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FDA approves treatment for acquired hemophilia A
The US Food and Drug Administration (FDA) has approved a recombinant porcine factor VIII (FVIII) product known as Obizur to treat bleeding episodes in adults with acquired hemophilia A.
Obizur replaces the inhibited human FVIII with a recombinant porcine sequence FVIII based on the rationale that porcine FVIII is less susceptible to inactivation by circulating human FVIII antibodies.
Physicians can manage Obizur’s efficacy and safety by measuring FVIII activity levels.
The ability to measure FVIII levels gives physicians an objective marker of hemostasis that can guide dosing and prevent overdosing, said Rebecca Kruse-Jarres, MD, Director of the Hemophilia Care Program at Puget Sound Blood Center in Seattle and principal investigator of a phase 2/3 trial of Obizur.
Trial results
The FDA approved Obizur based on results of a prospective, multicenter, phase 2/3 trial in which adults with acquired hemophilia A received the product to treat serious bleeding episodes.
Twenty-nine patients were enrolled and evaluated for safety. Researchers determined that one of the patients did not actually have acquired hemophilia A, so this patient could not be evaluated for efficacy.
At 24 hours after the initial infusion, all 28 patients in the efficacy analysis had a positive response to Obizur. This meant that bleeding stopped or decreased, the patients experienced clinical stabilization or improvement, and FVIII levels were 20% or greater.
Eighty-six percent of patients (24/28) had successful treatment of their initial bleeding episode. The overall treatment success was determined by the investigator based on the ability to discontinue or reduce the dose and/or dosing frequency of Obizur.
The adverse reaction most frequently reported in the 29 patients in the safety analysis was the development of inhibitors to porcine FVIII.
Nineteen patients were negative for anti-porcine FVIII antibodies at baseline, and 5 of these patients (26%) developed anti-porcine FVIII antibodies following exposure to Obizur. Of the 10 patients with detectable anti-porcine FVIII antibodies at baseline, 2 (20%) experienced an increase in titer, and 8 (80%) decreased to a non-detectable titer.
About acquired hemophilia A and Obizur
Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder caused by the development of antibodies directed against the body’s own FVIII.
Acquired hemophilia A development has been related to other medical conditions or health states, such as pregnancy, cancer, or the use of certain medications. However, in about half of acquired hemophilia A cases, no underlying cause can be found.
Diagnosis of this condition can be difficult, and the severity of bleeding can make treatment challenging.
“The approval of [Obizur] provides an important therapeutic option for use in the care of patients with this rare disease,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The FDA previously granted Obizur orphan drug designation because it is intended for use in the treatment of a rare disease or condition. The product is manufactured by Baxter Healthcare Corporation.
Baxter said Obizur will be commercially available in the US in the coming months and is currently under regulatory review in Europe and Canada.
For more details on Obizur, see the full prescribing information. 
The US Food and Drug Administration (FDA) has approved a recombinant porcine factor VIII (FVIII) product known as Obizur to treat bleeding episodes in adults with acquired hemophilia A.
Obizur replaces the inhibited human FVIII with a recombinant porcine sequence FVIII based on the rationale that porcine FVIII is less susceptible to inactivation by circulating human FVIII antibodies.
Physicians can manage Obizur’s efficacy and safety by measuring FVIII activity levels.
The ability to measure FVIII levels gives physicians an objective marker of hemostasis that can guide dosing and prevent overdosing, said Rebecca Kruse-Jarres, MD, Director of the Hemophilia Care Program at Puget Sound Blood Center in Seattle and principal investigator of a phase 2/3 trial of Obizur.
Trial results
The FDA approved Obizur based on results of a prospective, multicenter, phase 2/3 trial in which adults with acquired hemophilia A received the product to treat serious bleeding episodes.
Twenty-nine patients were enrolled and evaluated for safety. Researchers determined that one of the patients did not actually have acquired hemophilia A, so this patient could not be evaluated for efficacy.
At 24 hours after the initial infusion, all 28 patients in the efficacy analysis had a positive response to Obizur. This meant that bleeding stopped or decreased, the patients experienced clinical stabilization or improvement, and FVIII levels were 20% or greater.
Eighty-six percent of patients (24/28) had successful treatment of their initial bleeding episode. The overall treatment success was determined by the investigator based on the ability to discontinue or reduce the dose and/or dosing frequency of Obizur.
The adverse reaction most frequently reported in the 29 patients in the safety analysis was the development of inhibitors to porcine FVIII.
Nineteen patients were negative for anti-porcine FVIII antibodies at baseline, and 5 of these patients (26%) developed anti-porcine FVIII antibodies following exposure to Obizur. Of the 10 patients with detectable anti-porcine FVIII antibodies at baseline, 2 (20%) experienced an increase in titer, and 8 (80%) decreased to a non-detectable titer.
About acquired hemophilia A and Obizur
Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder caused by the development of antibodies directed against the body’s own FVIII.
Acquired hemophilia A development has been related to other medical conditions or health states, such as pregnancy, cancer, or the use of certain medications. However, in about half of acquired hemophilia A cases, no underlying cause can be found.
Diagnosis of this condition can be difficult, and the severity of bleeding can make treatment challenging.
“The approval of [Obizur] provides an important therapeutic option for use in the care of patients with this rare disease,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The FDA previously granted Obizur orphan drug designation because it is intended for use in the treatment of a rare disease or condition. The product is manufactured by Baxter Healthcare Corporation.
Baxter said Obizur will be commercially available in the US in the coming months and is currently under regulatory review in Europe and Canada.
For more details on Obizur, see the full prescribing information.
The US Food and Drug Administration (FDA) has approved a recombinant porcine factor VIII (FVIII) product known as Obizur to treat bleeding episodes in adults with acquired hemophilia A.
Obizur replaces the inhibited human FVIII with a recombinant porcine sequence FVIII based on the rationale that porcine FVIII is less susceptible to inactivation by circulating human FVIII antibodies.
Physicians can manage Obizur’s efficacy and safety by measuring FVIII activity levels.
The ability to measure FVIII levels gives physicians an objective marker of hemostasis that can guide dosing and prevent overdosing, said Rebecca Kruse-Jarres, MD, Director of the Hemophilia Care Program at Puget Sound Blood Center in Seattle and principal investigator of a phase 2/3 trial of Obizur.
Trial results
The FDA approved Obizur based on results of a prospective, multicenter, phase 2/3 trial in which adults with acquired hemophilia A received the product to treat serious bleeding episodes.
Twenty-nine patients were enrolled and evaluated for safety. Researchers determined that one of the patients did not actually have acquired hemophilia A, so this patient could not be evaluated for efficacy.
At 24 hours after the initial infusion, all 28 patients in the efficacy analysis had a positive response to Obizur. This meant that bleeding stopped or decreased, the patients experienced clinical stabilization or improvement, and FVIII levels were 20% or greater.
Eighty-six percent of patients (24/28) had successful treatment of their initial bleeding episode. The overall treatment success was determined by the investigator based on the ability to discontinue or reduce the dose and/or dosing frequency of Obizur.
The adverse reaction most frequently reported in the 29 patients in the safety analysis was the development of inhibitors to porcine FVIII.
