First approval in Japan of a monoclonal antibody cancer therapy targeting the epidermal growth factor receptor
Darmstadt,Germany | July 16, 2008 | Merck KGaA announced today that marketing authorization has been granted in Japan for the use of Erbitux(R) (cetuximab) in treating patients with epidermal growth factor receptor (EGFR)-positive, curatively unresectable (inoperable), advanced or recurrent colorectal cancer (CRC). On the basis of the submitted data, the label allows the use of Erbitux plus irinotecan in second- and further lines of metastatic colorectal cancer (mCRC).*
Erbitux was approved following the submission by Merck Ltd. Japan to the Ministry of Health, Labor and Welfare (MHLW) on January 31, 2007.
“With the increasing incidence of colorectal cancer in the Japanese population, this approval will bring a much needed new treatment option for these cancer patients,” said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono.
The Japanese submission was mainly based on data from six different studies: two international Phase III studies – the NCIC CTG (National Cancer Institute of Canada Clinical Trial Group) CO.17 study1 and EPIC (European Prospective Investigation of Cancer),2 two European studies – BOND (Bowel Oncology with Cetuximab Antibody)3 and MABEL (Monoclonal Antibody Erbitux in a European Pre-License),4 and two studies conducted in Japanese patients.5,6
Phase III international studies
The NCIC CTG CO.17 Phase III trial was conducted by the NCIC CTG in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), involved 572 patients whose mCRC had progressed with all available standard chemotherapies – irinotecan, oxaliplatin, and fluoropyrimidines. The study demonstrated that treating patients with Erbitux as a monotherapy improved overall median survival time by 32% – 6.1 months with Erbitux compared with 4.6 months with best supportive care alone.1
The other Phase III trial was the multinational EPIC study, which involved 1,298 patients with mCRC whose cancer had progressed on first-line treatment with oxaliplatin-based chemotherapy. Patients were treated with either Erbitux plus irinotecan-based chemotherapy or irinotecan-based chemotherapy alone.
Overall survival did not differ significantly between the two trial arms. However, this may have been because almost half of the patients in the control arm received Erbitux plus irinotecan as post study treatment after failing irinotecan therapy. With patients in both arms of the trial receiving Erbitux, the ultimate survival difference between the two study groups could have been minimized. Notably, patients in the Erbitux-plus-irinotecan-based chemotherapy arm had significantly longer progression-free survival (4.0 months vs 2.6 months; p<0.0001) compared with patients in the irinotecan-based chemotherapy alone arm.2 Response rates were also higher for patients treated with Erbitux (16.4% vs 4.2%; p<0.0001).2
European studies
The BOND study, which included 218 patients, demonstrated that the combination of Erbitux and irinotecan-based chemotherapy in the treatment of patients with mCRC whose cancer had progressed on irinotecan-based chemotherapy, slowed progression of the disease to more than four months in comparison to Erbitux alone.3 In addition, a remarkably high response rate of 23% was also observed in the combination arm.3
The MABEL study was conducted in 1,147 patients whose mCRC had progressed on irinotecan-based chemotherapy. A response rate of 20% and a median overall survival time of 9.2 months was demonstrated when patients were administered Erbitux in combination with irinotecan-based chemotherapy – findings consistent with the BOND study.4
Japanese studies
A Phase II study in Japanese patients with CRC whose cancer had progressed on irinotecan-based chemotherapy demonstrated comparable efficacy and safety results for Erbitux in combination with irinotecan in Japanese patients as were seen in the BOND and MABEL studies in non Japanese patients.5
In addition a Phase I study in Japanese patients with solid tumors assessed the safety and pharmacokinetic profile of Erbitux as a single agent.6 Results showed that Erbitux is well tolerated as a single agent in Japanese patients.6
“Merck Serono is very pleased to be able to bring this valuable treatment option to patients and physicians in Japan, and to help to improve outcomes for cancer sufferers," said Wayne Paterson, President of Merck Serono Japan.
