User login
EC approves first immunostimulatory antibody to treat MM
Photo courtesy of
Bristol-Myers Squibb
The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.
Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.
Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Phase 3 trial
The EC approved elotuzumab 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.
The 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.
Baseline patient demographics and disease characteristics were well balanced between treatment arms.
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.
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%).
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure. 
Photo courtesy of
Bristol-Myers Squibb
The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.
Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.
Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Phase 3 trial
The EC approved elotuzumab 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.
The 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.
Baseline patient demographics and disease characteristics were well balanced between treatment arms.
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.
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%).
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.
Photo courtesy of
Bristol-Myers Squibb
The European Commission (EC) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy.
Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein expressed on myeloma cells, natural killer (NK) cells, plasma cells, and specific immune cell subsets of differentiated cells in the hematopoietic lineage.
Elotuzumab has a dual mechanism of action. It directly activates the immune system through NK cells via the SLAMF7 pathway, and it targets SLAMF7 on myeloma cells, tagging them for NK-cell-mediated destruction via antibody-dependent cellular toxicity.
Elotuzumab is the first immunostimulatory antibody approved to treat MM in the European Union.
Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.
Phase 3 trial
The EC approved elotuzumab 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.
The 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.
Baseline patient demographics and disease characteristics were well balanced between treatment arms.
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.
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%).
Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.
Study reveals potential treatment avenue for DBA, MDS
The production of two components of hemoglobin may be out of sync in Diamond Blackfan anemia (DBA) and myelodysplastic syndromes (MDS), according to a new study.
Researchers found that, in samples from patients with DBA or MDS, ribosome dysfunction delayed globin production, while heme synthesis proceeded normally.
This disruption in heme-globin coordination led to a buildup of toxic heme that killed red blood cell (RBC) precursors.
However, treating patient samples with a compound that blocks heme synthesis increased RBC production in both DBA and MDS.
Zhantao Yang, MD, of the University of Washington in Seattle, and his colleagues reported these findings in Science Translational Medicine.
Both DBA and MDS have been linked to defects in ribosome assembly, which is critical to protein production, but how this leads to anemia remains unknown.
To find out, Dr Yang and his colleagues analyzed bone marrow cells from patients with DBA (n=3) or MDS with del(5q) (n=6).
The researchers found that globin translation proceeded slowly in these samples, but heme synthesis proceeded normally.
This resulted in insufficient globin, excess heme, and excess reactive oxygen species in early erythroid precursors and, ultimately, the death of colony-forming unit–erythroid/proerythroblast cells.
The cells that were able to rapidly export heme or slow its synthesis survived and matured into RBCs, but the other colony-forming unit–erythroid cells/early proerythroblasts died.
The researchers noted that it is not clear how excess heme induces cell death in RBC precursors, but they said it likely involves both ferroptosis and apoptosis.
Regardless of the mechanism of cell death, the team found that treating the patients’ cells with succinylacetone (10 mM), a compound that blocks heme synthesis, improved RBC production.
The treatment improved RBC production in DBA and del(5q) MDS marrow cultures by 68% to 95% (P=0.03 to 0.05). In comparison, RBC production in control marrow cultures decreased by 4% to 13%.
The researchers said their experiments revealed additional important findings. First, they found that erythroid differentiation in the marrow cultures “excellently” phenocopied erythroid differentiation in vivo. This suggests these cultures can serve as a reliable platform in preclinical studies.
Second, the team said the fact that epigenetic differences between RBC precursors can lead to their preferential death or survival has broad implications. And querying the cells that preferentially survive could provide important insights.
The production of two components of hemoglobin may be out of sync in Diamond Blackfan anemia (DBA) and myelodysplastic syndromes (MDS), according to a new study.
Researchers found that, in samples from patients with DBA or MDS, ribosome dysfunction delayed globin production, while heme synthesis proceeded normally.
This disruption in heme-globin coordination led to a buildup of toxic heme that killed red blood cell (RBC) precursors.
