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Device monitors methotrexate levels faster
Credit: Juan D. Alfonso
A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.
Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.
It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.
“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.
“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”
With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.
In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.
In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.
The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.
“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”
Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.
“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.
“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.” 
Credit: Juan D. Alfonso
A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.
Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.
It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.
“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.
“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”
With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.
In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.
In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.
The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.
“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”
Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.
“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.
“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.”
Credit: Juan D. Alfonso
A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.
Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.
It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.
“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.
“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”
With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.
In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.
In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.
The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.
“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”
Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.
“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.
“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.”
Drug gets orphan status for PNH in US
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal
hemoglobinuria (PNH).
Roughly 2 months ago, the European Medicines Agency (EMA) did the same.
Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is
planning to move the drug into clinical trials in 2015.
If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.
“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.
Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.
About AMY-101 and PNH
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
Texts improve malaria treatment adherence
Credit: Ed Yourdon
Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.
“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.
“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”
Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.
The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.
Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.
Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.
The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.
“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”
“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”
Credit: Ed Yourdon
Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.
“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.
“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”
Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.
The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.
Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.
Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.
The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.
“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”
“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”
Credit: Ed Yourdon
Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.
“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.
“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”
Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.
The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.
Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.
Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.
The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.
“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”
“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”
Newer blood linked to fewer complications from heart surgery
Credit: University of Ottawa
Heart Institute
VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.
Patients who received newer blood had a lower rate of mortality, infection, and renal failure.
They were also less likely to require prolonged ventilation or re-exploration for bleeding.
Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.
The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.
Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.
Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.
After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).
In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).
After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).
“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”
Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.
Credit: University of Ottawa
Heart Institute
VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.
Patients who received newer blood had a lower rate of mortality, infection, and renal failure.
They were also less likely to require prolonged ventilation or re-exploration for bleeding.
Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.
The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.
Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.
Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.
After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).
In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).
After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).
“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”
Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.
Credit: University of Ottawa
Heart Institute
VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.
Patients who received newer blood had a lower rate of mortality, infection, and renal failure.
They were also less likely to require prolonged ventilation or re-exploration for bleeding.
Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.
The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.
Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.
Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.
After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).
In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).
After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).
“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”
Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.
Obese ALL patients more likely to have MRD after induction
Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.
To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.
The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.
“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.
“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”
The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.
Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”
About one-third of the patients were obese or overweight at the time of diagnosis.
MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.
The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.
Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.
“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.
Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.
Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.
To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.
The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.
“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.
“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”
The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.
Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”
About one-third of the patients were obese or overweight at the time of diagnosis.
MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.
The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.
Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.
“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.
Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.
Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.
To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.
The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.
“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.
“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”
The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.
Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”
About one-third of the patients were obese or overweight at the time of diagnosis.
MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.
The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.
Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.
“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.
Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.
Bacterium could help control malaria, dengue
Credit: CDC
A bacterium isolated from a mosquito’s gut could aid the fight against malaria and dengue, according to a study published in PLOS Pathogens.
With previous research, scientists isolated Csp_P, a member of the family of chromobacteria, from the gut of Aedes aegypti mosquitoes.
Now, the team has found that Csp_P can directly inhibit malaria and dengue pathogens in vitro and shorten the life span of the mosquitoes that transmit both diseases.
George Dimopoulos, PhD, of Johns Hopkins University in Baltimore, Maryland, and his colleagues examined Csp_P’s actions on both mosquitoes and pathogens, and the results suggest that Csp_P might help to fight malaria and dengue at different levels.
The researchers added Csp_P to sugar water fed to mosquitoes and found that the bacteria are able to quickly colonize the gut of the two most important mosquito disease vectors—Aedes aegypti and Anopheles gambiae.
Moreover, the presence of Csp_P in the gut reduced the susceptibility of the respective mosquitoes to infection with the malaria parasite Plasmodium falciparum or with dengue virus.
Even without gut colonization, exposure to Csp_P through food or breeding water shortened the lifespan of adult mosquitoes and mosquito larvae of both species.
When the researchers tested whether Csp_P could act against the malaria or dengue pathogens directly, they found that the bacterium, likely through the production of toxic metabolites, can inhibit the growth of Plasmodium at various stages during the parasite’s life cycle and also abolish dengue virus infectivity.
The team said these toxic metabolites could potentially be developed into drugs to treat malaria and dengue.
Overall, the researchers concluded that Csp_P’s broad-spectrum antipathogen properties and ability to kill mosquitoes make it a good candidate for the development of novel control strategies for malaria and dengue, so it warrants further study.
Credit: CDC
A bacterium isolated from a mosquito’s gut could aid the fight against malaria and dengue, according to a study published in PLOS Pathogens.