Nineteen patients were negative for anti-porcine FVIII antibodies at baseline, and 5 of these patients (26%) developed anti-porcine FVIII antibodies following exposure to Obizur. Of the 10 patients with detectable anti-porcine FVIII antibodies at baseline, 2 (20%) experienced an increase in titer, and 8 (80%) decreased to a non-detectable titer.
About acquired hemophilia A and Obizur
Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder caused by the development of antibodies directed against the body’s own FVIII.
Acquired hemophilia A development has been related to other medical conditions or health states, such as pregnancy, cancer, or the use of certain medications. However, in about half of acquired hemophilia A cases, no underlying cause can be found.
Diagnosis of this condition can be difficult, and the severity of bleeding can make treatment challenging.
“The approval of [Obizur] provides an important therapeutic option for use in the care of patients with this rare disease,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.
The FDA previously granted Obizur orphan drug designation because it is intended for use in the treatment of a rare disease or condition. The product is manufactured by Baxter Healthcare Corporation.
Baxter said Obizur will be commercially available in the US in the coming months and is currently under regulatory review in Europe and Canada.
For more details on Obizur, see the full prescribing information.
NICE supports use of rivaroxaban in ACS
Credit: Andre E.X. Brown
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending rivaroxaban (Xarelto) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).
The agency is recommending rivaroxaban in combination with aspirin plus clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the draft guidance.
Because rivaroxaban increases the risk of bleeding, NICE recommends that clinicians undertake a careful assessment of a patient’s bleeding risk prior to treatment and ensure patients understand the benefits and risks associated with rivaroxaban.
Furthermore, clinicians should reassess the relative benefits and risks of continuing rivaroxaban treatment no later than 12 months after starting treatment.
Clinical and cost-effectiveness
An independent appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
“The committee therefore recommended rivaroxaban as a cost-effective use of [National Health Service] resources,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
The committee noted that, according to Bayer Healthcare (makers of rivaroxaban), the base case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base case estimate was £5622 per QALY gained.
The committee acknowledged that there is uncertainty about the validity of the results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
The draft guidance for rivaroxaban in ACS can be found on the NICE website. The closing date for comments is November 13, 2014.
Credit: Andre E.X. Brown
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending rivaroxaban (Xarelto) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).
The agency is recommending rivaroxaban in combination with aspirin plus clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the draft guidance.
Because rivaroxaban increases the risk of bleeding, NICE recommends that clinicians undertake a careful assessment of a patient’s bleeding risk prior to treatment and ensure patients understand the benefits and risks associated with rivaroxaban.
Furthermore, clinicians should reassess the relative benefits and risks of continuing rivaroxaban treatment no later than 12 months after starting treatment.
Clinical and cost-effectiveness
An independent appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
“The committee therefore recommended rivaroxaban as a cost-effective use of [National Health Service] resources,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
The committee noted that, according to Bayer Healthcare (makers of rivaroxaban), the base case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base case estimate was £5622 per QALY gained.
The committee acknowledged that there is uncertainty about the validity of the results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
The draft guidance for rivaroxaban in ACS can be found on the NICE website. The closing date for comments is November 13, 2014.
Credit: Andre E.X. Brown
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending rivaroxaban (Xarelto) as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS).
The agency is recommending rivaroxaban in combination with aspirin plus clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the draft guidance.
Because rivaroxaban increases the risk of bleeding, NICE recommends that clinicians undertake a careful assessment of a patient’s bleeding risk prior to treatment and ensure patients understand the benefits and risks associated with rivaroxaban.
Furthermore, clinicians should reassess the relative benefits and risks of continuing rivaroxaban treatment no later than 12 months after starting treatment.
Clinical and cost-effectiveness
An independent appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
“The committee therefore recommended rivaroxaban as a cost-effective use of [National Health Service] resources,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
The committee noted that, according to Bayer Healthcare (makers of rivaroxaban), the base case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base case estimate was £5622 per QALY gained.
The committee acknowledged that there is uncertainty about the validity of the results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
The draft guidance for rivaroxaban in ACS can be found on the NICE website. The closing date for comments is November 13, 2014.
Supercomputers can predict drugs’ side effects
Credit: FDA
Scientists have found they can use supercomputers to identify proteins that cause adverse drug reactions.
The team noted that, during the drug development process, researchers often miss side effects that kill at least 100,000 patients a year.
In PLOS ONE, Montiago LaBute, PhD, of Lawrence Livermore National Laboratory in California, and his colleagues explained how we might use high-performance computers to solve this problem.
Side effects go undetected during drug development
A typical drug discovery process begins with identifying which proteins are associated with a specific disease. Candidate drug compounds are combined with target proteins to determine the drug’s efficacy and toxicity.
While this method allows researchers to identify side effects with many target proteins, there are myriad unknown, off-target proteins that may bind to the candidate drug and could cause unanticipated side effects.
Because it is cost-prohibitive to experimentally test a drug candidate against a potentially large set of proteins—and the list of possible off-targets is not known ahead of time—pharmaceutical companies usually only test a minimal set of off-target proteins during the early stages of drug discovery.
So certain adverse drug reactions remain undetected through the later stages of drug development, and the drugs may make it to the marketplace before these reactions are detected.
There have been several highly publicized medications with off-target protein side effects that have reached the marketplace. For example, Avandia, an anti-diabetic drug, caused heart attacks in some patients.
And Vioxx, an anti-inflammatory medication, caused heart attacks and strokes in certain patient populations. Both drugs were recalled because of their side effects.
“There were no indications of side effects of these medications in early testing or clinical trials,” Dr LaBute said. “We need a way to determine the safety of such therapeutics before they reach patients. Our work can help direct such drugs to patients who will benefit the most from them with the least amount of side effects.”
Supercomputers predict adverse drug reactions
Dr LaBute and colleagues tackled the problem by using supercomputers and information from public databases of drug compounds and proteins.
The databases included DrugBank, UniProt, and Protein Data Bank (PDB), as well as drug databases from the US Food and Drug Administration (FDA) and SIDER, which contain FDA-approved drugs with adverse drug reactions.
The team examined 4020 off-target proteins from DrugBank and UniProt. Those proteins were indexed against the PDB, which whittled the number down to 409 off-proteins that have high-quality 3D crystallographic X-ray diffraction structures essential for analysis in a computational setting.
The researchers fed the 409 off-target proteins into high-performance computer software known as VinaLC, along with 906 FDA-approved drug compounds. VinaLC used a molecular docking matrix that bound the drugs to the proteins. A score was given to each combination to assess whether effective binding occurred.
The team fed binding scores into another computer program and combined them with 560 FDA-approved drugs with known side effects. They used an algorithm to determine which proteins were associated with certain side effects.
In two categories of disorders—vascular disorders and neoplasms—the researchers’ computational model of predicting side effects was more predictive than current statistical methods that do not include binding scores.
In addition, the team’s calculations predicted new potential side effects. For example, they predicted a connection between a protein normally associated with cancer metastasis to vascular disorders like aneurysms.
“We have discovered a very viable way to find off-target proteins that are important for side effects,” Dr LaBute said. “This approach using [high-powered computers] and molecular docking to find [adverse drug reactions] never really existed before.”