However, treating patient samples with a compound that blocks heme synthesis increased RBC production in both DBA and MDS.
Zhantao Yang, MD, of the University of Washington in Seattle, and his colleagues reported these findings in Science Translational Medicine.
Both DBA and MDS have been linked to defects in ribosome assembly, which is critical to protein production, but how this leads to anemia remains unknown.
To find out, Dr Yang and his colleagues analyzed bone marrow cells from patients with DBA (n=3) or MDS with del(5q) (n=6).
The researchers found that globin translation proceeded slowly in these samples, but heme synthesis proceeded normally.
This resulted in insufficient globin, excess heme, and excess reactive oxygen species in early erythroid precursors and, ultimately, the death of colony-forming unit–erythroid/proerythroblast cells.
The cells that were able to rapidly export heme or slow its synthesis survived and matured into RBCs, but the other colony-forming unit–erythroid cells/early proerythroblasts died.
The researchers noted that it is not clear how excess heme induces cell death in RBC precursors, but they said it likely involves both ferroptosis and apoptosis.
Regardless of the mechanism of cell death, the team found that treating the patients’ cells with succinylacetone (10 mM), a compound that blocks heme synthesis, improved RBC production.
The treatment improved RBC production in DBA and del(5q) MDS marrow cultures by 68% to 95% (P=0.03 to 0.05). In comparison, RBC production in control marrow cultures decreased by 4% to 13%.
The researchers said their experiments revealed additional important findings. First, they found that erythroid differentiation in the marrow cultures “excellently” phenocopied erythroid differentiation in vivo. This suggests these cultures can serve as a reliable platform in preclinical studies.
Second, the team said the fact that epigenetic differences between RBC precursors can lead to their preferential death or survival has broad implications. And querying the cells that preferentially survive could provide important insights.
The production of two components of hemoglobin may be out of sync in Diamond Blackfan anemia (DBA) and myelodysplastic syndromes (MDS), according to a new study.
Researchers found that, in samples from patients with DBA or MDS, ribosome dysfunction delayed globin production, while heme synthesis proceeded normally.
This disruption in heme-globin coordination led to a buildup of toxic heme that killed red blood cell (RBC) precursors.
However, treating patient samples with a compound that blocks heme synthesis increased RBC production in both DBA and MDS.
Zhantao Yang, MD, of the University of Washington in Seattle, and his colleagues reported these findings in Science Translational Medicine.
Both DBA and MDS have been linked to defects in ribosome assembly, which is critical to protein production, but how this leads to anemia remains unknown.
To find out, Dr Yang and his colleagues analyzed bone marrow cells from patients with DBA (n=3) or MDS with del(5q) (n=6).
The researchers found that globin translation proceeded slowly in these samples, but heme synthesis proceeded normally.
This resulted in insufficient globin, excess heme, and excess reactive oxygen species in early erythroid precursors and, ultimately, the death of colony-forming unit–erythroid/proerythroblast cells.
The cells that were able to rapidly export heme or slow its synthesis survived and matured into RBCs, but the other colony-forming unit–erythroid cells/early proerythroblasts died.
The researchers noted that it is not clear how excess heme induces cell death in RBC precursors, but they said it likely involves both ferroptosis and apoptosis.
Regardless of the mechanism of cell death, the team found that treating the patients’ cells with succinylacetone (10 mM), a compound that blocks heme synthesis, improved RBC production.
The treatment improved RBC production in DBA and del(5q) MDS marrow cultures by 68% to 95% (P=0.03 to 0.05). In comparison, RBC production in control marrow cultures decreased by 4% to 13%.
The researchers said their experiments revealed additional important findings. First, they found that erythroid differentiation in the marrow cultures “excellently” phenocopied erythroid differentiation in vivo. This suggests these cultures can serve as a reliable platform in preclinical studies.
Second, the team said the fact that epigenetic differences between RBC precursors can lead to their preferential death or survival has broad implications. And querying the cells that preferentially survive could provide important insights.