With previous research, scientists isolated Csp_P, a member of the family of chromobacteria, from the gut of Aedes aegypti mosquitoes.
Now, the team has found that Csp_P can directly inhibit malaria and dengue pathogens in vitro and shorten the life span of the mosquitoes that transmit both diseases.
George Dimopoulos, PhD, of Johns Hopkins University in Baltimore, Maryland, and his colleagues examined Csp_P’s actions on both mosquitoes and pathogens, and the results suggest that Csp_P might help to fight malaria and dengue at different levels.
The researchers added Csp_P to sugar water fed to mosquitoes and found that the bacteria are able to quickly colonize the gut of the two most important mosquito disease vectors—Aedes aegypti and Anopheles gambiae.
Moreover, the presence of Csp_P in the gut reduced the susceptibility of the respective mosquitoes to infection with the malaria parasite Plasmodium falciparum or with dengue virus.
Even without gut colonization, exposure to Csp_P through food or breeding water shortened the lifespan of adult mosquitoes and mosquito larvae of both species.
When the researchers tested whether Csp_P could act against the malaria or dengue pathogens directly, they found that the bacterium, likely through the production of toxic metabolites, can inhibit the growth of Plasmodium at various stages during the parasite’s life cycle and also abolish dengue virus infectivity.
The team said these toxic metabolites could potentially be developed into drugs to treat malaria and dengue.
Overall, the researchers concluded that Csp_P’s broad-spectrum antipathogen properties and ability to kill mosquitoes make it a good candidate for the development of novel control strategies for malaria and dengue, so it warrants further study.
Credit: CDC
A bacterium isolated from a mosquito’s gut could aid the fight against malaria and dengue, according to a study published in PLOS Pathogens.
With previous research, scientists isolated Csp_P, a member of the family of chromobacteria, from the gut of Aedes aegypti mosquitoes.
Now, the team has found that Csp_P can directly inhibit malaria and dengue pathogens in vitro and shorten the life span of the mosquitoes that transmit both diseases.
George Dimopoulos, PhD, of Johns Hopkins University in Baltimore, Maryland, and his colleagues examined Csp_P’s actions on both mosquitoes and pathogens, and the results suggest that Csp_P might help to fight malaria and dengue at different levels.
The researchers added Csp_P to sugar water fed to mosquitoes and found that the bacteria are able to quickly colonize the gut of the two most important mosquito disease vectors—Aedes aegypti and Anopheles gambiae.
Moreover, the presence of Csp_P in the gut reduced the susceptibility of the respective mosquitoes to infection with the malaria parasite Plasmodium falciparum or with dengue virus.
Even without gut colonization, exposure to Csp_P through food or breeding water shortened the lifespan of adult mosquitoes and mosquito larvae of both species.
When the researchers tested whether Csp_P could act against the malaria or dengue pathogens directly, they found that the bacterium, likely through the production of toxic metabolites, can inhibit the growth of Plasmodium at various stages during the parasite’s life cycle and also abolish dengue virus infectivity.
The team said these toxic metabolites could potentially be developed into drugs to treat malaria and dengue.
Overall, the researchers concluded that Csp_P’s broad-spectrum antipathogen properties and ability to kill mosquitoes make it a good candidate for the development of novel control strategies for malaria and dengue, so it warrants further study.
Bortezomib can treat chronic GVHD, study shows
Credit: PLOS ONE
The proteasome inhibitor bortezomib can treat chronic graft-vs-host disease (GVHD), according to research published in Blood.
The study showed that bortezomib provides better outcomes than existing treatments and does not impair the graft-vs-tumor effect.
“Bortezomib helped a group of patients who desperately needed a treatment, having failed multiple different therapies,” said study author Mehrdad Abedi, MD, of the University of California, Davis.
“The drug fights chronic graft-vs-host disease, and, unlike other GVHD therapies such as steroid, cyclosporine, or mycophenolate, it treats chronic GVHD without dampening the graft-vs-tumor effect, which can be critically important to help patients avoid relapse. In fact, because bortezomib is an anticancer drug, it potentially attacks cancer cells in its own right.”
The researchers first studied bortezomib in mice and found the drug suppresses the donor immune cells that cause GVHD.
“We then tested this concept in patients with chronic GVHD . . . ,” Dr Abedi said. “Almost all the patients who tolerated and remained on the treatment responded. In some cases, individual responses were quite dramatic. We were able to stop their other immunosuppressive medications and keep the patients under control with just weekly injections of bortezomib.”
Dr Abedi added that one patient had severe hemolytic anemia that did not respond to several lines of therapy.
