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Mixing warfarin, sulfonylurea may cause serious events
A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.
Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.
Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.
Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.
He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.
When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.
“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.
“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”
Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.
“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.
“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”
For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.
The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.
The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.
Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).
The researchers said these findings may not be generalizable beyond the elderly Medicare population.
They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly. 
A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.
Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.
Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.
Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.
He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.
When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.
“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.
“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”
Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.
“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.
“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”
For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.
The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.
The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.
Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).
The researchers said these findings may not be generalizable beyond the elderly Medicare population.
They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.
A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.
Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.
Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.
Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.
He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.
When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.
“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.
“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”
Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.
“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.
“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”
For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.
The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.
The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.
Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).
The researchers said these findings may not be generalizable beyond the elderly Medicare population.
They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.
FDA approves recombinant product for VWD
The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).
Vonvendi is the first FDA-approved recombinant von Willebrand factor.
It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.
Vonvendi is expected to be broadly available in the US in late 2016.
Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.
Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.
The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.
All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.
Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.
Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.
Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.
For more details on Vonvendi, see the product information.
The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).
Vonvendi is the first FDA-approved recombinant von Willebrand factor.
It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.
Vonvendi is expected to be broadly available in the US in late 2016.
Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.
Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.
The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.
All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.
Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.
Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.
Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.
For more details on Vonvendi, see the product information.
The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).
Vonvendi is the first FDA-approved recombinant von Willebrand factor.
It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.
Vonvendi is expected to be broadly available in the US in late 2016.
Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.
Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.
The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.
All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.
Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.
Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.
Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.
For more details on Vonvendi, see the product information.
Cancer drug prices vary widely from country to country
Photo by Bill Branson
The price of cancer drugs varies widely between European countries, Australia, and New Zealand, according to a study published in The Lancet Oncology.
The study indicates that, overall, the UK and Mediterranean countries such as Greece, Spain, and Portugal pay the lowest average unit manufacturer prices for a group of 31 originator cancer drugs (new drugs under patent).
And Sweden, Switzerland, and Germany pay the highest prices.
The greatest differences in price were noted for gemcitabine, which costs €209 per vial in New Zealand and €43 in Australia, and zoledronic acid, which costs €330 per vial in New Zealand but €128 in Greece.*
“Public payers in Germany are paying 223% more in terms of official prices for interferon alfa 2b for melanoma and leukemia treatment than those in Greece,” noted study author Sabine Vogler, PhD, of the WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies in Vienna, Austria.
“For gefitinib to treat non-small-lung cancer, the price in Germany is 172% higher than in New Zealand.”
To uncover these price differences, Dr Vogler and her colleagues reviewed official drug price data from the Pharma Price Information (PPI) service of the Austrian Public Health Institute for 16 European countries**, and from the pharmaceutical schedules in Australia and New Zealand.
The researchers compared what manufacturers charged for a unit (ie, price per tablet or vial) of 31 originator cancer drugs in June 2013.
None of these drugs had a unit price lower than €10. Four drugs (13%) had an average unit manufacturer price between €250 and €500, and 2 drugs (6%) had an average unit price between €500 and €1000.
Seven drugs (23%) had an average unit price higher than €1000. For example, plerixafor cost over €5000 per injection.
The price differences between the highest- and lowest-priced countries ranged from 28% to 50% for a third of the drugs sampled, between 50% and 100% for half of the drugs, and between 100% and 200% for 3 drugs (10%).
The researchers noted that information on real drug prices is scarce. The cancer drug prices they surveyed did not include confidential discounts such as those agreed upon in managed-entry arrangements that are increasingly used in countries such as Australia, Italy, the UK, and the Netherlands.
“Some high-income countries have managed to barter the manufacturers down to lower prices, but these agreements, including the agreed prices, are confidential,” Dr Vogler explained.
“Although these agreements ensure patient access to new drugs, other countries risk overpaying when setting drug prices through the common practice of external price referencing, or international price comparison, because they can only use the official undiscounted prices as a benchmark. There needs to be far more transparency.”
“We hope that our findings will provide concrete evidence for policymakers to take action to address high prices and ensure more transparency in cancer drug pricing so that costs and access to new drugs does not depend on where a patient lives.”
*Gemcitabine and zoledronic acid have generic versions in several countries, and originator prices were decreased in some countries following patent expiry but not in others.
**Austria, Belgium, Denmark, Germany, Greece, Finland, France, Italy, Ireland, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, and the UK.
Photo by Bill Branson
The price of cancer drugs varies widely between European countries, Australia, and New Zealand, according to a study published in The Lancet Oncology.
The study indicates that, overall, the UK and Mediterranean countries such as Greece, Spain, and Portugal pay the lowest average unit manufacturer prices for a group of 31 originator cancer drugs (new drugs under patent).
And Sweden, Switzerland, and Germany pay the highest prices.