Long-term PPI use damages endothelial cells
Image courtesy of NIH
Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.
Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.
“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.
“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”
Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.
“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”
Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.
Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.
The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.
In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.
Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.
Image courtesy of NIH
Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.
Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.
“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.
“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”
Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.
“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”
Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.
Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.
The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.
In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.
Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.
Image courtesy of NIH
Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.
Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.
“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.
“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”
Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.
“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”
Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.
Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.
The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.
In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.
Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.
EC approves long-acting hemophilia B therapy
The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.
Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.
The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.
Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.
“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.
“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”
Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.
Phase 3 trial
The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,
followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.
Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.
The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.
Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.
“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.
“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”
Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.
Phase 3 trial
The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,
followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
The European Commission (EC) has approved albutrepenonacog alfa (Idelvion) to treat and prevent bleeding in children and adults with hemophilia B.
Albutrepenonacog alfa is a long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin.
The product is now approved for use as routine prophylaxis, for on-demand control of bleeding, and for the perioperative management of bleeding.
Appropriate patients age 12 and older can go up to 14 days between albutrepenonacog alfa infusions. This dosing interval has been achieved while maintaining high levels of factor IX activity—above 5% over 14 days at 75 IU/kg.
“Offering 14-day dosing, Idelvion helps patients maintain higher factor IX levels over a long period of time, providing them with greater freedom from frequent infusions,” said Elena Santagostino, MD, PhD, of the University of Milan/IRCCS Maggiore Hospital in Italy.
“This is an important attribute for my patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”
Albutrepenonacog alfa is being developed by CSL Behring. The company said the product will be launched in European markets in the coming months, as market access and pricing are obtained.
Phase 3 trial
The EC approved albutrepenonacog alfa based on results of the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks,
followed by a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
Silk keeps blood samples stable at high temps
Photo by Graham Colm
A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.
Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.
The team believes this technique could have broad applications for clinical care and research.
“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.
For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.
The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.
“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.
“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”
The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.
Photo by Graham Colm
A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.
Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.
The team believes this technique could have broad applications for clinical care and research.
“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.
For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.
The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.
“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.
“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”
The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.
Photo by Graham Colm
A new technique provides a way to keep blood samples stable for long periods at high temperatures, according to research published in PNAS.
Investigators found they could keep blood samples stable for nearly 3 months at temperatures as high as 113 degrees F by encapsulating them in air-dried silk protein.
The team believes this technique could have broad applications for clinical care and research.
“This approach should facilitate outpatient blood collection for disease screening and monitoring, particularly for underserved populations, and also serve needs of researchers and clinicians without access to centralized testing facilities,” said study author David L. Kaplan, PhD, of the Department of Biomedical Engineering at Tufts University in Medford, Massachusetts.
For this approach, Dr Kaplan and his colleagues mixed a solution or a powder of purified silk fibroin protein extracted from silkworm cocoons with blood or plasma and air-dried the mixture.
The air-dried silk films were stored at temperatures between 22 and 45 degrees C (71.6 to 113 degrees F). At set intervals, the researchers recovered the encapsulated blood samples by dissolving the films in water and analyzed them.
“We found that biomarkers could be successfully analyzed even after storage for 84 days at temperatures up to 113 degrees F,” said study author Jonathan A. Kluge, PhD, formerly of Tufts University but now at Vaxess Technologies in Cambridge, Massachusetts.
“Encapsulation of samples in silk provided better protection than the traditional approach of drying on paper, especially at these elevated temperatures, which a shipment might encounter during overseas or summer transport.”
The investigators noted that the silk-based technique requires accurate starting volumes of the blood or other specimens to be known, and salts or other buffers are needed to reconstitute samples for accurate testing of certain markers.
Change to EHR can increase use of generic drugs
Photo courtesy of NIH
Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.
The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.
To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”
The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.
“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”
For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.
Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.
When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.
The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).
The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).
The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.
The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.
“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.
“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”
Photo courtesy of NIH
Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.
