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FDA expands indication for apixaban
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) has approved apixaban (Eliquis) to treat venous thromboembolism (VTE) and prevent recurrent VTE after initial therapy.
Apixaban is an oral selective factor Xa inhibitor that is already FDA approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent VTE in patients who have undergone hip or knee replacement surgery.
Apixaban’s latest FDA approval was based on results of the AMPLIFY and AMPLIFY-EXT studies.
The AMPLIFY trial
AMPLIFY included 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) who required treatment for 6 months. They had a mean age of 56.9 years, and 89.8% of randomized patients had unprovoked VTE.
About half of patients (n=2691) were randomized to receive apixaban at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months.
The other half (n=2704) were randomized to the standard of care—enoxaparin at 1 mg/kg twice daily for at least 5 days until they had an INR ≥ 2 and warfarin (target INR range 2.0-3.0) for 6 months.
Apixaban proved noninferior to standard therapy in the combined primary endpoint of recurrent, symptomatic VTE (nonfatal DVT or PE) or VTE-related death. This outcome occurred in 2.3% of patients in the apixaban arm and 2.7% of patients in the standard-therapy arm (P<0.0001 for noninferiority).
Apixaban also proved superior to standard therapy with regard to bleeding. The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).
The AMPLIFY-EXT trial
AMPLIFY-EXT included 2486 patients who had completed 6 to 12 months of anticoagulation treatment for DVT or PE. Their mean age was 56.7 years, and 91.7% of randomized patients had unprovoked VTE.
Patients were randomized to receive apixaban at 2.5 mg (n=842), apixaban at 5 mg (n=815), or placebo (n=829).
Both apixaban doses were significantly superior to placebo (P<0.001) with regard to the primary efficacy endpoint, which was recurrent VTE or all-cause death.
During the 12-month active study period, these events occurred in 3.8% of patients in the 2.5 mg arm, 4.2% of patients in the 5 mg arm, and 11.6% of patients in the placebo arm.
The primary safety endpoint was the incidence of major bleeding, and there was no significant difference among the treatment arms. Major bleeding occurred in 0.2% of patients in the 2.5 mg arm, 0.1% of patients in the 5 mg arm, and 0.5% of patients in the placebo arm.
Nevertheless, apixaban has been shown to increase the risk of bleeding and can cause serious, potentially fatal, bleeding.
Apixaban’s label includes boxed warnings detailing the increased risk of thrombotic events in patients who prematurely discontinue the drug, as well as the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients undergoing spinal epidural anesthesia or spinal puncture.
For more information, visit eliquis.com. The drug is under joint development by Pfizer and Bristol-Myers Squibb. 
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) has approved apixaban (Eliquis) to treat venous thromboembolism (VTE) and prevent recurrent VTE after initial therapy.
Apixaban is an oral selective factor Xa inhibitor that is already FDA approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent VTE in patients who have undergone hip or knee replacement surgery.
Apixaban’s latest FDA approval was based on results of the AMPLIFY and AMPLIFY-EXT studies.
The AMPLIFY trial
AMPLIFY included 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) who required treatment for 6 months. They had a mean age of 56.9 years, and 89.8% of randomized patients had unprovoked VTE.
About half of patients (n=2691) were randomized to receive apixaban at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months.
The other half (n=2704) were randomized to the standard of care—enoxaparin at 1 mg/kg twice daily for at least 5 days until they had an INR ≥ 2 and warfarin (target INR range 2.0-3.0) for 6 months.
Apixaban proved noninferior to standard therapy in the combined primary endpoint of recurrent, symptomatic VTE (nonfatal DVT or PE) or VTE-related death. This outcome occurred in 2.3% of patients in the apixaban arm and 2.7% of patients in the standard-therapy arm (P<0.0001 for noninferiority).
Apixaban also proved superior to standard therapy with regard to bleeding. The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).
The AMPLIFY-EXT trial
AMPLIFY-EXT included 2486 patients who had completed 6 to 12 months of anticoagulation treatment for DVT or PE. Their mean age was 56.7 years, and 91.7% of randomized patients had unprovoked VTE.
Patients were randomized to receive apixaban at 2.5 mg (n=842), apixaban at 5 mg (n=815), or placebo (n=829).
Both apixaban doses were significantly superior to placebo (P<0.001) with regard to the primary efficacy endpoint, which was recurrent VTE or all-cause death.
During the 12-month active study period, these events occurred in 3.8% of patients in the 2.5 mg arm, 4.2% of patients in the 5 mg arm, and 11.6% of patients in the placebo arm.
The primary safety endpoint was the incidence of major bleeding, and there was no significant difference among the treatment arms. Major bleeding occurred in 0.2% of patients in the 2.5 mg arm, 0.1% of patients in the 5 mg arm, and 0.5% of patients in the placebo arm.
Nevertheless, apixaban has been shown to increase the risk of bleeding and can cause serious, potentially fatal, bleeding.
Apixaban’s label includes boxed warnings detailing the increased risk of thrombotic events in patients who prematurely discontinue the drug, as well as the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients undergoing spinal epidural anesthesia or spinal puncture.
For more information, visit eliquis.com. The drug is under joint development by Pfizer and Bristol-Myers Squibb.
Credit: Kevin MacKenzie
The US Food and Drug Administration (FDA) has approved apixaban (Eliquis) to treat venous thromboembolism (VTE) and prevent recurrent VTE after initial therapy.
Apixaban is an oral selective factor Xa inhibitor that is already FDA approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent VTE in patients who have undergone hip or knee replacement surgery.
Apixaban’s latest FDA approval was based on results of the AMPLIFY and AMPLIFY-EXT studies.
The AMPLIFY trial
AMPLIFY included 5395 patients with confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) who required treatment for 6 months. They had a mean age of 56.9 years, and 89.8% of randomized patients had unprovoked VTE.
About half of patients (n=2691) were randomized to receive apixaban at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months.
The other half (n=2704) were randomized to the standard of care—enoxaparin at 1 mg/kg twice daily for at least 5 days until they had an INR ≥ 2 and warfarin (target INR range 2.0-3.0) for 6 months.