The team’s findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to Dr LaBute. Now, his group’s goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.
“If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities,” Dr Labute said. “Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, healthcare providers, and the FDA to provide us with patient and therapeutic data.”
Credit: FDA
Scientists have found they can use supercomputers to identify proteins that cause adverse drug reactions.
The team noted that, during the drug development process, researchers often miss side effects that kill at least 100,000 patients a year.
In PLOS ONE, Montiago LaBute, PhD, of Lawrence Livermore National Laboratory in California, and his colleagues explained how we might use high-performance computers to solve this problem.
Side effects go undetected during drug development
A typical drug discovery process begins with identifying which proteins are associated with a specific disease. Candidate drug compounds are combined with target proteins to determine the drug’s efficacy and toxicity.
While this method allows researchers to identify side effects with many target proteins, there are myriad unknown, off-target proteins that may bind to the candidate drug and could cause unanticipated side effects.
Because it is cost-prohibitive to experimentally test a drug candidate against a potentially large set of proteins—and the list of possible off-targets is not known ahead of time—pharmaceutical companies usually only test a minimal set of off-target proteins during the early stages of drug discovery.
So certain adverse drug reactions remain undetected through the later stages of drug development, and the drugs may make it to the marketplace before these reactions are detected.
There have been several highly publicized medications with off-target protein side effects that have reached the marketplace. For example, Avandia, an anti-diabetic drug, caused heart attacks in some patients.
And Vioxx, an anti-inflammatory medication, caused heart attacks and strokes in certain patient populations. Both drugs were recalled because of their side effects.
“There were no indications of side effects of these medications in early testing or clinical trials,” Dr LaBute said. “We need a way to determine the safety of such therapeutics before they reach patients. Our work can help direct such drugs to patients who will benefit the most from them with the least amount of side effects.”
Supercomputers predict adverse drug reactions
Dr LaBute and colleagues tackled the problem by using supercomputers and information from public databases of drug compounds and proteins.
The databases included DrugBank, UniProt, and Protein Data Bank (PDB), as well as drug databases from the US Food and Drug Administration (FDA) and SIDER, which contain FDA-approved drugs with adverse drug reactions.
The team examined 4020 off-target proteins from DrugBank and UniProt. Those proteins were indexed against the PDB, which whittled the number down to 409 off-proteins that have high-quality 3D crystallographic X-ray diffraction structures essential for analysis in a computational setting.
The researchers fed the 409 off-target proteins into high-performance computer software known as VinaLC, along with 906 FDA-approved drug compounds. VinaLC used a molecular docking matrix that bound the drugs to the proteins. A score was given to each combination to assess whether effective binding occurred.
The team fed binding scores into another computer program and combined them with 560 FDA-approved drugs with known side effects. They used an algorithm to determine which proteins were associated with certain side effects.
In two categories of disorders—vascular disorders and neoplasms—the researchers’ computational model of predicting side effects was more predictive than current statistical methods that do not include binding scores.
In addition, the team’s calculations predicted new potential side effects. For example, they predicted a connection between a protein normally associated with cancer metastasis to vascular disorders like aneurysms.
“We have discovered a very viable way to find off-target proteins that are important for side effects,” Dr LaBute said. “This approach using [high-powered computers] and molecular docking to find [adverse drug reactions] never really existed before.”
The team’s findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to Dr LaBute. Now, his group’s goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.
“If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities,” Dr Labute said. “Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, healthcare providers, and the FDA to provide us with patient and therapeutic data.”
Credit: FDA
Scientists have found they can use supercomputers to identify proteins that cause adverse drug reactions.
The team noted that, during the drug development process, researchers often miss side effects that kill at least 100,000 patients a year.
In PLOS ONE, Montiago LaBute, PhD, of Lawrence Livermore National Laboratory in California, and his colleagues explained how we might use high-performance computers to solve this problem.
Side effects go undetected during drug development
A typical drug discovery process begins with identifying which proteins are associated with a specific disease. Candidate drug compounds are combined with target proteins to determine the drug’s efficacy and toxicity.
While this method allows researchers to identify side effects with many target proteins, there are myriad unknown, off-target proteins that may bind to the candidate drug and could cause unanticipated side effects.
Because it is cost-prohibitive to experimentally test a drug candidate against a potentially large set of proteins—and the list of possible off-targets is not known ahead of time—pharmaceutical companies usually only test a minimal set of off-target proteins during the early stages of drug discovery.
So certain adverse drug reactions remain undetected through the later stages of drug development, and the drugs may make it to the marketplace before these reactions are detected.
There have been several highly publicized medications with off-target protein side effects that have reached the marketplace. For example, Avandia, an anti-diabetic drug, caused heart attacks in some patients.
And Vioxx, an anti-inflammatory medication, caused heart attacks and strokes in certain patient populations. Both drugs were recalled because of their side effects.
“There were no indications of side effects of these medications in early testing or clinical trials,” Dr LaBute said. “We need a way to determine the safety of such therapeutics before they reach patients. Our work can help direct such drugs to patients who will benefit the most from them with the least amount of side effects.”
Supercomputers predict adverse drug reactions
Dr LaBute and colleagues tackled the problem by using supercomputers and information from public databases of drug compounds and proteins.
The databases included DrugBank, UniProt, and Protein Data Bank (PDB), as well as drug databases from the US Food and Drug Administration (FDA) and SIDER, which contain FDA-approved drugs with adverse drug reactions.
The team examined 4020 off-target proteins from DrugBank and UniProt. Those proteins were indexed against the PDB, which whittled the number down to 409 off-proteins that have high-quality 3D crystallographic X-ray diffraction structures essential for analysis in a computational setting.
The researchers fed the 409 off-target proteins into high-performance computer software known as VinaLC, along with 906 FDA-approved drug compounds. VinaLC used a molecular docking matrix that bound the drugs to the proteins. A score was given to each combination to assess whether effective binding occurred.
The team fed binding scores into another computer program and combined them with 560 FDA-approved drugs with known side effects. They used an algorithm to determine which proteins were associated with certain side effects.
In two categories of disorders—vascular disorders and neoplasms—the researchers’ computational model of predicting side effects was more predictive than current statistical methods that do not include binding scores.
In addition, the team’s calculations predicted new potential side effects. For example, they predicted a connection between a protein normally associated with cancer metastasis to vascular disorders like aneurysms.
“We have discovered a very viable way to find off-target proteins that are important for side effects,” Dr LaBute said. “This approach using [high-powered computers] and molecular docking to find [adverse drug reactions] never really existed before.”
The team’s findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to Dr LaBute. Now, his group’s goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.
“If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities,” Dr Labute said. “Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, healthcare providers, and the FDA to provide us with patient and therapeutic data.”
Ibrutinib gets EU approval for CLL, MCL
Credit: Steven Harbour
The European Commission has granted marketing approval for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) in the European Union (EU).
The drug is now approved to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), adults with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, and first-line CLL patients who have 17p deletion or TP53 mutation and are unsuitable for chemotherapy.