The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.
To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”
The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.
“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”
For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.
Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.
When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.
The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).
The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).
The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.
The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.
“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.
“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”
Photo courtesy of NIH
Changing the default prescription settings in the electronic health record (EHR) can increase the prescribing rates of generic drugs, according to a study published in JAMA Internal Medicine.
The study showed an increase in generic prescribing rates from 75% to 98% when prescriptions were defaulted to a generic medication (if available) in the EHR.
To order the brand name drug, physicians had to opt out by checking a box labelled “dispense as written.”
The study, which builds upon previous research, indicates that the manner in which default options are designed and implemented can influence physician behavior.
“Many of the decisions physicians make are shifting from pen and paper to digital platforms, like the electronic health record, yet there lacks sufficient evidence on how to design choice architecture within these environments to improve healthcare value and outcomes,” said study author Mitesh S. Patel, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
“Our results demonstrate that default options are a powerful tool for influencing physician behaviors but that they have to be well-designed to achieve the intended goals.”
For the study, Dr Patel and his colleagues tracked prescribing rates of oral medications for 10 common medical conditions across the University of Pennsylvania Health System.
Rather than changing prescription default settings to display generic names instead of brand names—a change that previously resulted in a 5% change in prescribing habits—in the new study, an opt-out checkbox was used.
When a physician prescribed a drug for a patient, the EHR would default to an equivalent generic. However, the physician could still prescribe the brand name when warranted by selecting the “dispense as written” checkbox.
The researchers compared prescribing rates between the pre-intervention period (January 2014 to October 2014) and the post-intervention period (December 2014 to June 2015).
The results showed that, during the pre-intervention period, generic drugs were prescribed 75.3% of the time, compared to 98.4% of the time during the post-intervention period (P<0.001).
The researchers said this indicates that, for most drugs, physicians specified the brand name should be prescribed only 2% of the time.
The exception to the trend was when physicians prescribed Synthroid for patients with thyroid conditions, as this brand name drug is known to have different hormone levels than its generic version, levothyroxine. In this case, physicians opted out and selected the brand name 22% of the time.
“Studies examining these seemingly minute details point to the importance of design when implementing defaults, which is something that could in result in a significant savings for patients and health systems, and hasn’t previously been examined closely in a healthcare setting,” said study author C. William Hanson, MD, of the Perelman School of Medicine.
“If a simple, low-cost change like adding an opt-out check box to prescription settings can make such a significant impact, there are likely other refinements that can be made just as easily that will also result in cost savings for patients and health systems. It’s a valuable area of research to continue exploring.”
Study suggests ticagrelor comparable to aspirin
Photo courtesy of AstraZeneca
Results of the SOCRATES trial suggest that ticagrelor is about as safe and effective as aspirin for patients with acute ischemic stroke or transient ischemic attack.
The incidence of the study’s primary endpoint—a composite of stroke, myocardial infarction, and death at 90 days—was similar between the aspirin and ticagrelor arms.
Likewise, there was no significant difference between the arms with regard to safety endpoints.
These results were published in NEJM. The trial was funded by AstraZeneca, which markets ticagrelor as Brilinta.
SOCRATES was a double-blind, controlled trial that enrolled 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack. The patients had not received intravenous or intra-arterial thrombolysis and were not considered to have had a cardioembolic stroke.
Within 24 hours of symptom onset, the patients were randomized to receive ticagrelor (n=6589) or aspirin (n=6610).
Patients received ticagrelor at a loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2 through 90. Patients received aspirin at 300 mg on day 1, followed by 100 mg daily for days 2 through 90.
Overall, the differences in baseline characteristics between the treatment arms were not significant. The exceptions were the proportions of patients with a history of diabetes (higher in the ticagrelor arm) or hypertension (higher in the aspirin arm; P<0.05 for both).