Apixaban proved noninferior to standard therapy in the combined primary endpoint of recurrent, symptomatic VTE (nonfatal DVT or PE) or VTE-related death. This outcome occurred in 2.3% of patients in the apixaban arm and 2.7% of patients in the standard-therapy arm (P<0.0001 for noninferiority).
Apixaban also proved superior to standard therapy with regard to bleeding. The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).
The AMPLIFY-EXT trial
AMPLIFY-EXT included 2486 patients who had completed 6 to 12 months of anticoagulation treatment for DVT or PE. Their mean age was 56.7 years, and 91.7% of randomized patients had unprovoked VTE.
Patients were randomized to receive apixaban at 2.5 mg (n=842), apixaban at 5 mg (n=815), or placebo (n=829).
Both apixaban doses were significantly superior to placebo (P<0.001) with regard to the primary efficacy endpoint, which was recurrent VTE or all-cause death.
During the 12-month active study period, these events occurred in 3.8% of patients in the 2.5 mg arm, 4.2% of patients in the 5 mg arm, and 11.6% of patients in the placebo arm.
The primary safety endpoint was the incidence of major bleeding, and there was no significant difference among the treatment arms. Major bleeding occurred in 0.2% of patients in the 2.5 mg arm, 0.1% of patients in the 5 mg arm, and 0.5% of patients in the placebo arm.
Nevertheless, apixaban has been shown to increase the risk of bleeding and can cause serious, potentially fatal, bleeding.
Apixaban’s label includes boxed warnings detailing the increased risk of thrombotic events in patients who prematurely discontinue the drug, as well as the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients undergoing spinal epidural anesthesia or spinal puncture.
For more information, visit eliquis.com. The drug is under joint development by Pfizer and Bristol-Myers Squibb.
NICE supports lenalidomide for MDS
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.
Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.
However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.
In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.
But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.
Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.
“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.
“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”
This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.
Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.
The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.
However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.
Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.
However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.
In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.
But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.
Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.
“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.
“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”
This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.
Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.
The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.
However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending lenalidomide (Revlimid) as an option for treating myelodysplastic syndromes (MDS) characterized by 5q deletion.
Lenalidomide is approved in the European Union to treat transfusion-dependent anemia caused by low- or intermediate-1 risk MDS characterized by 5q deletion when other therapeutic options are insufficient or inadequate.
However, the main treatment option for this patient population in the UK is best supportive care, which involves regular red blood cell transfusions.
In earlier draft guidances, NICE did not support lenalidomide use in MDS patients with 5q deletion. Although data suggested the drug is effective for these patients, a NICE advisory committee was not convinced the drug provided a survival benefit.
But now, the committee has concluded that lenalidomide is a clinically effective treatment for these patients because it is associated with a statistically significant improvement in transfusion independence and health-related quality of life compared with placebo.
Furthermore, the committee said it is plausible that lenalidomide can indirectly improve overall survival by improving transfusion independence.
“The committee heard from clinical experts that lenalidomide is an effective therapy,” said Sir Andrew Dillon, NICE chief executive.
“Celgene–who market lenalidomide–worked with us to provide enough evidence to make it possible for us to recommend it for this group of people. Celgene provided a revised analysis and further information on their proposal for a reduction in the cost of the drug to the NHS [National Health Service].”
This patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. And Celgene will provide the drug free of charge for those people who receive more than 26 monthly cycles.
Lenalidomide is available in 21-day packs of 10 mg and 5 mg capsules at net prices of £3780 and £3570, respectively. The cost of a 28-day cycle of treatment with 10 mg of lenalidomide (excluding value-added tax) is £3780.
The committee noted that the incremental cost-effectiveness ratio for lenalidomide compared with best supportive care is uncertain because the proportion of people who might need treatment beyond 26 cycles is uncertain.
However, the committee accepted that a commitment from Celgene to publish data on the proportion of people receiving treatment beyond 26 cycles would provide reassurance that lenalidomide is a cost-effective use of NHS resources in MDS patients with 5q deletion.
NICE’s final draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Rise of new anticoagulants means higher costs
Credit: CDC
A new study suggests the use of novel oral anticoagulants (NOACs) has surpassed warfarin use in the last few years, but the cost burden for NOACs is much higher than that of warfarin.
By mid-2013, the NOACs dabigatran, rivaroxaban, and apixaban accounted for 62% of all new anticoagulant prescriptions included in the study, but this represented 98% of the total anticoagulant costs.
These findings and a related commentary appear in The American Journal of Medicine.
NOAC use on the rise
To better understand NOAC use, researchers analyzed medical and prescription claims data from the insurance company Aetna. They identified 6893 patients with atrial fibrillation (AF) who were prescribed an oral anticoagulant from 2010 to 2013.
During that time, 45,472 anticoagulant prescriptions were filled—26,253 (57.7%) for warfarin, 14,922 (32.8%) for dabigatran, 4241 (9.3%) for rivaroxaban, and 56 (0.1%) for apixaban.
The researchers noted that the US Food and Drug Administration (FDA) approved dabigatran for use in AF patients in October 2010. And by October 2011, patients were as likely to receive dabigatran as warfarin.
Rivaroxaban was FDA-approved for AF in November 2011, and, by June 2013, the drug had overtaken both warfarin and dabigatran. Apixaban use increased the least, as the drug gained FDA approval for AF in December 2012.
Though NOACs appeared to be on the rise overall, the researchers found NOAC use was significantly less likely for women, patients living in lower income areas, and patients with higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores (P<0.001 for each variable).
The team said this finding is significant because, in the clinical trials supporting NOAC approvals, most patients had CHADS2/CHA2DS2-VASC scores in the higher ranges.
“The greatest absolute benefit from novel anticoagulants has been shown in clinical trials to be among patients at highest baseline risk for stroke or systemic embolization,” said lead investigator Niteesh K. Choudhry, MD, PhD, of Brigham and Women’s Hospital in Boston.
“[This] is at odds with our observation of [physicians selecting] seemingly lower-risk patients for these drugs. Such a finding may reflect provider conservatism for new drug adoption, particularly given longitudinal experience with warfarin.”
Higher costs
Dr Choudhry and his colleagues also found that NOACs confer high healthcare cost consequences. The data revealed that NOACs represented 98% of the total dollars spent on anticoagulants from 2010 to 2013.
