of Erbitux in patients who have KRAS wild-type tumors. The broadened approval of Erbitux is also a big step towards offering tailored therapies to patients with metastatic colorectal cancer.”
The approval was granted following review of data from randomized, controlled Phase III (CRYSTALa) and Phase II (OPUSb) trials that demonstrated the superior efficacy of Erbitux in combination with standard chemotherapy in the first-line treatment of patients with mCRC compared to chemotherapy alone.1,2 Further analyses of these trials, investigating the efficacy of Erbitux in patients with KRAS wild-type tumors, was also submitted to the authorities and recently presented at major scientific conferences – American Society of Clinical Oncology (ASCO) and World Congress on Gastro-Intestinal Cancers (WCGIC).3,4,5,6 These analyses found that patients with KRAS wild-type tumors experienced substantially increased efficacy with Erbitux and had statistically significant higher response rates (CRYSTAL: 59% vs 43%; OPUS: 61% vs 37%) and decreased risk of progression (CRYSTAL: by 32%; OPUS by 43%) than patients receiving chemotherapy alone.3,4,5,6
“Erbitux is a key new treatment option for two-thirds of all metastatic colorectal cancer patients because the KRAS status of their tumors is predictive for the efficacy of Erbitux,” said Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. “These findings are an important step forward in the development of tailored therapies.”
Up to 65% of patients with mCRC have normal or non-mutated KRAS tumors, also scientifically known as wild-type.3 KRAS is a gene that codes for a protein involved in the EGFR pathway. In KRAS wild-type tumors, the KRAS protein is tightly regulated and only activated in response to certain stimuli such as EGFR signaling. In patients with normal KRAS status, Erbitux blocks a signaling pathway, preventing growth of a tumor. The KRAS mutation overrules this effect of Erbitux, thus allowing the tumor to continue to grow, proliferate and spread.
Erbitux has been licensed for the treatment of mCRC since June 2004 and locally advanced squamous cell carcinoma of the head and neck (SCCHN) since April 2006. So far, more than 120,000 patients have been treated with commercially available Erbitux worldwide. A submission to the European authorities to broaden the use of Erbitux in SCCHN to include first-line treatment of patients with recurrent and/or metastatic SCCHN was made in June 2008 by Merck.
More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths annually.7 Approximately 25% of patients present with metastatic disease.8 Five-year survival rates for patients with mCRC are as low as 5%.9
a CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer
b OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC
References:
1. Van Cutsem E, et al. ASCO 2007; Abstract No: 4000
2. Bokemeyer C, et al. ASCO 2007; Abstract No: 4035
3. Van Cutsem E, et al. ASCO 2008; Abstract No: 2
4. Bokemeyer C, et al. ASCO 2008; Abstract No: 4000
5. Van Cutsem E, et al. WCGIC 2008; Abstract No: 471
6. Schuch G, et al. WCGIC 2008; Abstract No: 385
7. Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108.
8. Cunningham D and Findley M. Eur J Cancer 1993;29A(15);2077–2079
9. Macdonald JS. CA Cancer J Clin 1999;49(4),202-219.
About Erbitux
Erbitux(R) is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in 74 countries. It has been approved for the treatment of colorectal cancer in 73 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Thailand, Ukraine, Uruguay, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Japan, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela. In the European Union, the license was updated in July 2008 for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type mCRC (metastatic colorectal cancer) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 67 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico,New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Nicaragua, Peru, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.
Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, ImClone Systems Incorporated, Bristol-Myers Squibb Company and Merck jointly develop and, upon approval, commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT(R) (tegafur-uracil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.
Merck is also investigating among other cancer treatments the use of Stimuvax(R) (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Bellevue, Washington, USA.
SOURCE: Merck KGaA
Post Views: 67
