THOUSAND OAKS, CA, USA I February 27, 2015 I Amgen (NASDAQ: AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the marketing authorization for Vectibix® (panitumumab) to include combination with FOLFIRI (an irinotecan-based chemotherapy) as first-line treatment in adult patients with wild-type RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have wild-type RAS tumors.1
“Adding Vectibix to chemotherapy as first-line treatment in patients with wild-type RAS metastatic colorectal cancer has been shown to result in better responses than chemotherapy alone,” said Elliott M. Levy, M.D., senior vice president of Global Development at Amgen. “The CHMP recommendation is an important step toward increasing the treatment options for patients with this aggressive disease and helping improve outcomes in the European Union.”
The new indication is based upon the 20060314 study, which evaluated Vectibix plus FOLFIRI in the first-line setting. Vectibix is already approved in the European Union (EU) for the treatment of adult patients with wild-type RAS mCRC1:
- in first-line in combination with FOLFOX.
- in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
- as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The CHMP positive opinion will now be ratified by the European Commission who, should they affirm the CHMP opinion, will extend the centralized marketing authorization which is valid in the 28 countries that are members of the EU, as well as European Economic Area members, Iceland, Lichtenstein and Norway.
The safety profile of Vectibix was consistent with previously reported studies.
Colorectal cancer is the third most common cancer worldwide, with approximately 1.2 million cases expected to occur globally.2,3 The highest estimated mortality rates associated with colorectal cancer occur in Central and Eastern Europe.3
About Vectibix® (panitumumab)
In the EU, Vectibix is currently indicated for the treatment of adult patients with wild-type RAS mCRC:
- in first-line in combination with FOLFOX.
- in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
- as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
Important EU Product Safety Information
Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFr) inhibitors, are experienced with nearly all patients (approximately 90 percent) treated with Vectibix. The majority of dermatological reactions are mild to moderate in nature. In clinical studies, subsequent to the development of severe dermatological reactions (including stomatitis), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated.
Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC as determined by an FDA-approved test for this use:
- As first-line therapy in combination with FOLFOX
- As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown. Vectibix in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.
RAS is defined as exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereon is referred to as “RAS.”
WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90 percent of patients and were severe (NCI-CTC grade 3 or higher) in 15 percent of patients receiving Vectibix monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. A predefined retrospective subset analysis of Study 3 further identified a shortening of progression-free survival (PFS) and overall survival (OS) in patients with RAS-mutant tumors who received Vectibix® and FOLFOX versus FOLFOX alone. Determination of RAS-mutant tumor status should be performed by an experienced laboratory.
Determination of KRAS mutational status in colorectal tumors using an FDA-approved test indicated for this use is necessary for selection of patients for treatment with Vectibix. Patients with KRAS-mutant mCRC tumors receiving Vectibix in combination with FOLFOX experienced shorter OS compared to FOLFOX alone.
Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment.
In a clinical trial, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4).
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
Fatal and non-fatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms, interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.
The most common adverse reactions of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. The most frequently reported serious, adverse reactions of Vectibix are general physical health deterioration, and intestinal obstruction.
The most commonly reported adverse reactions (≥ 20%) in patients with wild-type KRAS mCRC receiving Vectibix (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) in Study 3 were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. Serious adverse reactions (≥ 2% difference between treatment arms) in Vectibix-treated patients with wild-type KRAS mCRC were diarrhea and dehydration.
To see the full Vectibix Safety Information, visit www.vectibix.com.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
SOURCE: Amgen
Post Views: 207
THOUSAND OAKS, CA, USA I February 27, 2015 I Amgen (NASDAQ: AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the marketing authorization for Vectibix® (panitumumab) to include combination with FOLFIRI (an irinotecan-based chemotherapy) as first-line treatment in adult patients with wild-type RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have wild-type RAS tumors.1
“Adding Vectibix to chemotherapy as first-line treatment in patients with wild-type RAS metastatic colorectal cancer has been shown to result in better responses than chemotherapy alone,” said Elliott M. Levy, M.D., senior vice president of Global Development at Amgen. “The CHMP recommendation is an important step toward increasing the treatment options for patients with this aggressive disease and helping improve outcomes in the European Union.”
The new indication is based upon the 20060314 study, which evaluated Vectibix plus FOLFIRI in the first-line setting. Vectibix is already approved in the European Union (EU) for the treatment of adult patients with wild-type RAS mCRC1:
- in first-line in combination with FOLFOX.
- in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
- as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The CHMP positive opinion will now be ratified by the European Commission who, should they affirm the CHMP opinion, will extend the centralized marketing authorization which is valid in the 28 countries that are members of the EU, as well as European Economic Area members, Iceland, Lichtenstein and Norway.
The safety profile of Vectibix was consistent with previously reported studies.
Colorectal cancer is the third most common cancer worldwide, with approximately 1.2 million cases expected to occur globally.2,3 The highest estimated mortality rates associated with colorectal cancer occur in Central and Eastern Europe.3
About Vectibix® (panitumumab)
In the EU, Vectibix is currently indicated for the treatment of adult patients with wild-type RAS mCRC:
- in first-line in combination with FOLFOX.
- in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
- as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
Important EU Product Safety Information
Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFr) inhibitors, are experienced with nearly all patients (approximately 90 percent) treated with Vectibix. The majority of dermatological reactions are mild to moderate in nature. In clinical studies, subsequent to the development of severe dermatological reactions (including stomatitis), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated.
Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC as determined by an FDA-approved test for this use:
- As first-line therapy in combination with FOLFOX
- As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown. Vectibix in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.
RAS is defined as exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereon is referred to as “RAS.”
WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90 percent of patients and were severe (NCI-CTC grade 3 or higher) in 15 percent of patients receiving Vectibix monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. A predefined retrospective subset analysis of Study 3 further identified a shortening of progression-free survival (PFS) and overall survival (OS) in patients with RAS-mutant tumors who received Vectibix® and FOLFOX versus FOLFOX alone. Determination of RAS-mutant tumor status should be performed by an experienced laboratory.
Determination of KRAS mutational status in colorectal tumors using an FDA-approved test indicated for this use is necessary for selection of patients for treatment with Vectibix. Patients with KRAS-mutant mCRC tumors receiving Vectibix in combination with FOLFOX experienced shorter OS compared to FOLFOX alone.
Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment.
In a clinical trial, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4).
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
Fatal and non-fatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms, interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.
The most common adverse reactions of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. The most frequently reported serious, adverse reactions of Vectibix are general physical health deterioration, and intestinal obstruction.
The most commonly reported adverse reactions (≥ 20%) in patients with wild-type KRAS mCRC receiving Vectibix (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) in Study 3 were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. Serious adverse reactions (≥ 2% difference between treatment arms) in Vectibix-treated patients with wild-type KRAS mCRC were diarrhea and dehydration.
To see the full Vectibix Safety Information, visit www.vectibix.com.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
SOURCE: Amgen
Post Views: 207