Over the first 6 months, the average combined patient and insurer cost associated with starting a NOAC was $900 greater than the cost of starting warfarin.
“Average patient out-of-pocket and insurance spending was more than 5-fold and 15-fold higher, respectively, for novel anticoagulants as compared with warfarin,” Dr Choudhry said. “A 6-month difference in total costs of $900 in our cohort translates into billions of dollars at a national level.”
Taking their findings together, the researchers said this study suggests more information may be needed to fully understand the implications of rising NOAC prescriptions.
“These findings point to the need to conduct ongoing surveillance of the adoption of new agents into clinical practice,” Dr Choudhry said, “as well as the need for robust, real-world comparative-effectiveness analyses of these medications, to enable patients and providers to make informed decisions about their relative benefit, safety, and cost-effectiveness.”
Credit: CDC
A new study suggests the use of novel oral anticoagulants (NOACs) has surpassed warfarin use in the last few years, but the cost burden for NOACs is much higher than that of warfarin.
By mid-2013, the NOACs dabigatran, rivaroxaban, and apixaban accounted for 62% of all new anticoagulant prescriptions included in the study, but this represented 98% of the total anticoagulant costs.
These findings and a related commentary appear in The American Journal of Medicine.
NOAC use on the rise
To better understand NOAC use, researchers analyzed medical and prescription claims data from the insurance company Aetna. They identified 6893 patients with atrial fibrillation (AF) who were prescribed an oral anticoagulant from 2010 to 2013.
During that time, 45,472 anticoagulant prescriptions were filled—26,253 (57.7%) for warfarin, 14,922 (32.8%) for dabigatran, 4241 (9.3%) for rivaroxaban, and 56 (0.1%) for apixaban.
The researchers noted that the US Food and Drug Administration (FDA) approved dabigatran for use in AF patients in October 2010. And by October 2011, patients were as likely to receive dabigatran as warfarin.
Rivaroxaban was FDA-approved for AF in November 2011, and, by June 2013, the drug had overtaken both warfarin and dabigatran. Apixaban use increased the least, as the drug gained FDA approval for AF in December 2012.
Though NOACs appeared to be on the rise overall, the researchers found NOAC use was significantly less likely for women, patients living in lower income areas, and patients with higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores (P<0.001 for each variable).
The team said this finding is significant because, in the clinical trials supporting NOAC approvals, most patients had CHADS2/CHA2DS2-VASC scores in the higher ranges.
“The greatest absolute benefit from novel anticoagulants has been shown in clinical trials to be among patients at highest baseline risk for stroke or systemic embolization,” said lead investigator Niteesh K. Choudhry, MD, PhD, of Brigham and Women’s Hospital in Boston.
“[This] is at odds with our observation of [physicians selecting] seemingly lower-risk patients for these drugs. Such a finding may reflect provider conservatism for new drug adoption, particularly given longitudinal experience with warfarin.”
Higher costs
Dr Choudhry and his colleagues also found that NOACs confer high healthcare cost consequences. The data revealed that NOACs represented 98% of the total dollars spent on anticoagulants from 2010 to 2013.
Over the first 6 months, the average combined patient and insurer cost associated with starting a NOAC was $900 greater than the cost of starting warfarin.
“Average patient out-of-pocket and insurance spending was more than 5-fold and 15-fold higher, respectively, for novel anticoagulants as compared with warfarin,” Dr Choudhry said. “A 6-month difference in total costs of $900 in our cohort translates into billions of dollars at a national level.”
Taking their findings together, the researchers said this study suggests more information may be needed to fully understand the implications of rising NOAC prescriptions.
“These findings point to the need to conduct ongoing surveillance of the adoption of new agents into clinical practice,” Dr Choudhry said, “as well as the need for robust, real-world comparative-effectiveness analyses of these medications, to enable patients and providers to make informed decisions about their relative benefit, safety, and cost-effectiveness.”
Credit: CDC
A new study suggests the use of novel oral anticoagulants (NOACs) has surpassed warfarin use in the last few years, but the cost burden for NOACs is much higher than that of warfarin.
By mid-2013, the NOACs dabigatran, rivaroxaban, and apixaban accounted for 62% of all new anticoagulant prescriptions included in the study, but this represented 98% of the total anticoagulant costs.
These findings and a related commentary appear in The American Journal of Medicine.
NOAC use on the rise
To better understand NOAC use, researchers analyzed medical and prescription claims data from the insurance company Aetna. They identified 6893 patients with atrial fibrillation (AF) who were prescribed an oral anticoagulant from 2010 to 2013.
During that time, 45,472 anticoagulant prescriptions were filled—26,253 (57.7%) for warfarin, 14,922 (32.8%) for dabigatran, 4241 (9.3%) for rivaroxaban, and 56 (0.1%) for apixaban.
The researchers noted that the US Food and Drug Administration (FDA) approved dabigatran for use in AF patients in October 2010. And by October 2011, patients were as likely to receive dabigatran as warfarin.
Rivaroxaban was FDA-approved for AF in November 2011, and, by June 2013, the drug had overtaken both warfarin and dabigatran. Apixaban use increased the least, as the drug gained FDA approval for AF in December 2012.
Though NOACs appeared to be on the rise overall, the researchers found NOAC use was significantly less likely for women, patients living in lower income areas, and patients with higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores (P<0.001 for each variable).
The team said this finding is significant because, in the clinical trials supporting NOAC approvals, most patients had CHADS2/CHA2DS2-VASC scores in the higher ranges.
“The greatest absolute benefit from novel anticoagulants has been shown in clinical trials to be among patients at highest baseline risk for stroke or systemic embolization,” said lead investigator Niteesh K. Choudhry, MD, PhD, of Brigham and Women’s Hospital in Boston.
“[This] is at odds with our observation of [physicians selecting] seemingly lower-risk patients for these drugs. Such a finding may reflect provider conservatism for new drug adoption, particularly given longitudinal experience with warfarin.”
Higher costs
Dr Choudhry and his colleagues also found that NOACs confer high healthcare cost consequences. The data revealed that NOACs represented 98% of the total dollars spent on anticoagulants from 2010 to 2013.
