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Health Canada expands indication for apixaban
Credit: Andre E.X. Brown
Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).
The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.
The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.
“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”
Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.
The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.
Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.
The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.
The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.
Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph. 
Credit: Andre E.X. Brown
Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).
The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.
The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.
“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”
Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.
The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.
Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.
The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.
The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.
Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph.
Credit: Andre E.X. Brown
Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).
The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.
The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.
“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”
Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.
The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.
Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.
The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.
The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.
Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph.
Studies reveal secrets of malaria transmission
Credit: James Gathany
Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.
There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.
Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.
Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.
The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.
In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.
A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.
Both groups described their work in Science Express.
The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.
Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.
“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.
The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.
“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”
The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.
The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.
Credit: James Gathany
Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.
There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.
Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.
Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.
The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.
In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.
A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.
Both groups described their work in Science Express.
The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.
Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.
“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.
The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.
“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”
The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.
The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.
Credit: James Gathany
Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.
There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.
Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.
Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.
The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.
In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.
A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.
Both groups described their work in Science Express.
The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.
Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.
“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.
The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.
“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”
The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.
The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.
Injectable hydrogel promotes coagulation
A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.
This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.
Once injected, the material locks into place at the site of the injury and decreases clotting time.
In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.
Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.
If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.
“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.
“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”
Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.
To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.
These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.
In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.
Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.
“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”
The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.
A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.
This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.
Once injected, the material locks into place at the site of the injury and decreases clotting time.
In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.
Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.
If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.
“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.
“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”
Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.
To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.
These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.
In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.
Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.
“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”
The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.
A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.
This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.
Once injected, the material locks into place at the site of the injury and decreases clotting time.
In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.
Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.
If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.
“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.
“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”
Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.
To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.
These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.
In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.
Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.
“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”
The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.
FDA influence on design of pivotal drug studies
Credit: FDA
New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.
When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.
Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.
The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.
These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.
To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.
The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.
Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.
Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.
Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.
Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.
Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.
Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.
The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.
An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.
Credit: FDA
New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.
When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.
Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.
The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.
These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.
To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.
The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.
Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.
Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.
Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.
Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.
Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.
Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.
The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.
An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.
Credit: FDA
New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.
When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.
Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.
The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.
These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.
To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.
The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.
Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.
Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.
Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.
Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.
Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.
Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.
The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.
An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.
Leukemia survival rates vary widely across the globe
Credit: Bill Branson
A large, international study has revealed sizable differences in cancer survival rates between countries.
In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).
The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.
This indicates major deficiencies in managing this largely curable disease, according to researchers.
Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.
Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.
The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.
The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.
Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.
Adult leukemia
For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.
Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.
ALL in children
For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.
However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.
The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.
Solid tumor malignancies
The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.
Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.
Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.
Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.
“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”
“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”
Credit: Bill Branson
A large, international study has revealed sizable differences in cancer survival rates between countries.
In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).
The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.
This indicates major deficiencies in managing this largely curable disease, according to researchers.
Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.
Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.
The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.
The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.
Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.
Adult leukemia
For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.
Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.
ALL in children
For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.
However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.
The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.
Solid tumor malignancies
The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.
Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.
Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.
Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.
“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”
“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”
Credit: Bill Branson
A large, international study has revealed sizable differences in cancer survival rates between countries.
In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).
The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.
This indicates major deficiencies in managing this largely curable disease, according to researchers.
Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.
Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.
The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.
The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.
Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.
Adult leukemia
For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.
Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.
ALL in children
For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.
However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.
The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.
Solid tumor malignancies
The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.
Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.
Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.
Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.
“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”
“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”
Ponatinib approved in Australia
The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.
The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.
Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.
Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.
The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.
The PACE trial
The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.
The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.
In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.
In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.
The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.
Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).
Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.
Safety concerns
Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.
The drug went back on the market last January, with new safety measures in place.
Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.
The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.
The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.
Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.
Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.
The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.
The PACE trial
The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.
The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.
In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.
In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.
The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.
Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).
Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.
Safety concerns
Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.
The drug went back on the market last January, with new safety measures in place.
Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.
The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.
The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.
Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.
Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.
The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.
The PACE trial
The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.
The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.
In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.
In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.
The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.
Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).
Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.
Safety concerns
Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.
The drug went back on the market last January, with new safety measures in place.
Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.
Protein inhibits HSC engraftment
in the bone marrow
Researchers say they have identified a protein that plays a key role in regulating hematopoietic stem cell (HSC) engraftment.
Experiments revealed that protein tyrosine phosphatase-sigma (PTP-sigma) suppresses normal HSC engraftment capacity, but targeted inhibition of
PTP-sigma can substantially improve mouse and human HSC engraftment.
The researchers described these findings in The Journal of Clinical Investigation.
Mamle Quarmyne, a graduate student at the University of California, Los Angeles, and her colleagues first found that PTP-sigma is expressed on a high percentage of mouse and human HSCs.
When the team deleted PTP-sigma in mice, they observed a marked increase in HSCs’ ability to engraft.
When they selected human HSCs that did not express PTP-sigma and transplanted these cells into immune-deficient mice, the researchers observed a 15-fold increase in HSC engraftment.
The team also discovered that PTP-sigma regulates HSC function by suppressing a protein called RAC1, which is known to promote HSC engraftment.
“These findings have tremendous therapeutic potential, since we have identified a new receptor on HSCs, PTP-sigma, which can be specifically targeted as a means to potently increase the engraftment of transplanted HSCs in patients,” said John P. Chute, MD, of the University of California, Los Angeles.
“This approach can also potentially accelerate hematologic recovery in cancer patients receiving chemotherapy and/or radiation, which also suppress the blood and immune systems.”