In the EU and all other countries except the US, ibrutinib is marketed by Janssen Pharmaceutical Companies. In the US, the drug is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The EU approval of ibrutinib was based on data from a phase 2 study (PCYC-1104) in patients with MCL, the phase 3 RESONATE trial (PCYC-1112-CA) in CLL and small lymphocytic lymphoma (SLL), and a phase 1b/2 study (PCYC-1102) in CLL/SLL.
PCYC-1104: Ibrutinib in MCL
Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.
The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.
The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.
Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).
Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.
RESONATE: Ibrutinib in CLL/SLL
Results of the RESONATE trial were reported at EHA 2014 and published in NEJM in July. This trial was stopped early after an interim analysis showed that ibrutinib-treated patients experienced a 78% reduction in the risk of disease progression or death.
The trial included 391 patients with relapsed or refractory CLL or SLL who were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.
The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).
Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).
Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39% of patients, respectively.
Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.
PCYC-1102: Ibrutinib in CLL/SLL
Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.
They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.
After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.
Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.
Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).
Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.
Credit: Steven Harbour
The European Commission has granted marketing approval for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) in the European Union (EU).
The drug is now approved to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), adults with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, and first-line CLL patients who have 17p deletion or TP53 mutation and are unsuitable for chemotherapy.
In the EU and all other countries except the US, ibrutinib is marketed by Janssen Pharmaceutical Companies. In the US, the drug is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The EU approval of ibrutinib was based on data from a phase 2 study (PCYC-1104) in patients with MCL, the phase 3 RESONATE trial (PCYC-1112-CA) in CLL and small lymphocytic lymphoma (SLL), and a phase 1b/2 study (PCYC-1102) in CLL/SLL.
PCYC-1104: Ibrutinib in MCL
Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.
The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.
The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.
Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).
Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.
RESONATE: Ibrutinib in CLL/SLL
Results of the RESONATE trial were reported at EHA 2014 and published in NEJM in July. This trial was stopped early after an interim analysis showed that ibrutinib-treated patients experienced a 78% reduction in the risk of disease progression or death.
The trial included 391 patients with relapsed or refractory CLL or SLL who were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.
The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).
Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).
Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39% of patients, respectively.
Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.
PCYC-1102: Ibrutinib in CLL/SLL
Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.
They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.
After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.
Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.
Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).
Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.
Credit: Steven Harbour
The European Commission has granted marketing approval for the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) in the European Union (EU).
The drug is now approved to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), adults with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, and first-line CLL patients who have 17p deletion or TP53 mutation and are unsuitable for chemotherapy.
In the EU and all other countries except the US, ibrutinib is marketed by Janssen Pharmaceutical Companies. In the US, the drug is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The EU approval of ibrutinib was based on data from a phase 2 study (PCYC-1104) in patients with MCL, the phase 3 RESONATE trial (PCYC-1112-CA) in CLL and small lymphocytic lymphoma (SLL), and a phase 1b/2 study (PCYC-1102) in CLL/SLL.
PCYC-1104: Ibrutinib in MCL
Results of this trial were presented at ASH 2012 and published in NEJM in 2013. The NEJM data included 111 patients who received ibrutinib at 560 mg daily in continuous, 28-day cycles until disease progression.
The overall response rate was 68%, with a complete response rate of 21% and a partial response rate of 47%. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months.
The estimated progression-free survival was 13.9 months, and the overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.
Common nonhematologic adverse events included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%), and decreased appetite (21%). The most common grade 3, 4, or 5 infection was pneumonia (6%).
Grade 3 and 4 hematologic adverse events included neutropenia (16%), thrombocytopenia (11%), and anemia (10%). Grade 3 bleeding events occurred in 5 patients.
RESONATE: Ibrutinib in CLL/SLL
Results of the RESONATE trial were reported at EHA 2014 and published in NEJM in July. This trial was stopped early after an interim analysis showed that ibrutinib-treated patients experienced a 78% reduction in the risk of disease progression or death.
The trial included 391 patients with relapsed or refractory CLL or SLL who were randomized to receive ibrutinib (n=195) or ofatumumab (n=196). Patients in the ofatumumab arm were allowed to cross over to ibrutinib if they progressed (n=57). The median time on study was 9.4 months.
The best overall response rate was higher in the ibrutinib arm than the ofatumumab arm, at 78% and 11%, respectively. And ibrutinib significantly prolonged progression-free survival. The median was 8.1 months in the ofatumumab arm and was not reached in the ibrutinib arm (P<0.0001).
Ibrutinib significantly prolonged overall survival as well. The median overall survival was not reached in either arm, but the hazard ratio was 0.434 (P=0.0049).
Adverse events occurred in 99% of patients in the ibrutinib arm and 98% of those in the ofatumumab arm. Grade 3/4 events occurred in 51% and 39% of patients, respectively.
Atrial fibrillation, bleeding-related events, diarrhea, and arthralgia were more common in the ibrutinib arm. Infusion-related reactions, peripheral sensory neuropathy, urticaria, night sweats, and pruritus were more common in the ofatumumab arm.
PCYC-1102: Ibrutinib in CLL/SLL
Results of this phase 1b/2 trial were published in The Lancet Oncology in January. The trial enrolled 29 patients with previously untreated CLL and 2 with SLL.
They received 28-day cycles of once-daily ibrutinib at 420 mg or 840 mg. The 840 mg dose was discontinued after enrollment had begun because the doses showed comparable activity.
After a median follow-up of 22.1 months, 71% of patients achieved an objective response. Four patients (13%) had a complete response. The median time to response was 1.9 months.
Study investigators did not establish whether ibrutinib confers improvements in survival or disease-related symptoms.
Common adverse events included diarrhea (68%), nausea (48%), fatigue (32%), peripheral edema (29%), hypertension (29%), dizziness (26%), dyspepsia (26%), upper respiratory tract infection (26%), arthralgia (23%), constipation (23%), urinary tract infection (23%), and vomiting (23%).
Grade 3 adverse events included diarrhea (13%), fatigue (3%), hypertension (6%), dizziness (3%), urinary tract infection (3%), headache (3%), back pain (3%), and neutropenia (3%). One patient (3%) had grade 4 thrombocytopenia.
NICE doesn’t support pomalidomide for MM
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
FDA approves drug for nausea, vomiting
The US Food and Drug Administration (FDA) has approved Akynzeo to treat nausea and vomiting in cancer patients undergoing chemotherapy. Akynzeo is a capsule consisting of two drugs, netupitant and palonosetron.
Palonosetron prevents nausea and vomiting in the acute phase—within the first 24 hours of chemotherapy initiation.
Netupitant prevents nausea and vomiting in the acute phase and the delayed phase—25 to 120 hours after chemotherapy began.
Akynzeo’s effectiveness was established in two clinical trials of 1720 cancer patients receiving chemotherapy. Patients were randomized to receive Akynzeo or oral palonosetron.
The trials were designed to measure whether the drugs prevented any vomiting episodes in the acute, delayed, and overall phases after the start of chemotherapy.
Most Akynzeo-treated patients did not experience any vomiting or require rescue medication for nausea during the acute (98.5%), delayed (90.4%), and overall phases (89.6%).
The same was true for patients who received palonosetron, although percentages were lower—89.7%, 80.1%, and 76.5%, respectively.