Over the first 6 months, the average combined patient and insurer cost associated with starting a NOAC was $900 greater than the cost of starting warfarin.
“Average patient out-of-pocket and insurance spending was more than 5-fold and 15-fold higher, respectively, for novel anticoagulants as compared with warfarin,” Dr Choudhry said. “A 6-month difference in total costs of $900 in our cohort translates into billions of dollars at a national level.”
Taking their findings together, the researchers said this study suggests more information may be needed to fully understand the implications of rising NOAC prescriptions.
“These findings point to the need to conduct ongoing surveillance of the adoption of new agents into clinical practice,” Dr Choudhry said, “as well as the need for robust, real-world comparative-effectiveness analyses of these medications, to enable patients and providers to make informed decisions about their relative benefit, safety, and cost-effectiveness.”
DOJ closes investigation of PLATO trial
Credit: AstraZeneca
The US Department of Justice (DOJ) is closing its investigation of PLATO, a clinical trial of the antiplatelet agent ticagrelor (Brilinta), according to the drug’s developer, AstraZeneca.
The company also said the government is not planning any further action.
The DOJ began its investigation in October 2013, issuing a civil investigative demand requiring AstraZeneca to provide the department with documents and information related to the PLATO trial.
The trial compared ticagrelor to the antiplatelet agent clopidogrel in 18,624 patients with acute coronary syndromes (ACS), with or without ST-segment elevation.
The results suggested that ticagrelor significantly reduced the rate of myocardial infarction and death from any cause, although it did not decrease the risk of stroke. Ticagrelor did not increase the rate of overall bleeding, but it did increase the rate of bleeding not related to procedures.
These results led to ticagrelor’s approval in the US and more than 100 other countries. But members of the medical community questioned PLATO’s results, with some even suggesting the possibility of trial misconduct.
So the DOJ launched its investigation. The details of the inquiry are unclear, but AstraZeneca said it “focused on questions that have been raised previously in public about the trial.”
Many of those questions have been raised in the International Journal of Cardiology, in articles by Victor Serebruany, MD, PhD, of HeartDrug Research Laboratories in Towson, Maryland, and James DiNicolantonio, PharmD, of Wegmans Pharmacy in Ithaca, New York.
In the years since PLATO’s results were first published, Drs DiNicolantonio and Serebruany have pointed out differences between trial data published in the NEJM paper and FDA reviews of the data, noted the geographic discrepancies in results observed with ticagrelor, and raised questions about site monitoring, blinding practices, and patient deaths, among other issues.
PLATO investigators addressed these questions and allegations in an article of their own, which appeared in the International Journal of Cardiology in December 2013. The overall message was that PLATO’s results are valid.
“We have always had absolute confidence in the integrity of the PLATO trial, and we are proud of the important benefit [ticagrelor] offers to patients around the world suffering from acute coronary syndrome,” said Pascal Soriot, AstraZeneca’s Chief Executive Officer.
As for the future of ticagrelor, AstraZeneca recently announced the start of the SOCRATES trial, a study of the drug for patients with acute ischemic stroke or transient ischemic attack, and the THEMIS study in patients with type 2 diabetes and coronary atherosclerosis.
These studies form part of PARTHENON, a trial program involving more than 80,000 patients worldwide. The program also includes 2 trials that have recently completed recruitment—EUCLID, a study of patients with peripheral artery disease and PEGASUS, a study of ticagrelor for secondary prevention in patients with previous myocardial infarction.
AstraZeneca expects headline results from PEGASUS to be available in the first quarter of 2015.
Credit: AstraZeneca
The US Department of Justice (DOJ) is closing its investigation of PLATO, a clinical trial of the antiplatelet agent ticagrelor (Brilinta), according to the drug’s developer, AstraZeneca.
The company also said the government is not planning any further action.
The DOJ began its investigation in October 2013, issuing a civil investigative demand requiring AstraZeneca to provide the department with documents and information related to the PLATO trial.
The trial compared ticagrelor to the antiplatelet agent clopidogrel in 18,624 patients with acute coronary syndromes (ACS), with or without ST-segment elevation.
The results suggested that ticagrelor significantly reduced the rate of myocardial infarction and death from any cause, although it did not decrease the risk of stroke. Ticagrelor did not increase the rate of overall bleeding, but it did increase the rate of bleeding not related to procedures.
These results led to ticagrelor’s approval in the US and more than 100 other countries. But members of the medical community questioned PLATO’s results, with some even suggesting the possibility of trial misconduct.
So the DOJ launched its investigation. The details of the inquiry are unclear, but AstraZeneca said it “focused on questions that have been raised previously in public about the trial.”
Many of those questions have been raised in the International Journal of Cardiology, in articles by Victor Serebruany, MD, PhD, of HeartDrug Research Laboratories in Towson, Maryland, and James DiNicolantonio, PharmD, of Wegmans Pharmacy in Ithaca, New York.
In the years since PLATO’s results were first published, Drs DiNicolantonio and Serebruany have pointed out differences between trial data published in the NEJM paper and FDA reviews of the data, noted the geographic discrepancies in results observed with ticagrelor, and raised questions about site monitoring, blinding practices, and patient deaths, among other issues.
PLATO investigators addressed these questions and allegations in an article of their own, which appeared in the International Journal of Cardiology in December 2013. The overall message was that PLATO’s results are valid.
“We have always had absolute confidence in the integrity of the PLATO trial, and we are proud of the important benefit [ticagrelor] offers to patients around the world suffering from acute coronary syndrome,” said Pascal Soriot, AstraZeneca’s Chief Executive Officer.
As for the future of ticagrelor, AstraZeneca recently announced the start of the SOCRATES trial, a study of the drug for patients with acute ischemic stroke or transient ischemic attack, and the THEMIS study in patients with type 2 diabetes and coronary atherosclerosis.
These studies form part of PARTHENON, a trial program involving more than 80,000 patients worldwide. The program also includes 2 trials that have recently completed recruitment—EUCLID, a study of patients with peripheral artery disease and PEGASUS, a study of ticagrelor for secondary prevention in patients with previous myocardial infarction.
AstraZeneca expects headline results from PEGASUS to be available in the first quarter of 2015.