The greatest differences in price were noted for gemcitabine, which costs €209 per vial in New Zealand and €43 in Australia, and zoledronic acid, which costs €330 per vial in New Zealand but €128 in Greece.*
“Public payers in Germany are paying 223% more in terms of official prices for interferon alfa 2b for melanoma and leukemia treatment than those in Greece,” noted study author Sabine Vogler, PhD, of the WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies in Vienna, Austria.
“For gefitinib to treat non-small-lung cancer, the price in Germany is 172% higher than in New Zealand.”
To uncover these price differences, Dr Vogler and her colleagues reviewed official drug price data from the Pharma Price Information (PPI) service of the Austrian Public Health Institute for 16 European countries**, and from the pharmaceutical schedules in Australia and New Zealand.
The researchers compared what manufacturers charged for a unit (ie, price per tablet or vial) of 31 originator cancer drugs in June 2013.
None of these drugs had a unit price lower than €10. Four drugs (13%) had an average unit manufacturer price between €250 and €500, and 2 drugs (6%) had an average unit price between €500 and €1000.
Seven drugs (23%) had an average unit price higher than €1000. For example, plerixafor cost over €5000 per injection.
The price differences between the highest- and lowest-priced countries ranged from 28% to 50% for a third of the drugs sampled, between 50% and 100% for half of the drugs, and between 100% and 200% for 3 drugs (10%).
The researchers noted that information on real drug prices is scarce. The cancer drug prices they surveyed did not include confidential discounts such as those agreed upon in managed-entry arrangements that are increasingly used in countries such as Australia, Italy, the UK, and the Netherlands.
“Some high-income countries have managed to barter the manufacturers down to lower prices, but these agreements, including the agreed prices, are confidential,” Dr Vogler explained.
“Although these agreements ensure patient access to new drugs, other countries risk overpaying when setting drug prices through the common practice of external price referencing, or international price comparison, because they can only use the official undiscounted prices as a benchmark. There needs to be far more transparency.”
“We hope that our findings will provide concrete evidence for policymakers to take action to address high prices and ensure more transparency in cancer drug pricing so that costs and access to new drugs does not depend on where a patient lives.”
*Gemcitabine and zoledronic acid have generic versions in several countries, and originator prices were decreased in some countries following patent expiry but not in others.
**Austria, Belgium, Denmark, Germany, Greece, Finland, France, Italy, Ireland, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, and the UK.
Photo by Bill Branson
The price of cancer drugs varies widely between European countries, Australia, and New Zealand, according to a study published in The Lancet Oncology.
The study indicates that, overall, the UK and Mediterranean countries such as Greece, Spain, and Portugal pay the lowest average unit manufacturer prices for a group of 31 originator cancer drugs (new drugs under patent).
And Sweden, Switzerland, and Germany pay the highest prices.
The greatest differences in price were noted for gemcitabine, which costs €209 per vial in New Zealand and €43 in Australia, and zoledronic acid, which costs €330 per vial in New Zealand but €128 in Greece.*
“Public payers in Germany are paying 223% more in terms of official prices for interferon alfa 2b for melanoma and leukemia treatment than those in Greece,” noted study author Sabine Vogler, PhD, of the WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies in Vienna, Austria.
“For gefitinib to treat non-small-lung cancer, the price in Germany is 172% higher than in New Zealand.”
To uncover these price differences, Dr Vogler and her colleagues reviewed official drug price data from the Pharma Price Information (PPI) service of the Austrian Public Health Institute for 16 European countries**, and from the pharmaceutical schedules in Australia and New Zealand.
The researchers compared what manufacturers charged for a unit (ie, price per tablet or vial) of 31 originator cancer drugs in June 2013.
None of these drugs had a unit price lower than €10. Four drugs (13%) had an average unit manufacturer price between €250 and €500, and 2 drugs (6%) had an average unit price between €500 and €1000.
Seven drugs (23%) had an average unit price higher than €1000. For example, plerixafor cost over €5000 per injection.
The price differences between the highest- and lowest-priced countries ranged from 28% to 50% for a third of the drugs sampled, between 50% and 100% for half of the drugs, and between 100% and 200% for 3 drugs (10%).
The researchers noted that information on real drug prices is scarce. The cancer drug prices they surveyed did not include confidential discounts such as those agreed upon in managed-entry arrangements that are increasingly used in countries such as Australia, Italy, the UK, and the Netherlands.
“Some high-income countries have managed to barter the manufacturers down to lower prices, but these agreements, including the agreed prices, are confidential,” Dr Vogler explained.
“Although these agreements ensure patient access to new drugs, other countries risk overpaying when setting drug prices through the common practice of external price referencing, or international price comparison, because they can only use the official undiscounted prices as a benchmark. There needs to be far more transparency.”
“We hope that our findings will provide concrete evidence for policymakers to take action to address high prices and ensure more transparency in cancer drug pricing so that costs and access to new drugs does not depend on where a patient lives.”