The study’s primary endpoint was the occurrence of stroke, myocardial infarction, or death within 90 days. This endpoint occurred in 6.7% of patients in the ticagrelor arm and 7.5% of those in the aspirin arm. The hazard ratio (HR) was 0.89 (P=0.07).
One percent of patients in the ticagrelor arm died, as did 0.9% of patients in the aspirin arm (HR=1.18, P=0.36). The rates of myocardial infarction were 0.4% and 0.3%, respectively (HR=1.20, P=0.55).
The rates of all stroke were 5.9% and 6.8%, respectively (HR=0.86, P=0.03), and the rates of ischemic stroke were 5.8% and 6.7%, respectively (HR=0.87, P=0.046).
The researchers said the P values for all stroke and ischemic stroke were considered nonsignificant in accordance with the hierarchical testing plan used in this study.
Major bleeding occurred in 0.5% of patients in the ticagrelor arm and 0.6% of patients in the aspirin arm (HR=0.83, P=0.45).
Intracranial hemorrhage occurred in 0.2% and 0.3% of patients (HR=0.68, P=0.30), respectively. And fatal bleeding occurred in 0.1% of patients in both arms.
Photo courtesy of AstraZeneca
Results of the SOCRATES trial suggest that ticagrelor is about as safe and effective as aspirin for patients with acute ischemic stroke or transient ischemic attack.
The incidence of the study’s primary endpoint—a composite of stroke, myocardial infarction, and death at 90 days—was similar between the aspirin and ticagrelor arms.
Likewise, there was no significant difference between the arms with regard to safety endpoints.
These results were published in NEJM. The trial was funded by AstraZeneca, which markets ticagrelor as Brilinta.
SOCRATES was a double-blind, controlled trial that enrolled 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack. The patients had not received intravenous or intra-arterial thrombolysis and were not considered to have had a cardioembolic stroke.
Within 24 hours of symptom onset, the patients were randomized to receive ticagrelor (n=6589) or aspirin (n=6610).
Patients received ticagrelor at a loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2 through 90. Patients received aspirin at 300 mg on day 1, followed by 100 mg daily for days 2 through 90.
Overall, the differences in baseline characteristics between the treatment arms were not significant. The exceptions were the proportions of patients with a history of diabetes (higher in the ticagrelor arm) or hypertension (higher in the aspirin arm; P<0.05 for both).
The study’s primary endpoint was the occurrence of stroke, myocardial infarction, or death within 90 days. This endpoint occurred in 6.7% of patients in the ticagrelor arm and 7.5% of those in the aspirin arm. The hazard ratio (HR) was 0.89 (P=0.07).
One percent of patients in the ticagrelor arm died, as did 0.9% of patients in the aspirin arm (HR=1.18, P=0.36). The rates of myocardial infarction were 0.4% and 0.3%, respectively (HR=1.20, P=0.55).
The rates of all stroke were 5.9% and 6.8%, respectively (HR=0.86, P=0.03), and the rates of ischemic stroke were 5.8% and 6.7%, respectively (HR=0.87, P=0.046).
The researchers said the P values for all stroke and ischemic stroke were considered nonsignificant in accordance with the hierarchical testing plan used in this study.
Major bleeding occurred in 0.5% of patients in the ticagrelor arm and 0.6% of patients in the aspirin arm (HR=0.83, P=0.45).
Intracranial hemorrhage occurred in 0.2% and 0.3% of patients (HR=0.68, P=0.30), respectively. And fatal bleeding occurred in 0.1% of patients in both arms.
Photo courtesy of AstraZeneca
Results of the SOCRATES trial suggest that ticagrelor is about as safe and effective as aspirin for patients with acute ischemic stroke or transient ischemic attack.
The incidence of the study’s primary endpoint—a composite of stroke, myocardial infarction, and death at 90 days—was similar between the aspirin and ticagrelor arms.
Likewise, there was no significant difference between the arms with regard to safety endpoints.
These results were published in NEJM. The trial was funded by AstraZeneca, which markets ticagrelor as Brilinta.