“After receiving bortezomib, the patient’s symptoms improved, and we were able to take her completely off steroid and other immunosuppressive medications,” he said. “Another person had multiple ulcers, which completely healed. These were patients who had been on all different kinds of medications and had no response.”
This research is ongoing. Dr Abedi and his colleagues are now looking at a potential oral version of the drug and a similar agent that would alleviate the need for weekly injections and could have fewer side effects.
This research was funded by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and Millennium Pharmaceuticals, makers of bortezomib.
Credit: PLOS ONE
The proteasome inhibitor bortezomib can treat chronic graft-vs-host disease (GVHD), according to research published in Blood.
The study showed that bortezomib provides better outcomes than existing treatments and does not impair the graft-vs-tumor effect.
“Bortezomib helped a group of patients who desperately needed a treatment, having failed multiple different therapies,” said study author Mehrdad Abedi, MD, of the University of California, Davis.
“The drug fights chronic graft-vs-host disease, and, unlike other GVHD therapies such as steroid, cyclosporine, or mycophenolate, it treats chronic GVHD without dampening the graft-vs-tumor effect, which can be critically important to help patients avoid relapse. In fact, because bortezomib is an anticancer drug, it potentially attacks cancer cells in its own right.”
The researchers first studied bortezomib in mice and found the drug suppresses the donor immune cells that cause GVHD.
“We then tested this concept in patients with chronic GVHD . . . ,” Dr Abedi said. “Almost all the patients who tolerated and remained on the treatment responded. In some cases, individual responses were quite dramatic. We were able to stop their other immunosuppressive medications and keep the patients under control with just weekly injections of bortezomib.”
Dr Abedi added that one patient had severe hemolytic anemia that did not respond to several lines of therapy.
“After receiving bortezomib, the patient’s symptoms improved, and we were able to take her completely off steroid and other immunosuppressive medications,” he said. “Another person had multiple ulcers, which completely healed. These were patients who had been on all different kinds of medications and had no response.”
This research is ongoing. Dr Abedi and his colleagues are now looking at a potential oral version of the drug and a similar agent that would alleviate the need for weekly injections and could have fewer side effects.
This research was funded by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and Millennium Pharmaceuticals, makers of bortezomib.
Credit: PLOS ONE
The proteasome inhibitor bortezomib can treat chronic graft-vs-host disease (GVHD), according to research published in Blood.
The study showed that bortezomib provides better outcomes than existing treatments and does not impair the graft-vs-tumor effect.
“Bortezomib helped a group of patients who desperately needed a treatment, having failed multiple different therapies,” said study author Mehrdad Abedi, MD, of the University of California, Davis.
“The drug fights chronic graft-vs-host disease, and, unlike other GVHD therapies such as steroid, cyclosporine, or mycophenolate, it treats chronic GVHD without dampening the graft-vs-tumor effect, which can be critically important to help patients avoid relapse. In fact, because bortezomib is an anticancer drug, it potentially attacks cancer cells in its own right.”
The researchers first studied bortezomib in mice and found the drug suppresses the donor immune cells that cause GVHD.
“We then tested this concept in patients with chronic GVHD . . . ,” Dr Abedi said. “Almost all the patients who tolerated and remained on the treatment responded. In some cases, individual responses were quite dramatic. We were able to stop their other immunosuppressive medications and keep the patients under control with just weekly injections of bortezomib.”
Dr Abedi added that one patient had severe hemolytic anemia that did not respond to several lines of therapy.
“After receiving bortezomib, the patient’s symptoms improved, and we were able to take her completely off steroid and other immunosuppressive medications,” he said. “Another person had multiple ulcers, which completely healed. These were patients who had been on all different kinds of medications and had no response.”
This research is ongoing. Dr Abedi and his colleagues are now looking at a potential oral version of the drug and a similar agent that would alleviate the need for weekly injections and could have fewer side effects.
This research was funded by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and Millennium Pharmaceuticals, makers of bortezomib.
Team creates functional vascular grafts in a week
Credit: Robert Emilsson
Researchers have found they can engineer vascular grafts using autologous peripheral blood and successfully transplant them into patients with portal vein thrombosis.
The team said this research provides early evidence for generating personalized blood vessels using stem cells from a blood sample rather than the bone marrow.
Suchitra Sumitran-Holgersson, PhD, of Sahlgrenska University Hospital in Sweden, and her colleagues described the work in EBioMedicine.
The researchers tested their new method on two young children with portal vein thrombosis.