In Japan, the incidence of CRC has increased markedly during the last 50 years7 with currently around 95,651 cases every year.8 It has become the most common cancer among women and the second most common among men, after stomach cancer.8 Colorectal cancer is the third-leading cause of cancer mortality in Japan, accounting for around one in seven cancer deaths8 – a figure which is in part related to the number of people who first present with metastatic CRC (approximately 25% of patients).9
Erbitux was first approved for the treatment of mCRC in Switzerland in December 2003. It was approved for use in the United States by the FDA in February 2004, followed by EMEA approval for Europe in June 2004. The development of Erbitux in Japan was based on a collaborative effort between Merck KGaA, ImClone Systems Inc., Bristol-Myers Squibb Company, Merck Ltd. Japan and Bristol-Myers K.K.
*Original Label Text:
Erbitux is approved for EGFR-positive curatively unresectable advanced or recurrent colorectal cancer
*Precautions in use on indication:
(1) The efficacy and safety of adjuvant setting of Erbitux has not been established.
(2) The efficacy and safety of first-line setting of Erbitux have not been established.
(3) In order to determine the target population, it is advisable to become acquainted with CLINICAL STUDY RESULTS, as well as the efficacy and safety of Erbitux.
References:
1. Jonker DJ, O’Callaghan CJ, Karapetis CS et al. NEJM 2007; 357: 2040-2048.
2. Scheithauer W, Sobrero A, Lenz HJ et al. ECCO 2007.
3. Cunningham D, Humblet Y, Siena S, et al. N Engl J Med 2004;22;351(4):337-45.
4. Wilke H, Glynne-Jones R, Thaler J, et al. J Clin Oncol 2006; 24(18S):Abstract 3549.
5. Data on File.
6. Yasui H, Shirao K, Yamamoto N, et al. ASCO 2005, abstract # 3209.
7. Koyama Y and Kotake K. Dis Colon Rectum. 1997; 40: S2-9.
8. http://www-dep.iarc.fr/ (Globocan 2002).
9. Cunningham D and Findlay M. Eur J Cancer 1993; 29A: 2007–79.
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 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: 61
First approval in Japan of a monoclonal antibody cancer therapy targeting the epidermal growth factor receptor
Darmstadt,Germany | July 16, 2008 | Merck KGaA announced today that marketing authorization has been granted in Japan for the use of Erbitux(R) (cetuximab) in treating patients with epidermal growth factor receptor (EGFR)-positive, curatively unresectable (inoperable), advanced or recurrent colorectal cancer (CRC). On the basis of the submitted data, the label allows the use of Erbitux plus irinotecan in second- and further lines of metastatic colorectal cancer (mCRC).*
Erbitux was approved following the submission by Merck Ltd. Japan to the Ministry of Health, Labor and Welfare (MHLW) on January 31, 2007.
“With the increasing incidence of colorectal cancer in the Japanese population, this approval will bring a much needed new treatment option for these cancer patients,” said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono.
The Japanese submission was mainly based on data from six different studies: two international Phase III studies – the NCIC CTG (National Cancer Institute of Canada Clinical Trial Group) CO.17 study1 and EPIC (European Prospective Investigation of Cancer),2 two European studies – BOND (Bowel Oncology with Cetuximab Antibody)3 and MABEL (Monoclonal Antibody Erbitux in a European Pre-License),4 and two studies conducted in Japanese patients.5,6
Phase III international studies
The NCIC CTG CO.17 Phase III trial was conducted by the NCIC CTG in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), involved 572 patients whose mCRC had progressed with all available standard chemotherapies – irinotecan, oxaliplatin, and fluoropyrimidines. The study demonstrated that treating patients with Erbitux as a monotherapy improved overall median survival time by 32% – 6.1 months with Erbitux compared with 4.6 months with best supportive care alone.1
The other Phase III trial was the multinational EPIC study, which involved 1,298 patients with mCRC whose cancer had progressed on first-line treatment with oxaliplatin-based chemotherapy. Patients were treated with either Erbitux plus irinotecan-based chemotherapy or irinotecan-based chemotherapy alone.