Credit: AstraZeneca
The US Department of Justice (DOJ) is closing its investigation of PLATO, a clinical trial of the antiplatelet agent ticagrelor (Brilinta), according to the drug’s developer, AstraZeneca.
The company also said the government is not planning any further action.
The DOJ began its investigation in October 2013, issuing a civil investigative demand requiring AstraZeneca to provide the department with documents and information related to the PLATO trial.
The trial compared ticagrelor to the antiplatelet agent clopidogrel in 18,624 patients with acute coronary syndromes (ACS), with or without ST-segment elevation.
The results suggested that ticagrelor significantly reduced the rate of myocardial infarction and death from any cause, although it did not decrease the risk of stroke. Ticagrelor did not increase the rate of overall bleeding, but it did increase the rate of bleeding not related to procedures.
These results led to ticagrelor’s approval in the US and more than 100 other countries. But members of the medical community questioned PLATO’s results, with some even suggesting the possibility of trial misconduct.
So the DOJ launched its investigation. The details of the inquiry are unclear, but AstraZeneca said it “focused on questions that have been raised previously in public about the trial.”
Many of those questions have been raised in the International Journal of Cardiology, in articles by Victor Serebruany, MD, PhD, of HeartDrug Research Laboratories in Towson, Maryland, and James DiNicolantonio, PharmD, of Wegmans Pharmacy in Ithaca, New York.
In the years since PLATO’s results were first published, Drs DiNicolantonio and Serebruany have pointed out differences between trial data published in the NEJM paper and FDA reviews of the data, noted the geographic discrepancies in results observed with ticagrelor, and raised questions about site monitoring, blinding practices, and patient deaths, among other issues.
PLATO investigators addressed these questions and allegations in an article of their own, which appeared in the International Journal of Cardiology in December 2013. The overall message was that PLATO’s results are valid.
“We have always had absolute confidence in the integrity of the PLATO trial, and we are proud of the important benefit [ticagrelor] offers to patients around the world suffering from acute coronary syndrome,” said Pascal Soriot, AstraZeneca’s Chief Executive Officer.
As for the future of ticagrelor, AstraZeneca recently announced the start of the SOCRATES trial, a study of the drug for patients with acute ischemic stroke or transient ischemic attack, and the THEMIS study in patients with type 2 diabetes and coronary atherosclerosis.
These studies form part of PARTHENON, a trial program involving more than 80,000 patients worldwide. The program also includes 2 trials that have recently completed recruitment—EUCLID, a study of patients with peripheral artery disease and PEGASUS, a study of ticagrelor for secondary prevention in patients with previous myocardial infarction.
AstraZeneca expects headline results from PEGASUS to be available in the first quarter of 2015.
MM drug disappoints in phase 3 trial
The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.
Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).
This result raises questions about carfilzomib’s chances for regulatory approval around the world.
However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.
At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.
That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.
The FOCUS trial
For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.
Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.
Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.
The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.
However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.
Full prescribing information for carfilzomib is available at www.kyprolis.com.
Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.
The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.
Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).
This result raises questions about carfilzomib’s chances for regulatory approval around the world.
However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.
At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.
That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.
The FOCUS trial
For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.
Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.
Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.
The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.
However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.
Full prescribing information for carfilzomib is available at www.kyprolis.com.
Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.
The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.
Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).
This result raises questions about carfilzomib’s chances for regulatory approval around the world.
However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.
At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.
That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.
The FOCUS trial
For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.
Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.
Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.
The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.
However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.
Full prescribing information for carfilzomib is available at www.kyprolis.com.
Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.
Drug on the fast track to treat AML
Credit: Esther Dyson
The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).
AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.
Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.
AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.
Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Phase 1 trial results
Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).
The trial included 35 patients with a median age of 68 years (range, 48-81).
Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.
The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.
The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).
Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.
Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.
The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.
Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.
This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.
Credit: Esther Dyson
The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).
AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.
Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.
AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.
Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Phase 1 trial results
Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).
The trial included 35 patients with a median age of 68 years (range, 48-81).
Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.
The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.
The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).
Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.
Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.
The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.
Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.
This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.
Credit: Esther Dyson
The US Food and Drug Administration (FDA) has granted fast track designation for AG-221 to treat acute myelogenous leukemia (AML) patients with mutated isocitrate dehydrogenase-2 (IDH2).
AG-221 is an IDH2 inhibitor under evaluation in a phase 1 trial of patients with advanced hematologic malignancies.
Results from this trial were presented at the 19th Congress of the European Hematology Association, which took place in Milan in June.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of a new drug application (NDA) for drugs with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates meetings between the FDA and the company developing a drug to discuss all aspects of development to support approval. It also affords the developer the opportunity to submit sections of an NDA on a rolling basis as data become available, so the FDA does not have wait for the entire NDA submission before beginning its review.
AG-221 also recently received orphan designation as a treatment for AML. The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders that affect fewer than 200,000 people in the US.
Orphan designation affords the drug’s developer certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Phase 1 trial results
Thus far in the phase 1 study, AG-221 has proven active and well-tolerated in patients with AML, myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML).
The trial included 35 patients with a median age of 68 years (range, 48-81).
Twenty-seven patients had relapsed/refractory AML, 4 had relapsed/refractory MDS, 2 had untreated AML, 1 had CMML, and 1 had granulocytic sarcoma. Thirty-one patients had R140Q IDH2 mutations, and 4 had R172K IDH2 mutations.
The patients received AG-221 at doses ranging from 30 mg BID to 150 mg QD. Patients completed a median of 1 cycle of treatment (range, <1-5+) and a mean of 2 cycles.
The drug was generally well-tolerated, largely prompting grade 1 or 2 adverse events. Grade 3 or higher events included thrombocytopenia (n=3), anemia (n=1), febrile neutropenia (n=3), sepsis (n=3), diarrhea (n=1), fatigue (n=1), leukocytosis (n=2), neutropenia (n=1), and rash (n=1).
Four patients had serious events possibly related to treatment. One patient had grade 3 confusion and grade 5 respiratory failure. One patient had grade 3 leukocytosis, grade 3 anorexia, and grade 1 nausea. One patient had grade 3 diarrhea. And 1 patient had grade 3 leukocytosis.
