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Inhibitor gets accelerated approval for PTCL
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey. 
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.
The US Food and Drug Administration (FDA) has granted accelerated approval for belinostat (Beleodaq) to treat relapsed or refractory peripheral T-cell lymphoma (PTCL).
Belinostat is a histone deacetylase inhibitor with antineoplastic activity. The drug works by inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis.
The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs.
Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit.
The FDA granted belinostat accelerated approval based on results of a phase 2 trial, which included 129 patients with relapsed or refractory PTCL. All patients received belinostat until disease progression or unacceptable toxicity.
About 26% of patients achieved a complete or partial response. The most common side effects were nausea, fatigue, pyrexia, anemia, and vomiting.
“[Belinostat] is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory PTCL and romidepsin (Istodax) in 2011 for PTCL patients who had received at least 1 prior therapy.
Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.
Mixing meds and supplements to dangerous effect
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
Credit: CDC
A new study indicates that a fair share of patients may be mixing the herbal supplement St. John’s wort with prescribed medications, which can have dangerous results.
St. John’s wort can reduce the concentration of numerous drugs in the body, including anticoagulants and chemotherapeutic agents. And this can result in impaired effectiveness and treatment failure.
But the supplement can also interact with medications to produce serious adverse events.
“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said study author Sarah Taylor, MD, of Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
“And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”
Dr Taylor and her colleagues investigated the use of St. John’s wort and reported their findings in The Journal of Alternative and Complementary Medicine.
To determine how often the supplement was being prescribed or taken with other medications, the researchers conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010.
The team found the use of St. John’s wort in potentially harmful combinations in 28% of the cases reviewed. The drugs involved were warfarin, selective serotonin reuptake inhibitors, benzodiazepines, statins, verapamil, digoxin, and oral contraceptives.
Possible drug interactions include serotonin syndrome (a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in the body), heart disease due to impaired efficacy of blood pressure medications, or unplanned pregnancy due to contraceptive failure, Dr Taylor said.
A key limitation of this study is that only medications recorded by the physician were analyzed. And Dr Taylor said the rate of St. John’s wort interactions may actually be underestimated because the database did not include patients who were using St. John’s wort but did not tell their doctor.
“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Dr Taylor said, adding that France has banned the use of St. John’s wort products, and several other countries, including Japan, the UK, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.
“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”
Company recalls lots of warfarin
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.
Bristol-Myers Squibb has announced a recall of 6 lots of the anticoagulant warfarin, sold as Coumadin for Injection in 5 mg single-use vials, in the US.
The company is recalling these lots after discovering visible particulate matter in unreleased samples of the drug.
The company said the safety risk to patients is likely low and is further mitigated by the product’s prescribing information, which advises that intravenous products be inspected visually before administration.
However, injected particulate metallic and non-metallic cellulose material can cause serious and potentially fatal adverse reactions, such as embolization. Allergic reactions to the foreign material could also occur.
To date, there have been no product complaints or adverse events reported to Bristol-Myers Squibb related to particulate matter in Coumadin for Injection.
Coumadin for Injection was discontinued in early April 2014. The oral formulation of Coumadin is not impacted by this recall.
Coumadin for Injection is packaged in cartons of six 5-mg single-use vials. The affected product includes the following 6 lots distributed to hospitals and pharmacies from November 2011 through January 2014:
Lot # Description NDC Expiration
201125 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2014
201126 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Nov. 2014
201127 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Dec. 2014
201228 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 June 2015
201229 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 July 2015
201230 COUMADIN LINJ 5MG (6VL) US 0590-0324-35 Sept. 2015
Anyone with the aforementioned lots of Coumadin for Injection should stop using or distributing the product and contact Bristol-Myers Squibb’s recall vendor, GENCO, at 1-855-838-5784 to arrange for the return of remaining stock.
Customers with questions about the recall may contact the Bristol-Myers Squibb Customer Information Center at 1-800-332-2056.
Adverse reactions or quality problems associated with the use of this product can be reported to the FDA’s MedWatch Adverse Event Reporting Program.
Ofatumumab falls short in CLL, DLBCL
Credit: Linda Bartlett
The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.
Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.
However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.
CLL trial
In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).
Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.
The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.
The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).
“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”
This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.
“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”
DLBCL trial
The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.
Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.
The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.
There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.
“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.” 
Credit: Linda Bartlett
The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.
Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.
However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.
CLL trial
In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).
Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.
The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.
The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).
“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”
This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.
“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”
DLBCL trial
The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.
Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.
The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.
There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.
“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”
Credit: Linda Bartlett
The anti-CD20 antibody ofatumumab (Arzerra) has failed to meet the primary endpoint in two phase 3 trials, according to the companies developing the drug.
Ofatumumab failed to improve progression-free survival (PFS) when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
Likewise, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
GlaxoSmithKline (GSK) and Genmab recently announced these headline results but said the full analyses of safety and efficacy data are underway and will be completed in the coming months.
However, based on these early results, the companies said they are unlikely to pursue regulatory filings for ofatumumab in either indication.
CLL trial
In the OMB114242 study, researchers enrolled 122 patients with bulky, fludarabine-refractory CLL. Patients were randomized to receive ofatumumab or physicians’ choice (2:1).
Patients randomized to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2000 mg once weekly for 7 weeks, followed 4 weeks later by 1 infusion of 2000 mg every 4 weeks, for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to 6 months.
The primary endpoint was PFS, and secondary objectives were to evaluate response, overall survival, safety, tolerability, and health-related quality of life.
The median PFS, as assessed by an independent review committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (hazard ratio 0.79, P=0.267).
“It was our priority to share this result with the scientific community as soon it became available,” said Rafael Amado, MD, Head of Oncology R&D at GSK. “We will now work to further analyze the data and to better understand the totality of the efficacy and safety findings.”
This study was conducted to meet the requirements from the European Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the European Union and the United States do not include bulky, fludarabine-refractory CLL patients.
“Although ofatumumab performed broadly in line with previous data, today’s result is disappointing,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. “Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population.”
DLBCL trial
The ORCHARRD study included 447 patients who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline or anthracenedione. Patients were also eligible for autologous stem cell transplant.
Patients were randomized 1:1 to receive 3 cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine, and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high-dose chemotherapy followed by transplant.
The primary endpoint was PFS. But GSK and Genmab reported no statistically significant difference in PFS between the treatment arms.
There were no differences in adverse events (AEs) leading to treatment discontinuation, grade 3 or higher AEs, or severe AEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab-plus-chemotherapy arm, which require further analysis.
“We plan to submit detailed data from the ofatumumab ORCHARRD study in DLBCL for presentation at a medical conference later this year, which we hope will provide further clarity on today’s headline results,” Dr van de Winkel said. “Based on [these early] results, we are unlikely to move forward with a regulatory filing.”
FDA warns of VTE related to testosterone products
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) is taking additional action to warn the public about the risk of venous thromboembolism (VTE) associated with the use of testosterone products.
The agency is now requiring manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of VTE these products pose.
The risk is already included in the labeling as a possible consequence of polycythemia, which sometimes occurs with testosterone treatment.
But there have been post-market reports of VTE unrelated to polycythemia.
So the FDA has mandated the label change to provide a more general warning and ensure the risk of VTE is described consistently in the labeling of all approved testosterone products.
This new warning is not related to FDA’s ongoing evaluation of the possible risk of stroke, heart attack, and death in patients taking testosterone products.
The agency is currently evaluating the potential risk of these events, which are described in the Drug Safety Communication posted on January 31, 2014.
Testosterone products are FDA-approved for use in men who lack testosterone or have low testosterone levels in conjunction with an associated medical condition.
The FDA is asking healthcare professionals and consumers to report any adverse reactions related to testosterone products to the agency’s MedWatch Safety Information and Adverse Event Reporting program.
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) is taking additional action to warn the public about the risk of venous thromboembolism (VTE) associated with the use of testosterone products.
The agency is now requiring manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of VTE these products pose.
The risk is already included in the labeling as a possible consequence of polycythemia, which sometimes occurs with testosterone treatment.
But there have been post-market reports of VTE unrelated to polycythemia.
So the FDA has mandated the label change to provide a more general warning and ensure the risk of VTE is described consistently in the labeling of all approved testosterone products.