Overall survival did not differ significantly between the two trial arms. However, this may have been because almost half of the patients in the control arm received Erbitux plus irinotecan as post study treatment after failing irinotecan therapy. With patients in both arms of the trial receiving Erbitux, the ultimate survival difference between the two study groups could have been minimized. Notably, patients in the Erbitux-plus-irinotecan-based chemotherapy arm had significantly longer progression-free survival (4.0 months vs 2.6 months; p<0.0001) compared with patients in the irinotecan-based chemotherapy alone arm.2 Response rates were also higher for patients treated with Erbitux (16.4% vs 4.2%; p<0.0001).2
European studies
The BOND study, which included 218 patients, demonstrated that the combination of Erbitux and irinotecan-based chemotherapy in the treatment of patients with mCRC whose cancer had progressed on irinotecan-based chemotherapy, slowed progression of the disease to more than four months in comparison to Erbitux alone.3 In addition, a remarkably high response rate of 23% was also observed in the combination arm.3
The MABEL study was conducted in 1,147 patients whose mCRC had progressed on irinotecan-based chemotherapy. A response rate of 20% and a median overall survival time of 9.2 months was demonstrated when patients were administered Erbitux in combination with irinotecan-based chemotherapy – findings consistent with the BOND study.4
Japanese studies
A Phase II study in Japanese patients with CRC whose cancer had progressed on irinotecan-based chemotherapy demonstrated comparable efficacy and safety results for Erbitux in combination with irinotecan in Japanese patients as were seen in the BOND and MABEL studies in non Japanese patients.5
In addition a Phase I study in Japanese patients with solid tumors assessed the safety and pharmacokinetic profile of Erbitux as a single agent.6 Results showed that Erbitux is well tolerated as a single agent in Japanese patients.6
“Merck Serono is very pleased to be able to bring this valuable treatment option to patients and physicians in Japan, and to help to improve outcomes for cancer sufferers," said Wayne Paterson, President of Merck Serono Japan.
In Japan, the incidence of CRC has increased markedly during the last 50 years7 with currently around 95,651 cases every year.8 It has become the most common cancer among women and the second most common among men, after stomach cancer.8 Colorectal cancer is the third-leading cause of cancer mortality in Japan, accounting for around one in seven cancer deaths8 – a figure which is in part related to the number of people who first present with metastatic CRC (approximately 25% of patients).9
Erbitux was first approved for the treatment of mCRC in Switzerland in December 2003. It was approved for use in the United States by the FDA in February 2004, followed by EMEA approval for Europe in June 2004. The development of Erbitux in Japan was based on a collaborative effort between Merck KGaA, ImClone Systems Inc., Bristol-Myers Squibb Company, Merck Ltd. Japan and Bristol-Myers K.K.
*Original Label Text:
Erbitux is approved for EGFR-positive curatively unresectable advanced or recurrent colorectal cancer
*Precautions in use on indication:
(1) The efficacy and safety of adjuvant setting of Erbitux has not been established.
(2) The efficacy and safety of first-line setting of Erbitux have not been established.
(3) In order to determine the target population, it is advisable to become acquainted with CLINICAL STUDY RESULTS, as well as the efficacy and safety of Erbitux.
References:
1. Jonker DJ, O’Callaghan CJ, Karapetis CS et al. NEJM 2007; 357: 2040-2048.
2. Scheithauer W, Sobrero A, Lenz HJ et al. ECCO 2007.
3. Cunningham D, Humblet Y, Siena S, et al. N Engl J Med 2004;22;351(4):337-45.
4. Wilke H, Glynne-Jones R, Thaler J, et al. J Clin Oncol 2006; 24(18S):Abstract 3549.
5. Data on File.
6. Yasui H, Shirao K, Yamamoto N, et al. ASCO 2005, abstract # 3209.
7. Koyama Y and Kotake K. Dis Colon Rectum. 1997; 40: S2-9.
8. http://www-dep.iarc.fr/ (Globocan 2002).
9. Cunningham D and Findlay M. Eur J Cancer 1993; 29A: 2007–79.
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 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: 61