The team used the patients’ own stem cells to grow new blood vessels, a procedure that had been performed at Sahlgrenska University Hospital once before. The novel finding was that they could do this without extracting the cells from the bone marrow.
The researchers took decellularized allogeneic vascular scaffolds and repopulated them with peripheral whole blood in a bioreactor.
The team found they could use 25 mL of blood, the minimum quantity needed to obtain enough stem cells. And the extraction procedure worked the first time.
“Not only that, but the blood itself accelerated growth of the new vein,” Dr Sumitran-Holgersson said. “The entire process took only a week, as opposed to a month in the first case. The blood contains substances that naturally promote growth.”
Dr Sumitran-Holgersson and her colleagues have treated three patients thus far. Two of those patients are still doing well and have veins that are functioning as they should. In the third case, the child is under medical surveillance, and the outcome is more uncertain.
“We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels,” Dr Sumitran-Holgersson said. “Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors.”
Credit: Robert Emilsson
Researchers have found they can engineer vascular grafts using autologous peripheral blood and successfully transplant them into patients with portal vein thrombosis.
The team said this research provides early evidence for generating personalized blood vessels using stem cells from a blood sample rather than the bone marrow.
Suchitra Sumitran-Holgersson, PhD, of Sahlgrenska University Hospital in Sweden, and her colleagues described the work in EBioMedicine.
The researchers tested their new method on two young children with portal vein thrombosis.
The team used the patients’ own stem cells to grow new blood vessels, a procedure that had been performed at Sahlgrenska University Hospital once before. The novel finding was that they could do this without extracting the cells from the bone marrow.
The researchers took decellularized allogeneic vascular scaffolds and repopulated them with peripheral whole blood in a bioreactor.
The team found they could use 25 mL of blood, the minimum quantity needed to obtain enough stem cells. And the extraction procedure worked the first time.
“Not only that, but the blood itself accelerated growth of the new vein,” Dr Sumitran-Holgersson said. “The entire process took only a week, as opposed to a month in the first case. The blood contains substances that naturally promote growth.”
Dr Sumitran-Holgersson and her colleagues have treated three patients thus far. Two of those patients are still doing well and have veins that are functioning as they should. In the third case, the child is under medical surveillance, and the outcome is more uncertain.
“We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels,” Dr Sumitran-Holgersson said. “Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors.”
Credit: Robert Emilsson
Researchers have found they can engineer vascular grafts using autologous peripheral blood and successfully transplant them into patients with portal vein thrombosis.
The team said this research provides early evidence for generating personalized blood vessels using stem cells from a blood sample rather than the bone marrow.
Suchitra Sumitran-Holgersson, PhD, of Sahlgrenska University Hospital in Sweden, and her colleagues described the work in EBioMedicine.
The researchers tested their new method on two young children with portal vein thrombosis.
The team used the patients’ own stem cells to grow new blood vessels, a procedure that had been performed at Sahlgrenska University Hospital once before. The novel finding was that they could do this without extracting the cells from the bone marrow.
The researchers took decellularized allogeneic vascular scaffolds and repopulated them with peripheral whole blood in a bioreactor.
The team found they could use 25 mL of blood, the minimum quantity needed to obtain enough stem cells. And the extraction procedure worked the first time.
“Not only that, but the blood itself accelerated growth of the new vein,” Dr Sumitran-Holgersson said. “The entire process took only a week, as opposed to a month in the first case. The blood contains substances that naturally promote growth.”
Dr Sumitran-Holgersson and her colleagues have treated three patients thus far. Two of those patients are still doing well and have veins that are functioning as they should. In the third case, the child is under medical surveillance, and the outcome is more uncertain.
“We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels,” Dr Sumitran-Holgersson said. “Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors.”
CHMP says ponatinib’s benefits outweigh risks
Credit: CDC
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted its final opinion on ponatinib (Iclusig), saying the drug’s benefits outweigh its risks.
The CHMP recommends that ponatinib continue to be used in accordance with its approved indications.
However, the drug’s product information should be updated with strengthened warnings, particularly about the risk of arterial and venous thrombotic events.
Ponatinib is approved in the European Union (EU) to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
Roughly a year ago, follow-up data revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Then, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events. The EMA also revised its recommendations for ponatinib but kept the drug on the market.
PRAC review and recommendations
Because of these risks, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) conducted an 11-month review of the available data on ponatinib and consulted with a scientific advisory group.
The PRAC assessed the available data on the nature, frequency, and severity of arterial and venous thrombotic events. And the committee concluded that the benefits of ponatinib outweigh its risks.
The PRAC said the risk of thrombotic events is likely dose-related, but there are insufficient data to formally recommend using lower doses of ponatinib. And there is a risk that lower doses might not be as effective in all patients and in long-term treatment.