This new warning is not related to FDA’s ongoing evaluation of the possible risk of stroke, heart attack, and death in patients taking testosterone products.
The agency is currently evaluating the potential risk of these events, which are described in the Drug Safety Communication posted on January 31, 2014.
Testosterone products are FDA-approved for use in men who lack testosterone or have low testosterone levels in conjunction with an associated medical condition.
The FDA is asking healthcare professionals and consumers to report any adverse reactions related to testosterone products to the agency’s MedWatch Safety Information and Adverse Event Reporting program.
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) is taking additional action to warn the public about the risk of venous thromboembolism (VTE) associated with the use of testosterone products.
The agency is now requiring manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of VTE these products pose.
The risk is already included in the labeling as a possible consequence of polycythemia, which sometimes occurs with testosterone treatment.
But there have been post-market reports of VTE unrelated to polycythemia.
So the FDA has mandated the label change to provide a more general warning and ensure the risk of VTE is described consistently in the labeling of all approved testosterone products.
This new warning is not related to FDA’s ongoing evaluation of the possible risk of stroke, heart attack, and death in patients taking testosterone products.
The agency is currently evaluating the potential risk of these events, which are described in the Drug Safety Communication posted on January 31, 2014.
Testosterone products are FDA-approved for use in men who lack testosterone or have low testosterone levels in conjunction with an associated medical condition.
The FDA is asking healthcare professionals and consumers to report any adverse reactions related to testosterone products to the agency’s MedWatch Safety Information and Adverse Event Reporting program.
FDA approves first antihemophilic Fc fusion protein for hemophilia A
The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.
Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.
The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.
The trial included 165 male patients age 12 or older.
Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.
Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.
Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.
None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.
The study was published online in Blood last November.
Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.
Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.
The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.
He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.
The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.
Full prescribing information is available on the drug website.
The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.
Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.
The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.
The trial included 165 male patients age 12 or older.
Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.
Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.
Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.
None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.
The study was published online in Blood last November.
Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.
Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.
The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.
He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.
The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.
Full prescribing information is available on the drug website.
The US Food and Drug Administration (FDA) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Eloctate) to treat children and adults with hemophilia A.
Efmoroctocog alfa is intended to reduce the frequency of injections required to prevent or reduce the occurrence of bleeding in patients with hemophilia A.
The FDA approved efmoroctocog alfa based on results of the phase 3 A-LONG trial, which were reported last year.
The trial included 165 male patients age 12 or older.
Patients who received individualized prophylaxis with efmoroctocog alfa every 3 to 5 days reduced their annualized bleeding rate by 92% compared with patients who received episodic treatment.
Patients who received weekly prophylaxis with efmoroctocog alfa reduced their annualized bleeding rate by 76% compared to patients who received episodic treatment.
Overall, 1 injection of efmoroctocog alfa resolved 87.3% of bleeding episodes.
None of the patients in the study developed neutralizing antibodies, and there were no serious adverse events related to efmoroctocog alfa.
The study was published online in Blood last November.
Efmoroctocog alfa consists of the coagulation factor VIII molecule linked to an Fc protein fragment found in antibodies, which confers the product with a longer half-life than recombinant factor VIII.
Efmoroctocog alfa is specifically indicated for the control and prevention of bleeding episodes, the management of bleeding during surgical procedures, and prophylaxis against bleeding episodes.
The approval of efmoroctocog alfa fills an unmet medical need, according to Johnny Mahlangu, MD, of the Haemophilia Comprehensive Care Centre at the University of Witwatersrand in Johannesburg, South Africa.
He explained that the fusion protein allows patients with hemophilia A to go for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes.
The product, which received orphan drug designation by the FDA, is manufactured by Biogen Idec, Inc, of Cambridge, Massachusetts.
Full prescribing information is available on the drug website.
Voluntary recall of eculizumab issued
Credit: Globovision
The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.
The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.
The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.
All lots in the recall were manufactured using the same process component.
Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.
An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.
Alexion does not anticipate any interruption to the patient supply of eculizumab.
Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.
Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.
For more information on the recall, visit the company website.
Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.
Credit: Globovision
The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.
The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.
The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.
All lots in the recall were manufactured using the same process component.
Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.
An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.
Alexion does not anticipate any interruption to the patient supply of eculizumab.
Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.
Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.
For more information on the recall, visit the company website.
Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.
Credit: Globovision
The manufacturer of the recently approved eculizumab (Soliris) issued a voluntary US recall on June 2 of a single affected lot of the drug, although it included 8 additional lots in the recall.
The manufacturer, Alexion Pharmaceuticals, found visible particulates in the 300 mg/30 mL concentrated solution for intravenous infusion, which could cause an immune reaction and blood clots in patients receiving the drug.
The single affected Soliris lot, distributed in the US only, is #1007A. Also included in the U.S. recall are lots 10002-1, 00006-1, 10003A, 10004A, 10005A, 10005AR, 10006A, and 10008A.
All lots in the recall were manufactured using the same process component.
Alexion believes it has identified the part of the process that has resulted in the visible particles in the solution and has changed the process component.
An earlier recall of eculizumab, also for particulate matter, occurred in December 2013.
Alexion does not anticipate any interruption to the patient supply of eculizumab.
Eculizumab recently received full US Food and Drug Administration (FDA) approval to treat adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS). It had received accelerated approval for this indication in 2011.
Eculizumab is also FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria.
For more information on the recall, visit the company website.
Healthcare professionals and patients should report adverse events or side effects related to Soliris to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.
FDA clears device to treat PE
Credit: Andre E.X. Brown
The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).
The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.
The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.
The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.
“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.
The system produced favorable results in the ULTIMA and SEATTLE II trials.
Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.
The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.
SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.
Credit: Andre E.X. Brown
The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).
The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.
The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.
The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.
“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.
The system produced favorable results in the ULTIMA and SEATTLE II trials.
Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.
The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.
SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.
Credit: Andre E.X. Brown
The US Food and Drug Administration has cleared for marketing a device that facilitates the treatment of pulmonary embolism (PE).
The EkoSonic Endovascular System is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature.
The device is designed to gently accelerate the penetration of thrombolytic agents into thrombi, thereby providing high levels of lysis.
The EkoSonic Endovascular System is the only minimally invasive endovascular therapy that is FDA-cleared for the treatment of PE. The device is manufactured by EKOS Corporation.
“The EKOS clinical data established that patients stricken with a life-threatening pulmonary embolism can be successfully and safely treated with the EkoSonic system,” said Samuel Z. Goldhaber, MD, of Brigham and Woman’s Hospital in Boston, Massachusetts.
The system produced favorable results in the ULTIMA and SEATTLE II trials.
Results of the ULTIMA trial were published in Circulation. The trial showed that, for PE patients at intermediate risk of adverse events, EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications.
The results of SEATTLE II, the prospective, single-arm, multicenter trial of 150 patients, were released at the American College of Cardiology’s 63rd Annual Scientific Session & Expo.
SEATTLE II showed that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves right ventricle function, and decreases pulmonary hypertension.
CHMP recommends ofatumumab for CLL
Credit: Linda Bartlett
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.
The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.
The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.
Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full
approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.
The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.
The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.
Phase 2 study
Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.
Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.
Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m2 for the untreated patients and 70 mg/m2 for relapsed patients.
However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m2, and the relapsed patients were reduced to 50 mg/m2.
The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.
CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.
Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.
This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).
There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of treatment.
Phase 3 study
Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.
Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.
Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.
In both arms, patients received chlorambucil at a dose of 10 mg/m2 orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.
The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.
At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).
Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.
Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.
In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.
Credit: Linda Bartlett
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.
The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.
The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.
Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full
approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.
The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.
The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.
Phase 2 study
Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.
Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.
Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m2 for the untreated patients and 70 mg/m2 for relapsed patients.
However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m2, and the relapsed patients were reduced to 50 mg/m2.
The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.
CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.
Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.
This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).
There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of treatment.
Phase 3 study
Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.
Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.
Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.
In both arms, patients received chlorambucil at a dose of 10 mg/m2 orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.
The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.
At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).
Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.
Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.
In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.
Credit: Linda Bartlett
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for ofatumumab (Arzerra), a monoclonal antibody targeting CD20.