The second trial showed similar results.
Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation.
Akynzeo is distributed and marketed by Eisai Inc., under license from Helsinn Healthcare S.A.
The US Food and Drug Administration (FDA) has approved Akynzeo to treat nausea and vomiting in cancer patients undergoing chemotherapy. Akynzeo is a capsule consisting of two drugs, netupitant and palonosetron.
Palonosetron prevents nausea and vomiting in the acute phase—within the first 24 hours of chemotherapy initiation.
Netupitant prevents nausea and vomiting in the acute phase and the delayed phase—25 to 120 hours after chemotherapy began.
Akynzeo’s effectiveness was established in two clinical trials of 1720 cancer patients receiving chemotherapy. Patients were randomized to receive Akynzeo or oral palonosetron.
The trials were designed to measure whether the drugs prevented any vomiting episodes in the acute, delayed, and overall phases after the start of chemotherapy.
Most Akynzeo-treated patients did not experience any vomiting or require rescue medication for nausea during the acute (98.5%), delayed (90.4%), and overall phases (89.6%).
The same was true for patients who received palonosetron, although percentages were lower—89.7%, 80.1%, and 76.5%, respectively.
The second trial showed similar results.
Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation.
Akynzeo is distributed and marketed by Eisai Inc., under license from Helsinn Healthcare S.A.
The US Food and Drug Administration (FDA) has approved Akynzeo to treat nausea and vomiting in cancer patients undergoing chemotherapy. Akynzeo is a capsule consisting of two drugs, netupitant and palonosetron.
Palonosetron prevents nausea and vomiting in the acute phase—within the first 24 hours of chemotherapy initiation.
Netupitant prevents nausea and vomiting in the acute phase and the delayed phase—25 to 120 hours after chemotherapy began.
Akynzeo’s effectiveness was established in two clinical trials of 1720 cancer patients receiving chemotherapy. Patients were randomized to receive Akynzeo or oral palonosetron.
The trials were designed to measure whether the drugs prevented any vomiting episodes in the acute, delayed, and overall phases after the start of chemotherapy.
Most Akynzeo-treated patients did not experience any vomiting or require rescue medication for nausea during the acute (98.5%), delayed (90.4%), and overall phases (89.6%).
The same was true for patients who received palonosetron, although percentages were lower—89.7%, 80.1%, and 76.5%, respectively.
The second trial showed similar results.
Common side effects of Akynzeo in the clinical trials were headache, asthenia, fatigue, dyspepsia, and constipation.
Akynzeo is distributed and marketed by Eisai Inc., under license from Helsinn Healthcare S.A.
FDA approves drug for untreated MCL
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for use in previously untreated patients with mantle cell
lymphoma (MCL).
This is the first drug to be approved in the US for previously untreated patients with MCL.
The approval extends the utility of bortezomib beyond relapsed or refractory MCL, for which it has been approved since 2006.
The new approval is based on results of a phase 3 trial.
The study was a comparison of VcR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in 487 patients newly diagnosed with stage II, III, or IV MCL.
Survival and response
VcR-CAP demonstrated a 59% relative improvement in the study’s primary endpoint of progression-free survival. At a median follow-up of 40 months, the median progression-free survival was 25 months in the VcR-CAP arm and 14 months in the R-CHOP arm (hazard ratio [HR]=0.63, P<0.001).
However, there was no significant improvement in overall survival. The median overall survival was not reached in the VcR-CAP arm and was 56.3 months in the R-CHOP arm (HR=0.80; P=0.173).
Patients in the VcR-CAP arm had a higher rate of complete response/unconfirmed complete response than those in the R-CHOP arm—53% and 42%, respectively (P=0.007). But there was no significant difference in overall response—92% and 90%, respectively (P=0.275).
The time to progression was significantly longer in the VcR-CAP arm—30.5 months, compared to 16.1 months in the R-CHOP arm (HR=0.58; P<0.001). And the median time to subsequent treatment was significantly longer in the VcR-CAP arm—44.5 months vs 24.8 months (HR 0.50; P<0.001).
Adverse events
VcR-CAP was associated with additional but manageable toxicity compared to R-CHOP.
Serious adverse events were reported in 38% of patients in the VcR-CAP arm and 30% in the R-CHOP arm. Grade 3 or higher adverse events were reported in 93% and 85%, respectively.
There were similar rates of all-grade peripheral neuropathy between the VcR-CAP arm and the R-CHOP arm—30% and 29%, respectively. But the rate of grade 3 or higher peripheral neuropathy was significantly higher in the VcR-CAP arm—7.5% vs 4.1%.
The incidence of all-grade thrombocytopenia was substantially higher in the VcR-CAP arm than the R-CHOP arm—72% and 19%, respectively. But there was no significant difference in bleeding events—6% and 5%, respectively.
The incidence of all-grade neutropenia was 88% in the VcR-CAP arm and 74% in the R-CHOP arm. The rate of grade 3 or higher febrile neutropenia was 14% and 15%, respectively, and the rate of infection was 60% and 46%, respectively.
These data were presented at ASCO 2014 as abstract 8500.
Bortezomib is marketed as Velcade by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization in the US, and Janssen Pharmaceutical Companies are responsible for commercialization in the rest of the world.
For more details on the drug, visit www.velcade.com.
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for use in previously untreated patients with mantle cell
lymphoma (MCL).
This is the first drug to be approved in the US for previously untreated patients with MCL.
The approval extends the utility of bortezomib beyond relapsed or refractory MCL, for which it has been approved since 2006.
The new approval is based on results of a phase 3 trial.
The study was a comparison of VcR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in 487 patients newly diagnosed with stage II, III, or IV MCL.
Survival and response
VcR-CAP demonstrated a 59% relative improvement in the study’s primary endpoint of progression-free survival. At a median follow-up of 40 months, the median progression-free survival was 25 months in the VcR-CAP arm and 14 months in the R-CHOP arm (hazard ratio [HR]=0.63, P<0.001).
However, there was no significant improvement in overall survival. The median overall survival was not reached in the VcR-CAP arm and was 56.3 months in the R-CHOP arm (HR=0.80; P=0.173).
Patients in the VcR-CAP arm had a higher rate of complete response/unconfirmed complete response than those in the R-CHOP arm—53% and 42%, respectively (P=0.007). But there was no significant difference in overall response—92% and 90%, respectively (P=0.275).
The time to progression was significantly longer in the VcR-CAP arm—30.5 months, compared to 16.1 months in the R-CHOP arm (HR=0.58; P<0.001). And the median time to subsequent treatment was significantly longer in the VcR-CAP arm—44.5 months vs 24.8 months (HR 0.50; P<0.001).
Adverse events
VcR-CAP was associated with additional but manageable toxicity compared to R-CHOP.
Serious adverse events were reported in 38% of patients in the VcR-CAP arm and 30% in the R-CHOP arm. Grade 3 or higher adverse events were reported in 93% and 85%, respectively.
There were similar rates of all-grade peripheral neuropathy between the VcR-CAP arm and the R-CHOP arm—30% and 29%, respectively. But the rate of grade 3 or higher peripheral neuropathy was significantly higher in the VcR-CAP arm—7.5% vs 4.1%.