Twenty-five patients were evaluable for response. There were 6 complete responses (CRs), 2 CRs with incomplete platelet recovery, 1 CR with incomplete hematologic recovery, and 5 partial responses. Five patients had stable disease, and 6 had progressive disease.
The most responses occurred among patients who received AG-221 at 50 mg BID, and most responses occurred in cycle 1.
Twelve of the 14 responses are ongoing. Of the 8 patients who achieved a CR or CR with incomplete platelet recovery, 5 have lasted more than 2.5 months (range, 1-4+ months). And the 5 patients with stable disease remain on study.
This study is sponsored by Agios Pharmaceuticals Inc., the company developing AG-221 in collaboration with Celgene.
ESA recalled due to particulates
Amgen is recalling lots of the erythropoiesis-stimulating agent Aranesp (darbepoetin alfa) that were distributed in several countries outside the US.
The recall applies to 9 lots of Aranesp 500 mcg prefilled syringes from non-US distributors, wholesalers, and hospital pharmacies.
A routine quality examination revealed cellulose and/or polyester particles in a small number of syringes, so Amgen is recalling the 9 lots as a precautionary measure.
To date, there have been no complaints or adverse events that can be attributed to the presence of these particles.
The presence of particulate matter could elicit inflammatory and allergic responses, both chronic and acute, and may be life-threatening.
However, health implications may vary depending on the route of drug administration, the amount of particulate matter injected into the patient, the size of the particles, the patient’s underlying medical condition, and the presence of a right-to-left cardiac shunt.
The products impacted by the recall are Aranesp 500 mcg prefilled syringes. A single lot of Aranesp was packaged for different countries into 9 lots: 1042847, 1044141A, 1044141C, 1044141D, 1046891A, 1046891B, 1047394A, 1047622A, and 1047996A.
The impacted syringes were distributed in Belgium, Denmark, Finland, France, Ireland, Italy, Kuwait, Luxemburg, Russia, Saudi Arabia, Slovenia, Sweden, Switzerland, and the UK.
Consumers in the US who have questions regarding this recall can contact Amgen at 1-800-77-AMGEN (open 24 hours per day, 7 days per week).
Adverse events or quality problems associated with Aranesp can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
In the US, Aranesp is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis, or in patients with non-myeloid malignancies where anemia results from concomitantly administered chemotherapy.
Amgen is recalling lots of the erythropoiesis-stimulating agent Aranesp (darbepoetin alfa) that were distributed in several countries outside the US.
The recall applies to 9 lots of Aranesp 500 mcg prefilled syringes from non-US distributors, wholesalers, and hospital pharmacies.
A routine quality examination revealed cellulose and/or polyester particles in a small number of syringes, so Amgen is recalling the 9 lots as a precautionary measure.
To date, there have been no complaints or adverse events that can be attributed to the presence of these particles.
The presence of particulate matter could elicit inflammatory and allergic responses, both chronic and acute, and may be life-threatening.
However, health implications may vary depending on the route of drug administration, the amount of particulate matter injected into the patient, the size of the particles, the patient’s underlying medical condition, and the presence of a right-to-left cardiac shunt.
The products impacted by the recall are Aranesp 500 mcg prefilled syringes. A single lot of Aranesp was packaged for different countries into 9 lots: 1042847, 1044141A, 1044141C, 1044141D, 1046891A, 1046891B, 1047394A, 1047622A, and 1047996A.
The impacted syringes were distributed in Belgium, Denmark, Finland, France, Ireland, Italy, Kuwait, Luxemburg, Russia, Saudi Arabia, Slovenia, Sweden, Switzerland, and the UK.
Consumers in the US who have questions regarding this recall can contact Amgen at 1-800-77-AMGEN (open 24 hours per day, 7 days per week).
Adverse events or quality problems associated with Aranesp can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
In the US, Aranesp is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis, or in patients with non-myeloid malignancies where anemia results from concomitantly administered chemotherapy.
Amgen is recalling lots of the erythropoiesis-stimulating agent Aranesp (darbepoetin alfa) that were distributed in several countries outside the US.
The recall applies to 9 lots of Aranesp 500 mcg prefilled syringes from non-US distributors, wholesalers, and hospital pharmacies.
A routine quality examination revealed cellulose and/or polyester particles in a small number of syringes, so Amgen is recalling the 9 lots as a precautionary measure.
To date, there have been no complaints or adverse events that can be attributed to the presence of these particles.
The presence of particulate matter could elicit inflammatory and allergic responses, both chronic and acute, and may be life-threatening.
However, health implications may vary depending on the route of drug administration, the amount of particulate matter injected into the patient, the size of the particles, the patient’s underlying medical condition, and the presence of a right-to-left cardiac shunt.
The products impacted by the recall are Aranesp 500 mcg prefilled syringes. A single lot of Aranesp was packaged for different countries into 9 lots: 1042847, 1044141A, 1044141C, 1044141D, 1046891A, 1046891B, 1047394A, 1047622A, and 1047996A.
The impacted syringes were distributed in Belgium, Denmark, Finland, France, Ireland, Italy, Kuwait, Luxemburg, Russia, Saudi Arabia, Slovenia, Sweden, Switzerland, and the UK.
Consumers in the US who have questions regarding this recall can contact Amgen at 1-800-77-AMGEN (open 24 hours per day, 7 days per week).
Adverse events or quality problems associated with Aranesp can be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
In the US, Aranesp is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis, or in patients with non-myeloid malignancies where anemia results from concomitantly administered chemotherapy.
HDAC inhibitor gets orphan status for DLBCL
The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).
The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.
Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).
The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.
“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.
He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.
Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.
Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.
The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).
The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.
Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).
The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.
“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.
He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.
Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.
Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.
The US Food and Drug Administration (FDA) has granted orphan designation for the histone deacetylase (HDAC) inhibitor mocetinostat to treat diffuse large B-cell lymphoma (DLBCL). The drug already had orphan designation as a treatment for myelodysplastic syndrome (MDS).
The FDA grants orphan status to support the development of drugs for underserved patient populations or rare disorders affecting fewer than 200,000 people in the US.
Orphan designation provides the drug’s developer, Mirati Therapeutics, Inc., with certain benefits, including market exclusivity upon regulatory approval, exemption of FDA application fees, and tax credits for qualified clinical trials.