*Gemcitabine and zoledronic acid have generic versions in several countries, and originator prices were decreased in some countries following patent expiry but not in others.
**Austria, Belgium, Denmark, Germany, Greece, Finland, France, Italy, Ireland, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, and the UK.
FDA approves generic imatinib
Photo by Steven Harbour
The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.
Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.
The drug will be available in 100 mg and 400 mg tablets.
The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.
Sun Pharma’s imatinib mesylate is approved for the following indications:
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
- Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
- Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
- Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
- Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
- Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
- Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.
The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.
Photo by Steven Harbour
The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.
Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.
The drug will be available in 100 mg and 400 mg tablets.
The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.
Sun Pharma’s imatinib mesylate is approved for the following indications:
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
- Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
- Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
- Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
- Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
- Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
- Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.
The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.
Photo by Steven Harbour
The US Food and Drug Administration (FDA) has approved the use of imatinib mesylate, a generic version of Novartis’s Gleevec being developed by a subsidiary of Sun Pharmaceuticals Limited.
Under the terms of a settlement agreement with Novartis, the Sun Pharma subsidiary is allowed to launch its generic imatinib in the US on February 1, 2016.
The drug will be available in 100 mg and 400 mg tablets.
The Sun Pharma subsidiary was the first company to file an abbreviated new drug application for generic imatinib with a para IV certification and is therefore eligible for 180 days of marketing exclusivity in the US.
Sun Pharma’s imatinib mesylate is approved for the following indications:
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase
- Patients with (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
- Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia
- Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
- Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
- Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1- PDGFRα fusion kinase negative or unknown
- Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.
The drug is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.
FDA approves elotuzumab for MM
Photo courtesy of
Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.
Elotuzumab is the first immunostimulatory antibody approved for MM.
Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.
Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.
The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.
ELOQUENT-2 trial
The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.
The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.
Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.
The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.
The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).
The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).
The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).
Photo courtesy of
Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.
Elotuzumab is the first immunostimulatory antibody approved for MM.
Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.
Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.
The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.
ELOQUENT-2 trial
The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.
The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.
Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.
The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.
The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).
The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).
The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).
Photo courtesy of
Bristol-Myers Squibb
The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.
Elotuzumab is the first immunostimulatory antibody approved for MM.
Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.
Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.
The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.
ELOQUENT-2 trial
The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.
The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.
Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.
The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.
The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).
The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).
The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).
EC approves reversal agent for dabigatran
to prevent thrombosis after
knee replacement surgery
© Boehringer Ingelheim
The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.
The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.
Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.
The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.
Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:
- Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
- Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
- Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
to prevent thrombosis after
knee replacement surgery
© Boehringer Ingelheim
The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.
The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.
Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.
The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.
Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:
- Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
- Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
- Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
to prevent thrombosis after
knee replacement surgery
© Boehringer Ingelheim
The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.
The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.
Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.
The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.
Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:
- Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
- Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
- Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
EC grants conditional approval for blinatumomab
and solution for infusion
Photo courtesy of Amgen
The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).
This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
About blinatumomab
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.
BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.
Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.
The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.
Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
Blinatumomab is being developed by Amgen.
and solution for infusion
Photo courtesy of Amgen
The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).
This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
About blinatumomab
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.
BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.
Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.
The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.
Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
Blinatumomab is being developed by Amgen.
and solution for infusion
Photo courtesy of Amgen
The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).
This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
About blinatumomab
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.
BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.
Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.
The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.
Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
Blinatumomab is being developed by Amgen.
EC approves drug for hemophilia A
The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.
Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.
Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.
Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.
The product is expected to launch in initial EU countries in early 2016.
The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
About efmoroctocog alfa
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.
Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.
Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.
The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.
Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.
Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.
Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.
The product is expected to launch in initial EU countries in early 2016.
The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
About efmoroctocog alfa
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.
Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.
Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.
The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.
Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.
Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.
Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.
The product is expected to launch in initial EU countries in early 2016.
The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
About efmoroctocog alfa
Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.
Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.
Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.
Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.
Trial of ofatumumab in FL stopped early
Photo courtesy of GSK
Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.
The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.
An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.
Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.
“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”
The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m2) by intravenous infusion for 4 weekly doses.
Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.
Past disappointments
This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.
In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.
About ofatumumab
Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.
In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).
Photo courtesy of GSK
Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.
The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.
An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.
Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.
“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”
The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m2) by intravenous infusion for 4 weekly doses.
Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.
Past disappointments
This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.
In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.
About ofatumumab
Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.
In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).
Photo courtesy of GSK
Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.
The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.
An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.
Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.
“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”
The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m2) by intravenous infusion for 4 weekly doses.
Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.
Past disappointments
This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.
In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).
In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.
About ofatumumab
Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.
In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).
CHMP recommends pegaspargase for ALL
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.
If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.
These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase, see the product information.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.
If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.
These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase, see the product information.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.
If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.
These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase, see the product information.