The incidence of all-grade thrombocytopenia was substantially higher in the VcR-CAP arm than the R-CHOP arm—72% and 19%, respectively. But there was no significant difference in bleeding events—6% and 5%, respectively.
The incidence of all-grade neutropenia was 88% in the VcR-CAP arm and 74% in the R-CHOP arm. The rate of grade 3 or higher febrile neutropenia was 14% and 15%, respectively, and the rate of infection was 60% and 46%, respectively.
These data were presented at ASCO 2014 as abstract 8500.
Bortezomib is marketed as Velcade by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization in the US, and Janssen Pharmaceutical Companies are responsible for commercialization in the rest of the world.
For more details on the drug, visit www.velcade.com.
The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for use in previously untreated patients with mantle cell
lymphoma (MCL).
This is the first drug to be approved in the US for previously untreated patients with MCL.
The approval extends the utility of bortezomib beyond relapsed or refractory MCL, for which it has been approved since 2006.
The new approval is based on results of a phase 3 trial.
The study was a comparison of VcR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in 487 patients newly diagnosed with stage II, III, or IV MCL.
Survival and response
VcR-CAP demonstrated a 59% relative improvement in the study’s primary endpoint of progression-free survival. At a median follow-up of 40 months, the median progression-free survival was 25 months in the VcR-CAP arm and 14 months in the R-CHOP arm (hazard ratio [HR]=0.63, P<0.001).
However, there was no significant improvement in overall survival. The median overall survival was not reached in the VcR-CAP arm and was 56.3 months in the R-CHOP arm (HR=0.80; P=0.173).
Patients in the VcR-CAP arm had a higher rate of complete response/unconfirmed complete response than those in the R-CHOP arm—53% and 42%, respectively (P=0.007). But there was no significant difference in overall response—92% and 90%, respectively (P=0.275).
The time to progression was significantly longer in the VcR-CAP arm—30.5 months, compared to 16.1 months in the R-CHOP arm (HR=0.58; P<0.001). And the median time to subsequent treatment was significantly longer in the VcR-CAP arm—44.5 months vs 24.8 months (HR 0.50; P<0.001).
Adverse events
VcR-CAP was associated with additional but manageable toxicity compared to R-CHOP.
Serious adverse events were reported in 38% of patients in the VcR-CAP arm and 30% in the R-CHOP arm. Grade 3 or higher adverse events were reported in 93% and 85%, respectively.
There were similar rates of all-grade peripheral neuropathy between the VcR-CAP arm and the R-CHOP arm—30% and 29%, respectively. But the rate of grade 3 or higher peripheral neuropathy was significantly higher in the VcR-CAP arm—7.5% vs 4.1%.
The incidence of all-grade thrombocytopenia was substantially higher in the VcR-CAP arm than the R-CHOP arm—72% and 19%, respectively. But there was no significant difference in bleeding events—6% and 5%, respectively.
The incidence of all-grade neutropenia was 88% in the VcR-CAP arm and 74% in the R-CHOP arm. The rate of grade 3 or higher febrile neutropenia was 14% and 15%, respectively, and the rate of infection was 60% and 46%, respectively.
These data were presented at ASCO 2014 as abstract 8500.
Bortezomib is marketed as Velcade by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization in the US, and Janssen Pharmaceutical Companies are responsible for commercialization in the rest of the world.
For more details on the drug, visit www.velcade.com.
Price increases drive spending on cancer drugs
Credit: Steven Harbour
The recent surge in spending on oral anticancer drugs in the US exceeds the increase in use of these drugs, new research shows.
Average quarterly national spending on oral oncologics increased 37% during the period studied, from $940 million in the first quarter of 2006 to $1.4 billion in the third quarter of 2011.
But the average quarterly use of these drugs in the same time period increased by only 10%.
This suggests price increases are a significant driver of spending trends.
Rena M. Conti, PhD, of the University of Chicago in Illinois, and her colleagues examined recent trends in spending and use of oral oncologics and disclosed their findings in Health Affairs.
Of the 47 drugs analyzed, most were targeted agents (30%), hormonal agents (26%), and alkylating agents (19%).
The researchers observed a significant increase in national spending on oral oncologics from 2006 to 2011—an estimated average quarterly increase of $20 million.
This was driven by brand-name, patent-protected drugs, but the use of these drugs climbed a comparatively small amount. Average quarterly spending of patent-protected drugs increased 61%, and average quarterly use increased 30% between 2006 and the period from September 2010 to September 2011.
“This is an exciting time, an era of breakthrough cancer drugs,” Dr Conti said. “Some of these medications have extended the lives of many people with certain types of cancer. However, spending on these brand-name oral oncologics is outstripping national spending on all pharmaceuticals and all medical care spending generally.”
The researchers also discovered that when oncologics lose patent protection, spending takes a nosedive. The use of newly off-patent drugs increased by 16%, but average quarterly spending on those drugs fell by 65%.
Another finding was that US spending on targeted anticancer agents increased from 35% of all oral cancer drugs in 2006 to nearly 60% in 2011.
Meanwhile, spending on hormonal agents decreased from 42% of total spending to 19%, spending on antimetabolites increased from 11% to 12%, and spending on alkylating agents decreased from 10% to 8%.
Credit: Steven Harbour
The recent surge in spending on oral anticancer drugs in the US exceeds the increase in use of these drugs, new research shows.
Average quarterly national spending on oral oncologics increased 37% during the period studied, from $940 million in the first quarter of 2006 to $1.4 billion in the third quarter of 2011.
But the average quarterly use of these drugs in the same time period increased by only 10%.
This suggests price increases are a significant driver of spending trends.
Rena M. Conti, PhD, of the University of Chicago in Illinois, and her colleagues examined recent trends in spending and use of oral oncologics and disclosed their findings in Health Affairs.
Of the 47 drugs analyzed, most were targeted agents (30%), hormonal agents (26%), and alkylating agents (19%).
The researchers observed a significant increase in national spending on oral oncologics from 2006 to 2011—an estimated average quarterly increase of $20 million.
This was driven by brand-name, patent-protected drugs, but the use of these drugs climbed a comparatively small amount. Average quarterly spending of patent-protected drugs increased 61%, and average quarterly use increased 30% between 2006 and the period from September 2010 to September 2011.
“This is an exciting time, an era of breakthrough cancer drugs,” Dr Conti said. “Some of these medications have extended the lives of many people with certain types of cancer. However, spending on these brand-name oral oncologics is outstripping national spending on all pharmaceuticals and all medical care spending generally.”
The researchers also discovered that when oncologics lose patent protection, spending takes a nosedive. The use of newly off-patent drugs increased by 16%, but average quarterly spending on those drugs fell by 65%.
Another finding was that US spending on targeted anticancer agents increased from 35% of all oral cancer drugs in 2006 to nearly 60% in 2011.
Meanwhile, spending on hormonal agents decreased from 42% of total spending to 19%, spending on antimetabolites increased from 11% to 12%, and spending on alkylating agents decreased from 10% to 8%.
Credit: Steven Harbour
The recent surge in spending on oral anticancer drugs in the US exceeds the increase in use of these drugs, new research shows.