SOCRATES was a double-blind, controlled trial that enrolled 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack. The patients had not received intravenous or intra-arterial thrombolysis and were not considered to have had a cardioembolic stroke.
Within 24 hours of symptom onset, the patients were randomized to receive ticagrelor (n=6589) or aspirin (n=6610).
Patients received ticagrelor at a loading dose of 180 mg on day 1, followed by 90 mg twice daily for days 2 through 90. Patients received aspirin at 300 mg on day 1, followed by 100 mg daily for days 2 through 90.
Overall, the differences in baseline characteristics between the treatment arms were not significant. The exceptions were the proportions of patients with a history of diabetes (higher in the ticagrelor arm) or hypertension (higher in the aspirin arm; P<0.05 for both).
The study’s primary endpoint was the occurrence of stroke, myocardial infarction, or death within 90 days. This endpoint occurred in 6.7% of patients in the ticagrelor arm and 7.5% of those in the aspirin arm. The hazard ratio (HR) was 0.89 (P=0.07).
One percent of patients in the ticagrelor arm died, as did 0.9% of patients in the aspirin arm (HR=1.18, P=0.36). The rates of myocardial infarction were 0.4% and 0.3%, respectively (HR=1.20, P=0.55).
The rates of all stroke were 5.9% and 6.8%, respectively (HR=0.86, P=0.03), and the rates of ischemic stroke were 5.8% and 6.7%, respectively (HR=0.87, P=0.046).
The researchers said the P values for all stroke and ischemic stroke were considered nonsignificant in accordance with the hierarchical testing plan used in this study.
Major bleeding occurred in 0.5% of patients in the ticagrelor arm and 0.6% of patients in the aspirin arm (HR=0.83, P=0.45).
Intracranial hemorrhage occurred in 0.2% and 0.3% of patients (HR=0.68, P=0.30), respectively. And fatal bleeding occurred in 0.1% of patients in both arms.
Vaccine can protect some adults from malaria long-term
Photo by James Gathany
An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.
Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.
Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.
Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.
In addition, the researchers said the vaccine was well-tolerated.
“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”
Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.
The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.
The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.
In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.
Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.
To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).
Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.
Safety
Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).
Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.
Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).
There were no serious adverse events attributed to vaccination.
Efficacy
The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.
The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×105 PfSPZ IV, compared to 73% with 4 doses of 2.7×105 PfSPZ IV.
The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×105 PfSPZ IV, compared to 55% with 4 doses of 2.7×105 PfSPZ IV.
In other words, after 4 immunizations with PfSPZ at 2.7×105 IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.
Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.
Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×105 to 2.7×106 PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.
Photo by James Gathany
An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.
Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.
Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.
Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.
In addition, the researchers said the vaccine was well-tolerated.
“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”
Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.
The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.
The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.
In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.
Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.
To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).
Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.
Safety
Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).
Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.
Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).
There were no serious adverse events attributed to vaccination.
Efficacy
The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.
The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×105 PfSPZ IV, compared to 73% with 4 doses of 2.7×105 PfSPZ IV.
The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×105 PfSPZ IV, compared to 55% with 4 doses of 2.7×105 PfSPZ IV.
In other words, after 4 immunizations with PfSPZ at 2.7×105 IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.
Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.
Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×105 to 2.7×106 PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.
Photo by James Gathany
An experimental vaccine can protect some healthy adults from malaria infection long-term, according to a phase 1 study.
Researchers tested the vaccine, PfSPZ, by exposing malaria-naïve adults to mosquitoes infected with the parasite Plasmodium falciparum.
Six of the 11 subjects who received PfSPZ at the optimal dose and schedule were free of malaria parasites after they were exposed to the mosquitoes at 21 weeks after immunization.
Five of these subjects were still free of malaria parasites after they were exposed to the mosquitoes at 59 weeks after immunization.
In addition, the researchers said the vaccine was well-tolerated.