Mocetinostat works by reversing aberrant acetylation resulting from mutations in histone acetyltransferases (HATs).
The drug is being developed as a single-agent treatment for patients with DLBCL or bladder cancer characterized by HAT mutations that Mirati believes are critical in the pathogenesis and progression of these cancers.
“We have identified genetic alterations in histone acetylation pathways (CREBBP and EP300) in approximately one-third of DLBCL and bladder tumors,” said Charles Baum, MD, PhD, president and CEO of Mirati.
He added that nonclinical tumor models with these mutations have proven responsive to mocetinostat, so Mirati predicts the HDAC inhibitor will halt tumor progression and reduce tumor burden in patients.
Mocetinostat is also under investigation in phase 2 studies in combination with azacitidine (Vidaza) as a treatment for intermediate- and high-risk MDS.
Mocetinostat previously demonstrated activity, as well as toxicity, in patients with Hodgkin lymphoma.
Antibiotic recalled due to presence of particulates
Cubist Pharmaceuticals, Inc. is recalling 9 lots of the antibiotic Cubicin (daptomycin for injection), following complaints of foreign particulate matter in reconstituted vials.
Particulate matter in an intravenous drug poses a risk of thromboembolism and pulmonary embolism.
Other risks include phlebitis, the mechanical blocking of the capillaries or arterioles, the activation of platelets, the generation of microthrombi, and the formation of granulomas.
To date, there have been no adverse events associated with complaints of particulate matter from the 9 lots of Cubicin being recalled.
Cubicin is an intravenous product indicated for the treatment of skin infections and certain blood stream infections. The drug was distributed throughout the US, so the recall is nationwide.
The recall includes the following lots of Cubicin 500 mg (NDC 67919-011-01, UPC 3 67919-011-01 6):
Lot # Expiration date Ship dates
CDC203 DEC 2015 9/2/13 through 9/24/13
CDC207 JAN 2016 9/16/13 through 10/15/13
CDC213 FEB 2016 10/1/13 through 10/7/13
CDC217 MAR 2016 12/2/13 through 12/11/13
CDC226 APR 2016 7/29/13 through 8/26/13
CDC234 MAY 2016 8/26/13 through 9/19/13
CDC235 MAY 2016 9/19/13 through 10/17/13
CDC243 JUL 2016 10/17/13 through 11/12/13
CDC246 JUL 2016 11/12/13 through 12/2/13
Cubist Pharmaceuticals is notifying customers of this recall by letter and phone. Customers with product from the recalled lots should quarantine the product and discontinue distribution.
To arrange for the return and replacement of product, call Cubist at (855) 534-8309 between the hours of 9 am and 7 pm EDT, Monday through Friday.
Healthcare professionals and pharmacists with medical questions regarding this recall can contact Cubist Medical Information at (877) 282-4786 between the hours of 8 am and 5:30 pm EDT, Monday through Friday.
Adverse events or quality problems associated with the use of this product can be reported to the Food and Drug Administration’s MedWatch Adverse Events Program.
Cubist Pharmaceuticals, Inc. is recalling 9 lots of the antibiotic Cubicin (daptomycin for injection), following complaints of foreign particulate matter in reconstituted vials.
Particulate matter in an intravenous drug poses a risk of thromboembolism and pulmonary embolism.
Other risks include phlebitis, the mechanical blocking of the capillaries or arterioles, the activation of platelets, the generation of microthrombi, and the formation of granulomas.
To date, there have been no adverse events associated with complaints of particulate matter from the 9 lots of Cubicin being recalled.
Cubicin is an intravenous product indicated for the treatment of skin infections and certain blood stream infections. The drug was distributed throughout the US, so the recall is nationwide.
The recall includes the following lots of Cubicin 500 mg (NDC 67919-011-01, UPC 3 67919-011-01 6):
Lot # Expiration date Ship dates
CDC203 DEC 2015 9/2/13 through 9/24/13
CDC207 JAN 2016 9/16/13 through 10/15/13
CDC213 FEB 2016 10/1/13 through 10/7/13
CDC217 MAR 2016 12/2/13 through 12/11/13
CDC226 APR 2016 7/29/13 through 8/26/13
CDC234 MAY 2016 8/26/13 through 9/19/13
CDC235 MAY 2016 9/19/13 through 10/17/13
CDC243 JUL 2016 10/17/13 through 11/12/13
CDC246 JUL 2016 11/12/13 through 12/2/13
Cubist Pharmaceuticals is notifying customers of this recall by letter and phone. Customers with product from the recalled lots should quarantine the product and discontinue distribution.
To arrange for the return and replacement of product, call Cubist at (855) 534-8309 between the hours of 9 am and 7 pm EDT, Monday through Friday.
Healthcare professionals and pharmacists with medical questions regarding this recall can contact Cubist Medical Information at (877) 282-4786 between the hours of 8 am and 5:30 pm EDT, Monday through Friday.
Adverse events or quality problems associated with the use of this product can be reported to the Food and Drug Administration’s MedWatch Adverse Events Program.
Cubist Pharmaceuticals, Inc. is recalling 9 lots of the antibiotic Cubicin (daptomycin for injection), following complaints of foreign particulate matter in reconstituted vials.
Particulate matter in an intravenous drug poses a risk of thromboembolism and pulmonary embolism.
Other risks include phlebitis, the mechanical blocking of the capillaries or arterioles, the activation of platelets, the generation of microthrombi, and the formation of granulomas.
To date, there have been no adverse events associated with complaints of particulate matter from the 9 lots of Cubicin being recalled.
Cubicin is an intravenous product indicated for the treatment of skin infections and certain blood stream infections. The drug was distributed throughout the US, so the recall is nationwide.
The recall includes the following lots of Cubicin 500 mg (NDC 67919-011-01, UPC 3 67919-011-01 6):
Lot # Expiration date Ship dates
CDC203 DEC 2015 9/2/13 through 9/24/13
CDC207 JAN 2016 9/16/13 through 10/15/13
CDC213 FEB 2016 10/1/13 through 10/7/13
CDC217 MAR 2016 12/2/13 through 12/11/13
CDC226 APR 2016 7/29/13 through 8/26/13
CDC234 MAY 2016 8/26/13 through 9/19/13
CDC235 MAY 2016 9/19/13 through 10/17/13
CDC243 JUL 2016 10/17/13 through 11/12/13
CDC246 JUL 2016 11/12/13 through 12/2/13
Cubist Pharmaceuticals is notifying customers of this recall by letter and phone. Customers with product from the recalled lots should quarantine the product and discontinue distribution.