The CHMP is recommending that ofatumumab receive conditional approval for use in combination with chlorambucil or bendamustine to treat patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and are not eligible for fludarabine-based therapy.
The European Commission (EC) will take the CHMP’s opinion into account when deciding whether to approve ofatumumab for this indication.
Ofatumumab already has conditional approval in the Europe Union to treat CLL patients who are refractory to fludarabine and alemtuzumab.
Ofatumumab received conditional approval because the drug’s benefits appear to outweigh the risks it poses. The drug will not receive full
approval until the companies developing ofatumumab, GlaxoSmithKline and Genmab, submit results of additional research to the EC.
The CHMP’s recommendation for expanded approval is based on results from 2 trials in patients with CLL who were ineligible for fludarabine-based treatment.
The first is a phase 2 study (OMB115991) in which researchers evaluated the efficacy of ofatumumab in combination with bendamustine. The second is the phase 3 COMPLEMENT 1 study (OMB110911), a randomized trial in which researchers compared ofatumumab and chlorambucil in combination to chlorambucil alone.
Phase 2 study
Results from this single-arm study were presented at the 2013 International Workshop on CLL. Researchers enrolled 97 patients with CLL, 44 of whom were previously untreated and 53 who had relapsed. The median ages were 62.5 and 68 years, respectively.
Treatment began with acetaminophen, an antihistamine, and a glucocorticoid. Patients then received ofatumumab at 300 mg on day 1 and 1000 mg on day 8 of cycle 1. For cycles 2 through 6, they received 1000 mg on day 1 every 28 days.
Patients received bendamustine on days 1 and 2, every 28 days for up to 6 cycles. The initial dose was 90 mg/m2 for the untreated patients and 70 mg/m2 for relapsed patients.
However, patients required a dose reduction due to toxicity. The previously untreated patients were reduced to 60 mg/m2, and the relapsed patients were reduced to 50 mg/m2.
The overall response rate was 95% in the previously untreated group and 74% in the relapsed group. Complete responses occurred in 43% and 11%, respectively.
CT results showed the overall response rate was 82% in the previously untreated group and 70% in the relapsed group. Complete responses occurred in 27% and 9%, respectively. The median time to response was 0.95 months for both groups.
Grade 3 or higher adverse events occurred in 25% of patients in the previously untreated group and 38% of those in the relapsed group.
This included infusion reactions (11% and 8%, respectively), neutropenia (16% and 29%, respectively), infections (11% and 15%, respectively), rash (2% of previously untreated patients), febrile neutropenia (4% of relapsed patients), and thrombocytopenia (4% of relapsed patients).
There were no deaths in the previously untreated group, but 4 patients died in the relapsed group. Two of these deaths may have been related to study treatment. One patient died of pneumonia and hemolytic anemia 15 days after the last dose of treatment, and 1 patient died of sepsis 4 days after the last dose of treatment.
Phase 3 study
Data from the COMPLEMENT 1 study were presented at ASH 2013. Researchers compared ofatumumab plus chlorambucil to chlorambucil alone in 447 previously untreated patients with CLL who were ineligible for fludarabine-based therapy.
Patients had a median age of 69 years (range, 35 to 92). Seventy-two percent had 2 or more comorbidities, and 48% had a creatinine clearance of less than 70 mL/min.
Patients in the ofatumumab arm received the drug at 300 mg in cycle 1 on day 1, 1000 mg in cycle 1 on day 8, and 1000 mg administered on day 1 of all subsequent 28-day cycles.
In both arms, patients received chlorambucil at a dose of 10 mg/m2 orally on days 1 to 7, every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid.
The overall response rate was 82% in the ofatumumab-chlorambucil group and 69% in the chlorambucil-alone group (P=0.001). Complete response rates were 12% and 1%, respectively.
At a median follow-up of 29 months, the median overall survival was not reached for either treatment arm. However, ofatumumab-treated patients had longer progression-free survival than patients who received chlorambucil alone—22.4 months and 13.1 months, respectively (P<0.001).
Grade 3 or higher adverse events occurred in 50% of ofatumumab-treated patients and 43% of patients who received chlorambucil alone. The most common event was neutropenia, which occurred in 26% and 14% of patients, respectively.