“It is now clear that administering the PfSPZ vaccine intravenously confers long-term, sterile protection in a small number of subjects, which has not been achieved with other current vaccine approaches,” said Robert A. Seder, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
“Based on the favorable safety profile, we’re testing higher doses in larger trials to see if even greater protection can be achieved long-term against other P falciparum strains different than the vaccine strain.”
Dr Seder and his colleagues reported the results of the current trial in Nature Medicine.
The PfSPZ vaccine was developed and produced by Sanaria Inc., with support from several Small Business Innovation Research awards from the National Institute of Allergy and Infectious Diseases.
The PfSPZ vaccine is composed of live but weakened P falciparum sporozoites. Previous research showed the vaccine to be protective 3 weeks after immunization.
In this trial, researchers assessed if protection could last for 5 months to a year. The trial enrolled 101 healthy adults, ages 18 to 45, who had never had malaria.
Fifty-seven subjects were scheduled to receive the PfSPZ vaccine, and 32 were not vaccinated. Vaccine recipients were divided into several groups to assess the roles of the route of administration, dose, and number of immunizations in conferring short- and long-term protection against malaria.
To evaluate how well the PfSPZ vaccine prevented malaria infection, all subjects were exposed at varying times to the bites of mosquitoes carrying the same P falciparum strain from which the PfSPZ vaccine was derived—a process known as controlled human malaria infection (CHMI).
Fifty-five subjects completed all their scheduled vaccinations, and 52 of these subjects underwent at least 1 CHMI.
Safety
Seventy-two percent of the vaccinated subjects (n=41) did not have any solicited adverse events at the injection site after any vaccination. Twenty-six percent (n=15) had mild symptoms (pain and redness), and 1 patient (2%) had a moderate symptom (pain).
Fifty-six percent of vaccinated subjects (n=32) did not have solicited systemic adverse events.
Thirty-three percent (n=19) had mild systemic symptoms (malaise, myalgia, headache, chills, nausea, temperature, and joint pain), and 11% (n=6) had moderate systemic symptoms (malaise, myalgia, headache, chills, nausea, and joint pain).
There were no serious adverse events attributed to vaccination.
Efficacy
The researchers found the efficacy of the PfSPZ vaccine depended on the dose given, the number of vaccinations received, and the route of administration. A higher dose, a higher number of doses, and intravenous (IV) administration were all associated with increased efficacy.
The estimated vaccine efficacy against CHMI at 3 weeks after immunization was 24% with 3 doses of 2.7×105 PfSPZ IV, compared to 73% with 4 doses of 2.7×105 PfSPZ IV.
The estimated vaccine efficacy against CHMI at 21 weeks was 25% with 4 or 5 doses of 1.35×105 PfSPZ IV, compared to 55% with 4 doses of 2.7×105 PfSPZ IV.
In other words, after 4 immunizations with PfSPZ at 2.7×105 IV, 6 of 11 (55%) vaccinated subjects remained without parasitemia following CHMI at 21 weeks after immunization.
Five of the subjects without parasitemia underwent CHMI again at 59 weeks, and none developed parasitemia.
Based on these results, the researchers hypothesize that further increasing the dose of PfSPZ will increase the magnitude and durability of efficacy. They said ongoing studies using 4.5×105 to 2.7×106 PfSPZ per dose are assessing this for homologous CHMI, heterologous CHMI, and natural exposure in all age groups.
No gender-based differences in outcomes for TAVR patients
ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.
The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.
The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.
These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).
The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.
The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.
“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.
“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”
Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.
Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.
By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).
Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).
Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).
“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”
BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.
ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.
The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.
The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.
These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).
The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.
The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.
“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.
“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”
Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.
Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.
By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).
Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).
Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).
“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”
BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.
ORLANDO, FL—There are no significant gender-based differences in early outcomes for patients receiving anticoagulants after a transcatheter aortic valve replacement (TAVR), according to the BRAVO 3 trial.
The trial showed no difference between men and women with regard to major bleeding at 48 hours or vascular complications, major adverse cardiac events, and mortality at 30 days.