Average quarterly national spending on oral oncologics increased 37% during the period studied, from $940 million in the first quarter of 2006 to $1.4 billion in the third quarter of 2011.
But the average quarterly use of these drugs in the same time period increased by only 10%.
This suggests price increases are a significant driver of spending trends.
Rena M. Conti, PhD, of the University of Chicago in Illinois, and her colleagues examined recent trends in spending and use of oral oncologics and disclosed their findings in Health Affairs.
Of the 47 drugs analyzed, most were targeted agents (30%), hormonal agents (26%), and alkylating agents (19%).
The researchers observed a significant increase in national spending on oral oncologics from 2006 to 2011—an estimated average quarterly increase of $20 million.
This was driven by brand-name, patent-protected drugs, but the use of these drugs climbed a comparatively small amount. Average quarterly spending of patent-protected drugs increased 61%, and average quarterly use increased 30% between 2006 and the period from September 2010 to September 2011.
“This is an exciting time, an era of breakthrough cancer drugs,” Dr Conti said. “Some of these medications have extended the lives of many people with certain types of cancer. However, spending on these brand-name oral oncologics is outstripping national spending on all pharmaceuticals and all medical care spending generally.”
The researchers also discovered that when oncologics lose patent protection, spending takes a nosedive. The use of newly off-patent drugs increased by 16%, but average quarterly spending on those drugs fell by 65%.
Another finding was that US spending on targeted anticancer agents increased from 35% of all oral cancer drugs in 2006 to nearly 60% in 2011.
Meanwhile, spending on hormonal agents decreased from 42% of total spending to 19%, spending on antimetabolites increased from 11% to 12%, and spending on alkylating agents decreased from 10% to 8%.
Program for poor can boost hospital profits
Credit: Petr Kratochvil
A federal program designed to help the poor may actually be used to help US hospitals increase their profits, according to research published in Health Affairs.
Researchers examined enrollment in the 340B program, which provides deep discounts on outpatient drug purchases.
They found that hospitals and clinics that joined the program since 2004 currently serve more affluent and well-insured communities than those that qualified for the program in previous years.
This supports the idea that the program is changing from one that serves patients in need to one that enriches hospitals and their affiliated clinics, according to the researchers.
“This study provides the first nationally representative empirical evidence suggesting that the program’s original intent is being eroded by the actions of certain hospitals,” said study author Rena M. Conti, PhD, of the University of Chicago in Illinois.
This study follows work by Dr Conti and Peter B. Bach, MD, of Memorial Sloan-Kettering Cancer Center in New York, that was published in JAMA last year.
The JAMA study explained how 340B-qualified hospital-affiliated clinics can boost profits thanks to discounts on expensive anticancer drugs. The facilities receive the discounts under the expectation that the savings will be passed on to poor patients.
“Hospitals qualify for the program based on the poverty of their inpatient census only,” Dr Conti said. “The affiliated clinics are the only 340B institutions not required to pass the discounts off to patients or their insurers, nor do they have to report to the government exactly how these profits are used to serve the poor. Insurers’ and their patients’ payments for outpatient drug treatment don’t reflect the discounts the hospital receives.”
The 340B program, which began in 1992, was designed to help selected hospitals and their outpatient clinics serve low-income and uninsured patients by providing discounts of 30% to 50% on outpatient drugs.
About a decade ago, enrollment in 340B began to increase rapidly. Now, more than a third of the 4375 US non-federal hospitals are 340B-qualified. Recent Congressional and news reports suggest that, for selected hospitals, profits off the 340B program can be significant.
For their new study, Drs Conti and Bach examined the populations served by hospitals and clinics qualifying for 340B before and after the decade-long growth spurt. They matched data for all hospitals and clinics registered with the 340B program to socioeconomic data from the US Census Bureau.
The results showed that communities served by hospital-affiliated clinics joining the program in 2004 or later tended to have higher household incomes, much less unemployment, and higher rates of health insurance.
The researchers said their findings are consistent with recent complaints that, rather than serving vulnerable communities, the 340B program is being used to increase profits for hospitals and their affiliated clinics.
Credit: Petr Kratochvil
A federal program designed to help the poor may actually be used to help US hospitals increase their profits, according to research published in Health Affairs.
Researchers examined enrollment in the 340B program, which provides deep discounts on outpatient drug purchases.
They found that hospitals and clinics that joined the program since 2004 currently serve more affluent and well-insured communities than those that qualified for the program in previous years.
This supports the idea that the program is changing from one that serves patients in need to one that enriches hospitals and their affiliated clinics, according to the researchers.
“This study provides the first nationally representative empirical evidence suggesting that the program’s original intent is being eroded by the actions of certain hospitals,” said study author Rena M. Conti, PhD, of the University of Chicago in Illinois.
This study follows work by Dr Conti and Peter B. Bach, MD, of Memorial Sloan-Kettering Cancer Center in New York, that was published in JAMA last year.
The JAMA study explained how 340B-qualified hospital-affiliated clinics can boost profits thanks to discounts on expensive anticancer drugs. The facilities receive the discounts under the expectation that the savings will be passed on to poor patients.
“Hospitals qualify for the program based on the poverty of their inpatient census only,” Dr Conti said. “The affiliated clinics are the only 340B institutions not required to pass the discounts off to patients or their insurers, nor do they have to report to the government exactly how these profits are used to serve the poor. Insurers’ and their patients’ payments for outpatient drug treatment don’t reflect the discounts the hospital receives.”
The 340B program, which began in 1992, was designed to help selected hospitals and their outpatient clinics serve low-income and uninsured patients by providing discounts of 30% to 50% on outpatient drugs.
About a decade ago, enrollment in 340B began to increase rapidly. Now, more than a third of the 4375 US non-federal hospitals are 340B-qualified. Recent Congressional and news reports suggest that, for selected hospitals, profits off the 340B program can be significant.
For their new study, Drs Conti and Bach examined the populations served by hospitals and clinics qualifying for 340B before and after the decade-long growth spurt. They matched data for all hospitals and clinics registered with the 340B program to socioeconomic data from the US Census Bureau.
The results showed that communities served by hospital-affiliated clinics joining the program in 2004 or later tended to have higher household incomes, much less unemployment, and higher rates of health insurance.
The researchers said their findings are consistent with recent complaints that, rather than serving vulnerable communities, the 340B program is being used to increase profits for hospitals and their affiliated clinics.
Credit: Petr Kratochvil
A federal program designed to help the poor may actually be used to help US hospitals increase their profits, according to research published in Health Affairs.
Researchers examined enrollment in the 340B program, which provides deep discounts on outpatient drug purchases.
They found that hospitals and clinics that joined the program since 2004 currently serve more affluent and well-insured communities than those that qualified for the program in previous years.
This supports the idea that the program is changing from one that serves patients in need to one that enriches hospitals and their affiliated clinics, according to the researchers.
“This study provides the first nationally representative empirical evidence suggesting that the program’s original intent is being eroded by the actions of certain hospitals,” said study author Rena M. Conti, PhD, of the University of Chicago in Illinois.