To arrange for the return and replacement of product, call Cubist at (855) 534-8309 between the hours of 9 am and 7 pm EDT, Monday through Friday.
Healthcare professionals and pharmacists with medical questions regarding this recall can contact Cubist Medical Information at (877) 282-4786 between the hours of 8 am and 5:30 pm EDT, Monday through Friday.
Adverse events or quality problems associated with the use of this product can be reported to the Food and Drug Administration’s MedWatch Adverse Events Program.
FDA approves bortezomib retreatment in MM
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for the retreatment of adults with multiple myeloma (MM) who previously responded to bortezomib and relapsed at least 6 months after that treatment.
Bortezomib’s label has been updated to include dosing guidelines and safety and efficacy findings for single-agent bortezomib and bortezomib in combination with dexamethasone in patients previously treated with bortezomib.
Bortezomib retreatment may be started at the last dose the patient tolerated.
The FDA approved bortezomib retreatment based on results of the phase 2 RETRIEVE study and other supportive data.
The single-arm RETRIEVE trial included 130 MM patients aged 18 years and older who had previously responded to bortezomib-based therapy and relapsed at least 6 months after the treatment. The patients had received a median of 2 prior therapies (range, 1 to 7).
In this study, 94 of the patients received bortezomib in combination with dexamethasone.
One patient achieved complete response to treatment, and 49 achieved partial responses, for an overall response rate of 38.5%. The median duration of response was 6.5 months (range, 0.6 to 19.3 months).
The safety profile with bortezomib retreatment was consistent with the known safety profile of intravenous bortezomib in relapsed MM. Researchers did not observer cumulative toxicities upon retreatment.
The most common adverse event was thrombocytopenia, which occurred in 52% of patients. The incidence of grade 3 or higher thrombocytopenia was 24%.
Peripheral neuropathy was also common, occurring in 28% of patients. Grade 3 or higher peripheral neuropathy occurred in 6% of patients.
The rate of serious adverse events was 12.3%. The most commonly reported serious adverse events were thrombocytopenia (3.8%), diarrhea (2.3%), herpes zoster (1.5%), and pneumonia (1.5%). Adverse events leading to discontinuation occurred in 13% of patients.
Bortezomib is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of bortezomib in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world.
Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote bortezomib in Japan. Bortezomib is approved in more than 90 countries.
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for the retreatment of adults with multiple myeloma (MM) who previously responded to bortezomib and relapsed at least 6 months after that treatment.
Bortezomib’s label has been updated to include dosing guidelines and safety and efficacy findings for single-agent bortezomib and bortezomib in combination with dexamethasone in patients previously treated with bortezomib.
Bortezomib retreatment may be started at the last dose the patient tolerated.
The FDA approved bortezomib retreatment based on results of the phase 2 RETRIEVE study and other supportive data.
The single-arm RETRIEVE trial included 130 MM patients aged 18 years and older who had previously responded to bortezomib-based therapy and relapsed at least 6 months after the treatment. The patients had received a median of 2 prior therapies (range, 1 to 7).
In this study, 94 of the patients received bortezomib in combination with dexamethasone.
One patient achieved complete response to treatment, and 49 achieved partial responses, for an overall response rate of 38.5%. The median duration of response was 6.5 months (range, 0.6 to 19.3 months).
The safety profile with bortezomib retreatment was consistent with the known safety profile of intravenous bortezomib in relapsed MM. Researchers did not observer cumulative toxicities upon retreatment.
The most common adverse event was thrombocytopenia, which occurred in 52% of patients. The incidence of grade 3 or higher thrombocytopenia was 24%.
Peripheral neuropathy was also common, occurring in 28% of patients. Grade 3 or higher peripheral neuropathy occurred in 6% of patients.
The rate of serious adverse events was 12.3%. The most commonly reported serious adverse events were thrombocytopenia (3.8%), diarrhea (2.3%), herpes zoster (1.5%), and pneumonia (1.5%). Adverse events leading to discontinuation occurred in 13% of patients.
Bortezomib is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of bortezomib in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world.
Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote bortezomib in Japan. Bortezomib is approved in more than 90 countries.
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for the retreatment of adults with multiple myeloma (MM) who previously responded to bortezomib and relapsed at least 6 months after that treatment.
Bortezomib’s label has been updated to include dosing guidelines and safety and efficacy findings for single-agent bortezomib and bortezomib in combination with dexamethasone in patients previously treated with bortezomib.
Bortezomib retreatment may be started at the last dose the patient tolerated.
The FDA approved bortezomib retreatment based on results of the phase 2 RETRIEVE study and other supportive data.
The single-arm RETRIEVE trial included 130 MM patients aged 18 years and older who had previously responded to bortezomib-based therapy and relapsed at least 6 months after the treatment. The patients had received a median of 2 prior therapies (range, 1 to 7).
In this study, 94 of the patients received bortezomib in combination with dexamethasone.
One patient achieved complete response to treatment, and 49 achieved partial responses, for an overall response rate of 38.5%. The median duration of response was 6.5 months (range, 0.6 to 19.3 months).
The safety profile with bortezomib retreatment was consistent with the known safety profile of intravenous bortezomib in relapsed MM. Researchers did not observer cumulative toxicities upon retreatment.
The most common adverse event was thrombocytopenia, which occurred in 52% of patients. The incidence of grade 3 or higher thrombocytopenia was 24%.
Peripheral neuropathy was also common, occurring in 28% of patients. Grade 3 or higher peripheral neuropathy occurred in 6% of patients.
The rate of serious adverse events was 12.3%. The most commonly reported serious adverse events were thrombocytopenia (3.8%), diarrhea (2.3%), herpes zoster (1.5%), and pneumonia (1.5%). Adverse events leading to discontinuation occurred in 13% of patients.
Bortezomib is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of bortezomib in the US. Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world.
Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote bortezomib in Japan. Bortezomib is approved in more than 90 countries.