The results did reveal a trend toward improved survival for women who received bivalirudin as opposed to unfractionated heparin (UFH), but the difference was not significant.
These results were presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 Scientific Sessions (abstract available here).
The trial enrolled 802 patients who underwent contemporary TAVR procedures administered through the leg and received either bivalirudin or UFH.
The primary endpoint was major bleeding occurring within 48 hours. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3b, which is overt bleeding with a significant drop in hemoglobin or that requires surgical intervention and/or intravenous vasoactive agents to control.
“Prior evidence has shown that while women have a higher rate of survival post TAVR, they are at a greater risk of complications from bleeding soon after a procedure,” said study investigator Anita W. Asgar, MD, of the Montreal Heart Institute in Quebec, Canada.
“BRAVO 3 was designed to look at whether different anticoagulation medications could reduce the early risk in women.”
Of the 391 women in the study, 195 received bivalirudin and 196 received UFH. Of the 411 men, 209 received bivalirudin and 202 received UFH.
Women were older than men and had fewer comorbidities, such as coronary artery disease, atrial fibrillation, and diabetes. While women had a lower EuroSCORE I—a predictor of operative mortality in patients undergoing cardiac surgery—all patients were considered high-risk for TAVR.
By 48 hours, there was no significant difference between the sexes in major bleeding, which occurred in 8.2% of women and 7.8% of men (P=0.83).
Likewise, there was no significant difference in the incidence of death, myocardial infarction, stroke, and major bleeding combined at 30 days. The incidence was 16% in women and 15% in men (P=0.63).
Nineteen patients in each group were still alive at 30 days (P=0.87), 34 men and 29 women had a major adverse cardiac event (P=0.65), and 32 men and 43 women had vascular complications (P=0.12).
“The good news is that we found early outcomes for women were comparable to those of men,” Dr Asgar. “That being said, the BRAVO 3 study only looked at outcomes over 30 days, so the next step would be to see long-term results for post-TAVR procedures.”
BRAVO 3 did reveal a trend—although it was not statistically significant—that women who received bivalirudin had superior survival. Dr Asgar noted this indication could warrant further studies, with a larger population, on using bivalirudin over UFH for women.
Company warns of counterfeit drug
Photo by Bill Branson
Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.
The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.
However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.
BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.
Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.
Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.
Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.
Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.
Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.
Photo by Bill Branson
Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.
The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.
However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.
BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.
Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.
Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.
Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.
Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.
Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.
Photo by Bill Branson
Heritage Pharmaceuticals Inc., has announced the existence of a counterfeit drug product labeled as BiCNU® (carmustine for injection) 100 mg.
The company said that, to the best of its knowledge, the counterfeit product has only been distributed in India, Ireland, and Israel.
However, Heritage is consulting with the US Food and Drug Administration (FDA) to aid the agency’s evaluations of this product, assist with determining the source of the counterfeit drug, and prevent the further distribution of this product or its introduction into the US.
BiCNU® is primarily used for chemotherapy in the treatment of lymphomas, multiple myeloma, and brain cancers. But the drug is also used for immunosuppression before organ transplant or hematopoietic stem cell transplant.
Heritage said it has directly notified all customers and provided detailed information that will help them identify a counterfeit BiCNU® product. Customers have been instructed to examine their inventory immediately and to quarantine, discontinue distribution of, and return any suspected counterfeit product.
Any customers who may have recently distributed the BiCNU® products to their own customers have been asked to convey this information to their customers so they will be able to carefully examine all BiCNU® products before use and identify the characteristics of a suspected counterfeit product.
Any end users who believe they may have received a counterfeit drug should return the product to the pharmacy that dispensed the medicine.
Any US health practitioners who determine they are in possession of a counterfeit product should contact the FDA through MedWatch. Instructions for such reporting are available on the FDA website.
Anyone with questions about the counterfeit product should contact the Heritage customer call center directly at (866) 901-3784, which is open Monday through Friday, from 9 am to 5 pm EST.