Grade 3 or higher infections occurred in 15% of ofatumumab-treated patients and 14% of patients who received chlorambucil alone. The most common was pneumonia, which occurred in 4% and 3%, respectively.
In the entire cohort, grade 3 or higher infusion-related events occurred in 10% of patients, but there were no fatal infusion reactions. Two percent of subjects in both arms died during treatment.
FDA approves first molecular test for blood typing
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has approved the first molecular assay for determining blood compatibility prior to transfusion.
The Immucor PreciseType Human Erythrocyte Antigen (HEA) Molecular BeadChip Test can be used to determine donor and patient non-ABO/non-RhD red blood cell types.
The test provides an alternative to serological typing and may enhance patient care in certain situations, according to Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The Immucor PreciseType HEA Molecular BeadChip Test works by detecting genes that govern the expression of 36 antigens that can appear on the surface of red blood cells.
The test uses thousands of coded beads that bind with the genes coding for non-ABO red blood cell antigens that are present in a blood sample.
A light signal is generated from each bead that has captured a specific gene. Accompanying computer software decodes the light signals and reports which antigens are predicted to be present on the red cells, based on the genes detected.
Researchers conducted a study to compare the typing results of the PreciseType HEA Molecular BeadChip Test with licensed serological reagents and DNA sequencing. And the results demonstrated comparable performance between the methods.
The product was brought before the FDA’s Blood Products Advisory Committee on March 18, 2014. After reviewing the relevant information, the committee said the data provided reasonable assurance that the Immucor PreciseType HEA Molecular BeadChip Test is safe and effective for its intended use.
The test is manufactured by BioArray Solutions Ltd. of Warren, New Jersey.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has approved the first molecular assay for determining blood compatibility prior to transfusion.
The Immucor PreciseType Human Erythrocyte Antigen (HEA) Molecular BeadChip Test can be used to determine donor and patient non-ABO/non-RhD red blood cell types.
The test provides an alternative to serological typing and may enhance patient care in certain situations, according to Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The Immucor PreciseType HEA Molecular BeadChip Test works by detecting genes that govern the expression of 36 antigens that can appear on the surface of red blood cells.
The test uses thousands of coded beads that bind with the genes coding for non-ABO red blood cell antigens that are present in a blood sample.
A light signal is generated from each bead that has captured a specific gene. Accompanying computer software decodes the light signals and reports which antigens are predicted to be present on the red cells, based on the genes detected.
Researchers conducted a study to compare the typing results of the PreciseType HEA Molecular BeadChip Test with licensed serological reagents and DNA sequencing. And the results demonstrated comparable performance between the methods.
The product was brought before the FDA’s Blood Products Advisory Committee on March 18, 2014. After reviewing the relevant information, the committee said the data provided reasonable assurance that the Immucor PreciseType HEA Molecular BeadChip Test is safe and effective for its intended use.
The test is manufactured by BioArray Solutions Ltd. of Warren, New Jersey.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has approved the first molecular assay for determining blood compatibility prior to transfusion.
The Immucor PreciseType Human Erythrocyte Antigen (HEA) Molecular BeadChip Test can be used to determine donor and patient non-ABO/non-RhD red blood cell types.
The test provides an alternative to serological typing and may enhance patient care in certain situations, according to Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The Immucor PreciseType HEA Molecular BeadChip Test works by detecting genes that govern the expression of 36 antigens that can appear on the surface of red blood cells.
The test uses thousands of coded beads that bind with the genes coding for non-ABO red blood cell antigens that are present in a blood sample.
A light signal is generated from each bead that has captured a specific gene. Accompanying computer software decodes the light signals and reports which antigens are predicted to be present on the red cells, based on the genes detected.
Researchers conducted a study to compare the typing results of the PreciseType HEA Molecular BeadChip Test with licensed serological reagents and DNA sequencing. And the results demonstrated comparable performance between the methods.
The product was brought before the FDA’s Blood Products Advisory Committee on March 18, 2014. After reviewing the relevant information, the committee said the data provided reasonable assurance that the Immucor PreciseType HEA Molecular BeadChip Test is safe and effective for its intended use.
The test is manufactured by BioArray Solutions Ltd. of Warren, New Jersey.