This study follows work by Dr Conti and Peter B. Bach, MD, of Memorial Sloan-Kettering Cancer Center in New York, that was published in JAMA last year.
The JAMA study explained how 340B-qualified hospital-affiliated clinics can boost profits thanks to discounts on expensive anticancer drugs. The facilities receive the discounts under the expectation that the savings will be passed on to poor patients.
“Hospitals qualify for the program based on the poverty of their inpatient census only,” Dr Conti said. “The affiliated clinics are the only 340B institutions not required to pass the discounts off to patients or their insurers, nor do they have to report to the government exactly how these profits are used to serve the poor. Insurers’ and their patients’ payments for outpatient drug treatment don’t reflect the discounts the hospital receives.”
The 340B program, which began in 1992, was designed to help selected hospitals and their outpatient clinics serve low-income and uninsured patients by providing discounts of 30% to 50% on outpatient drugs.
About a decade ago, enrollment in 340B began to increase rapidly. Now, more than a third of the 4375 US non-federal hospitals are 340B-qualified. Recent Congressional and news reports suggest that, for selected hospitals, profits off the 340B program can be significant.
For their new study, Drs Conti and Bach examined the populations served by hospitals and clinics qualifying for 340B before and after the decade-long growth spurt. They matched data for all hospitals and clinics registered with the 340B program to socioeconomic data from the US Census Bureau.
The results showed that communities served by hospital-affiliated clinics joining the program in 2004 or later tended to have higher household incomes, much less unemployment, and higher rates of health insurance.
The researchers said their findings are consistent with recent complaints that, rather than serving vulnerable communities, the 340B program is being used to increase profits for hospitals and their affiliated clinics.
Survey shows lack of adherence to safety guidelines
Credit: Bill Branson
Healthcare professionals do not consistently follow the recommended safe handling practices for antineoplastic drugs, according to a survey published in the Journal of Occupational and Environmental Hygiene.
Researchers surveyed more than 2000 healthcare workers and found that a majority do not always use the recommended personal protective equipment when they are administering antineoplastic drugs.
Furthermore, some respondents reported spills or leaks of a drug during administration, and a small percentage said they had experienced skin
contact with an antineoplastic drug.
“Chemotherapy drugs save lives of cancer patients but also can result in adverse health outcomes in workers who are exposed to these drugs, including cancer, reproductive problems, and organ damage when recommended safe handling guidelines are not followed,” said John Howard, MD, director of the National Institute for Occupational Safety and Health (NIOSH).
NIOSH researchers conducted this study, which included 2069 healthcare personnel who completed the 2011 Health and Safety Practices Survey of Healthcare Workers.
Results showed that, despite the longstanding availability of authoritative safe handling guidelines (ASHP, NIOSH, ONS, OSHA), recommended exposure controls were not always used.
For example, 80% of respondents said they do not always wear 2 pairs of chemotherapy gloves, and 15% said they don’t always wear a single pair.
Forty-two percent of respondents said they don’t always wear a nonabsorbent gown with a closed front and tight-fitting cuffs, and 12% had taken home potentially contaminated clothing.
Twelve percent of respondents reported a spill or leak of an antineoplastic drug during administration, and 4% reported skin contact with an antineoplastic drug.
Six percent of respondents said they primed intravenous tubing with an antineoplastic drug instead of a non-drug containing liquid, and 12% said the pharmacy department followed this practice.
Taking these and other findings into account, the researchers concluded that better risk communication is needed to ensure that employers and employees are fully aware of the hazards and the availability of precautionary measures to minimize exposure to antineoplastic drugs.
Credit: Bill Branson
Healthcare professionals do not consistently follow the recommended safe handling practices for antineoplastic drugs, according to a survey published in the Journal of Occupational and Environmental Hygiene.
Researchers surveyed more than 2000 healthcare workers and found that a majority do not always use the recommended personal protective equipment when they are administering antineoplastic drugs.
Furthermore, some respondents reported spills or leaks of a drug during administration, and a small percentage said they had experienced skin
contact with an antineoplastic drug.
“Chemotherapy drugs save lives of cancer patients but also can result in adverse health outcomes in workers who are exposed to these drugs, including cancer, reproductive problems, and organ damage when recommended safe handling guidelines are not followed,” said John Howard, MD, director of the National Institute for Occupational Safety and Health (NIOSH).
NIOSH researchers conducted this study, which included 2069 healthcare personnel who completed the 2011 Health and Safety Practices Survey of Healthcare Workers.
Results showed that, despite the longstanding availability of authoritative safe handling guidelines (ASHP, NIOSH, ONS, OSHA), recommended exposure controls were not always used.
For example, 80% of respondents said they do not always wear 2 pairs of chemotherapy gloves, and 15% said they don’t always wear a single pair.
Forty-two percent of respondents said they don’t always wear a nonabsorbent gown with a closed front and tight-fitting cuffs, and 12% had taken home potentially contaminated clothing.
Twelve percent of respondents reported a spill or leak of an antineoplastic drug during administration, and 4% reported skin contact with an antineoplastic drug.
Six percent of respondents said they primed intravenous tubing with an antineoplastic drug instead of a non-drug containing liquid, and 12% said the pharmacy department followed this practice.
Taking these and other findings into account, the researchers concluded that better risk communication is needed to ensure that employers and employees are fully aware of the hazards and the availability of precautionary measures to minimize exposure to antineoplastic drugs.
Credit: Bill Branson
Healthcare professionals do not consistently follow the recommended safe handling practices for antineoplastic drugs, according to a survey published in the Journal of Occupational and Environmental Hygiene.
Researchers surveyed more than 2000 healthcare workers and found that a majority do not always use the recommended personal protective equipment when they are administering antineoplastic drugs.
Furthermore, some respondents reported spills or leaks of a drug during administration, and a small percentage said they had experienced skin
contact with an antineoplastic drug.
“Chemotherapy drugs save lives of cancer patients but also can result in adverse health outcomes in workers who are exposed to these drugs, including cancer, reproductive problems, and organ damage when recommended safe handling guidelines are not followed,” said John Howard, MD, director of the National Institute for Occupational Safety and Health (NIOSH).
NIOSH researchers conducted this study, which included 2069 healthcare personnel who completed the 2011 Health and Safety Practices Survey of Healthcare Workers.
Results showed that, despite the longstanding availability of authoritative safe handling guidelines (ASHP, NIOSH, ONS, OSHA), recommended exposure controls were not always used.
For example, 80% of respondents said they do not always wear 2 pairs of chemotherapy gloves, and 15% said they don’t always wear a single pair.
Forty-two percent of respondents said they don’t always wear a nonabsorbent gown with a closed front and tight-fitting cuffs, and 12% had taken home potentially contaminated clothing.
Twelve percent of respondents reported a spill or leak of an antineoplastic drug during administration, and 4% reported skin contact with an antineoplastic drug.
Six percent of respondents said they primed intravenous tubing with an antineoplastic drug instead of a non-drug containing liquid, and 12% said the pharmacy department followed this practice.
Taking these and other findings into account, the researchers concluded that better risk communication is needed to ensure that employers and employees are fully aware of the hazards and the availability of precautionary measures to minimize exposure to antineoplastic drugs.