The PRAC therefore concluded that the recommended starting dose of ponatinib should remain 45 mg once a day.
However, the committee also recommended updates to the product information to provide healthcare professionals with the latest evidence, in case they want to consider reducing the dose in patients with chronic phase CML who are responding well to treatment and who might be at particular risk of thrombotic events.
In addition, PRAC recommended that healthcare professionals stop ponatinib if there has been no response after 3 months of treatment and monitor patients for high blood pressure or signs of heart problems.
The CHMP concurred with these recommendations and is forwarding them to the European Commission. The commission is expected to issue a final, legally binding decision on ponatinib in December 2014, which will be valid throughout the EU.
A new study on the safety and benefits of ponatinib is in the works to help clarify if lower doses of the drug carry a lower risk of thrombotic events while still having a beneficial effect in patients with chronic phase CML.
Credit: CDC
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted its final opinion on ponatinib (Iclusig), saying the drug’s benefits outweigh its risks.
The CHMP recommends that ponatinib continue to be used in accordance with its approved indications.
However, the drug’s product information should be updated with strengthened warnings, particularly about the risk of arterial and venous thrombotic events.
Ponatinib is approved in the European Union (EU) to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
Roughly a year ago, follow-up data revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Then, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events. The EMA also revised its recommendations for ponatinib but kept the drug on the market.
PRAC review and recommendations
Because of these risks, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) conducted an 11-month review of the available data on ponatinib and consulted with a scientific advisory group.
The PRAC assessed the available data on the nature, frequency, and severity of arterial and venous thrombotic events. And the committee concluded that the benefits of ponatinib outweigh its risks.
The PRAC said the risk of thrombotic events is likely dose-related, but there are insufficient data to formally recommend using lower doses of ponatinib. And there is a risk that lower doses might not be as effective in all patients and in long-term treatment.
The PRAC therefore concluded that the recommended starting dose of ponatinib should remain 45 mg once a day.
However, the committee also recommended updates to the product information to provide healthcare professionals with the latest evidence, in case they want to consider reducing the dose in patients with chronic phase CML who are responding well to treatment and who might be at particular risk of thrombotic events.
In addition, PRAC recommended that healthcare professionals stop ponatinib if there has been no response after 3 months of treatment and monitor patients for high blood pressure or signs of heart problems.
The CHMP concurred with these recommendations and is forwarding them to the European Commission. The commission is expected to issue a final, legally binding decision on ponatinib in December 2014, which will be valid throughout the EU.
A new study on the safety and benefits of ponatinib is in the works to help clarify if lower doses of the drug carry a lower risk of thrombotic events while still having a beneficial effect in patients with chronic phase CML.
Credit: CDC
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted its final opinion on ponatinib (Iclusig), saying the drug’s benefits outweigh its risks.
The CHMP recommends that ponatinib continue to be used in accordance with its approved indications.
However, the drug’s product information should be updated with strengthened warnings, particularly about the risk of arterial and venous thrombotic events.
Ponatinib is approved in the European Union (EU) to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
Roughly a year ago, follow-up data revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Then, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events. The EMA also revised its recommendations for ponatinib but kept the drug on the market.
PRAC review and recommendations
Because of these risks, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) conducted an 11-month review of the available data on ponatinib and consulted with a scientific advisory group.
The PRAC assessed the available data on the nature, frequency, and severity of arterial and venous thrombotic events. And the committee concluded that the benefits of ponatinib outweigh its risks.
The PRAC said the risk of thrombotic events is likely dose-related, but there are insufficient data to formally recommend using lower doses of ponatinib. And there is a risk that lower doses might not be as effective in all patients and in long-term treatment.
The PRAC therefore concluded that the recommended starting dose of ponatinib should remain 45 mg once a day.
However, the committee also recommended updates to the product information to provide healthcare professionals with the latest evidence, in case they want to consider reducing the dose in patients with chronic phase CML who are responding well to treatment and who might be at particular risk of thrombotic events.
In addition, PRAC recommended that healthcare professionals stop ponatinib if there has been no response after 3 months of treatment and monitor patients for high blood pressure or signs of heart problems.
The CHMP concurred with these recommendations and is forwarding them to the European Commission. The commission is expected to issue a final, legally binding decision on ponatinib in December 2014, which will be valid throughout the EU.
A new study on the safety and benefits of ponatinib is in the works to help clarify if lower doses of the drug carry a lower risk of thrombotic events while still having a beneficial effect in patients with chronic phase CML.
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.