Merck KGaA announced today that it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), for its application to broaden the use of the targeted cancer therapy Erbitux&(R) (cetuximab) to an enlarged label, also including 1st-line treatment of metastatic colorectal cancer (mCRC) in patients with KRAS wild-type tumors
Darmstadt, Germany | May 30, 2008 | Merck KGaA announced today that it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), for its application to broaden the use of the targeted cancer therapy Erbitux&(R) (cetuximab) to an enlarged label, also including 1st-line treatment of metastatic colorectal cancer (mCRC) in patients with KRAS wild-type tumors. The CHMP recommends the use of Erbitux in the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type 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.
The submission was supported in part by data analysis from the major randomized, controlled CRYSTAL(a) and OPUS(b) trials that demonstrated the efficacy of Erbitux in combination with standard chemotherapy in the 1st-line treatment of patients with metastatic colorectal cancer.
The initial analyses of CRYSTAL and OPUS trials in the overall population showed that the addition of Erbitux to standard chemotherapy regimens (FOLFIRI and FOLFOX) led to an increase in efficacy compared to chemotherapy alone. (1,2)
The OPUS trial demonstrated that this effect was even more pronounced in patients with KRAS wild-type tumors, which was reflected in increased response rates, increased progression free survival times and in a decreased risk of progression. As a result, the future product labeling for Erbitux is expected to take into consideration the KRAS mutational status of the patient’s tumor. In clinical practice this would enable physicians to select those patients who will benefit most from Erbitux, thus improving treatment outcomes. KRAS data on the CRYSTAL trial will be presented at the 2008 annual meeting of ASCO.
“The positive opinion from the CHMP is an important step forward in the management of colorectal cancer and a step closer to tailored therapy for cancer patients,” said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono.
Up to 65% of mCRC patients have KRAS wild-type tumors.(3) KRAS is a gene that codes for a protein involved in the EGFR pathway. In “normal,” non-mutated or so-called tumors with wild-type KRAS, the KRAS protein is tightly regulated and only activated in response to certain stimuli such as EGFR signaling allowing an effective blockade of the downstream signaling by the EGFR targeted antibody Erbitux. In mutant KRAS tumors the KRAS protein is permanently “turned on” and therefore it has been hypothesized that the drug’s inhibition of the downstream effects is less efficient and the tumor may continue to grow, proliferate and spread.
Erbitux is an epidermal growth factor receptor (EGFR) targeting therapy that has been licensed in Europe for pre-treated mCRC since June 2004 and locally advanced squamous cell carcinoma of the head and neck (SCCHN) since April 2006.
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.(4) Approximately 25% of patients present with metastatic disease.(5) Five-year survival rates for patients with mCRC are as low as 5%.(6)
(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. ACSO 2007, Abstract No: 4000
2. Bokemeyer C, et al. ASCO 2007, Abstract No: 4035
3. Bamford S, et al. Br J Cancer 2004;91:355-358
4. Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108.
5. Cunningham D and Findley M. Eur J Cancer 1993;29A(15);2077–2079
6. 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 72 countries. It has been approved for the treatment of colorectal cancer in 71 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, Kazakhstan, 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, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.
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 65 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, 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 1st-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: 90
Merck KGaA announced today that it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), for its application to broaden the use of the targeted cancer therapy Erbitux&(R) (cetuximab) to an enlarged label, also including 1st-line treatment of metastatic colorectal cancer (mCRC) in patients with KRAS wild-type tumors
Darmstadt, Germany | May 30, 2008 | Merck KGaA announced today that it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), for its application to broaden the use of the targeted cancer therapy Erbitux&(R) (cetuximab) to an enlarged label, also including 1st-line treatment of metastatic colorectal cancer (mCRC) in patients with KRAS wild-type tumors. The CHMP recommends the use of Erbitux in the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type 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.
The submission was supported in part by data analysis from the major randomized, controlled CRYSTAL(a) and OPUS(b) trials that demonstrated the efficacy of Erbitux in combination with standard chemotherapy in the 1st-line treatment of patients with metastatic colorectal cancer.
The initial analyses of CRYSTAL and OPUS trials in the overall population showed that the addition of Erbitux to standard chemotherapy regimens (FOLFIRI and FOLFOX) led to an increase in efficacy compared to chemotherapy alone. (1,2)
The OPUS trial demonstrated that this effect was even more pronounced in patients with KRAS wild-type tumors, which was reflected in increased response rates, increased progression free survival times and in a decreased risk of progression. As a result, the future product labeling for Erbitux is expected to take into consideration the KRAS mutational status of the patient’s tumor. In clinical practice this would enable physicians to select those patients who will benefit most from Erbitux, thus improving treatment outcomes. KRAS data on the CRYSTAL trial will be presented at the 2008 annual meeting of ASCO.
“The positive opinion from the CHMP is an important step forward in the management of colorectal cancer and a step closer to tailored therapy for cancer patients,” said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono.
Up to 65% of mCRC patients have KRAS wild-type tumors.(3) KRAS is a gene that codes for a protein involved in the EGFR pathway. In “normal,” non-mutated or so-called tumors with wild-type KRAS, the KRAS protein is tightly regulated and only activated in response to certain stimuli such as EGFR signaling allowing an effective blockade of the downstream signaling by the EGFR targeted antibody Erbitux. In mutant KRAS tumors the KRAS protein is permanently “turned on” and therefore it has been hypothesized that the drug’s inhibition of the downstream effects is less efficient and the tumor may continue to grow, proliferate and spread.
Erbitux is an epidermal growth factor receptor (EGFR) targeting therapy that has been licensed in Europe for pre-treated mCRC since June 2004 and locally advanced squamous cell carcinoma of the head and neck (SCCHN) since April 2006.
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.(4) Approximately 25% of patients present with metastatic disease.(5) Five-year survival rates for patients with mCRC are as low as 5%.(6)
(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. ACSO 2007, Abstract No: 4000
2. Bokemeyer C, et al. ASCO 2007, Abstract No: 4035
3. Bamford S, et al. Br J Cancer 2004;91:355-358
4. Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108.
5. Cunningham D and Findley M. Eur J Cancer 1993;29A(15);2077–2079
6. 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 72 countries. It has been approved for the treatment of colorectal cancer in 71 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, Kazakhstan, 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, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.
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 65 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, 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 1st-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: 90