Now, the researchers are testing small molecules for their ability to inhibit PTP-sigma on HSCs. If these studies are successful, the team aims to translate these findings into clinical trials in the near future.
in the bone marrow
Researchers say they have identified a protein that plays a key role in regulating hematopoietic stem cell (HSC) engraftment.
Experiments revealed that protein tyrosine phosphatase-sigma (PTP-sigma) suppresses normal HSC engraftment capacity, but targeted inhibition of
PTP-sigma can substantially improve mouse and human HSC engraftment.
The researchers described these findings in The Journal of Clinical Investigation.
Mamle Quarmyne, a graduate student at the University of California, Los Angeles, and her colleagues first found that PTP-sigma is expressed on a high percentage of mouse and human HSCs.
When the team deleted PTP-sigma in mice, they observed a marked increase in HSCs’ ability to engraft.
When they selected human HSCs that did not express PTP-sigma and transplanted these cells into immune-deficient mice, the researchers observed a 15-fold increase in HSC engraftment.
The team also discovered that PTP-sigma regulates HSC function by suppressing a protein called RAC1, which is known to promote HSC engraftment.
“These findings have tremendous therapeutic potential, since we have identified a new receptor on HSCs, PTP-sigma, which can be specifically targeted as a means to potently increase the engraftment of transplanted HSCs in patients,” said John P. Chute, MD, of the University of California, Los Angeles.
“This approach can also potentially accelerate hematologic recovery in cancer patients receiving chemotherapy and/or radiation, which also suppress the blood and immune systems.”
Now, the researchers are testing small molecules for their ability to inhibit PTP-sigma on HSCs. If these studies are successful, the team aims to translate these findings into clinical trials in the near future.
in the bone marrow
Researchers say they have identified a protein that plays a key role in regulating hematopoietic stem cell (HSC) engraftment.
Experiments revealed that protein tyrosine phosphatase-sigma (PTP-sigma) suppresses normal HSC engraftment capacity, but targeted inhibition of
PTP-sigma can substantially improve mouse and human HSC engraftment.
The researchers described these findings in The Journal of Clinical Investigation.
Mamle Quarmyne, a graduate student at the University of California, Los Angeles, and her colleagues first found that PTP-sigma is expressed on a high percentage of mouse and human HSCs.
When the team deleted PTP-sigma in mice, they observed a marked increase in HSCs’ ability to engraft.
When they selected human HSCs that did not express PTP-sigma and transplanted these cells into immune-deficient mice, the researchers observed a 15-fold increase in HSC engraftment.
The team also discovered that PTP-sigma regulates HSC function by suppressing a protein called RAC1, which is known to promote HSC engraftment.
“These findings have tremendous therapeutic potential, since we have identified a new receptor on HSCs, PTP-sigma, which can be specifically targeted as a means to potently increase the engraftment of transplanted HSCs in patients,” said John P. Chute, MD, of the University of California, Los Angeles.
“This approach can also potentially accelerate hematologic recovery in cancer patients receiving chemotherapy and/or radiation, which also suppress the blood and immune systems.”
Now, the researchers are testing small molecules for their ability to inhibit PTP-sigma on HSCs. If these studies are successful, the team aims to translate these findings into clinical trials in the near future.
CAR T-cell therapy gets breakthrough designation
Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.
Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.
Credit: Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, to treat patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Breakthrough designation is designed to help accelerate the development and review of new drugs for serious or life-threatening conditions.
The designation comes with potential benefits, including intensive FDA guidance and eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
The FDA recently granted JCAR015 orphan designation to treat ALL as well.
JCAR015 consists of autologous T cells expressing a CD19-specific, CD28/CD3z CAR. The treatment has shown promise in an ongoing phase 1 trial of patients with B-cell ALL.
Initial results from this study were published in Science Translational Medicine last year and in February. Updated results were presented at the AACR Annual Meeting in April.
At that point, the researchers had enrolled 22 adult patients with relapsed or refractory B-ALL who were minimal residual disease-positive or were in first complete remission at enrollment. Patients in complete remission were monitored and only received JCAR015 if they relapsed.
The remaining patients received re-induction chemotherapy (physician’s choice), followed by an infusion of JCAR015. After treatment, patients could receive allogeneic transplant, a different salvage therapy, or monitoring.
Eighty-two percent of patients achieved a complete response to JCAR015. The average time to complete response was about 24.5 days.
Twelve of the responders were eligible for transplant. Of the 8 patients who ultimately underwent transplant and survived, 1 relapsed, but the rest remained in remission.
Ten patients had died at the time of the AACR presentation. Six deaths were a result of disease relapse or progression, and 2 patients died of complications from stem cell transplant.
The 2 remaining deaths prompted a temporary suspension of enrollment in this trial. Those deaths were related to complications from cytokine release syndrome. One patient died of cardiovascular disease, and the other died following persistent seizure activity.
So researchers at the Memorial Sloan-Kettering Cancer Center, where the trial is being conducted, reviewed these cases. The results prompted them to amend trial enrollment criteria and dosing recommendations. Now, patients with cardiac disease are ineligible to receive JCAR015.
And the T-cell dose a patient receives will depend on the extent of his or her disease. The hope is that this will reduce the risk of cytokine release syndrome and any resulting seizures. The researchers also noted that the monoclonal antibody tocilizumab has proven effective in treating cytokine release syndrome.
In addition to this trial, JCAR015 is under investigation at Memorial Sloan-Kettering Cancer Center in a phase 1 trial of patients with relapsed and refractory non-Hodgkin lymphoma.
Two other CAR T-cell product candidates under development by the same company, Juno Therapeutics, Inc., are being tested in clinical trials as well. JCAR017 is under investigation at Seattle Children’s Hospital for relapsed/refractory CD19-positive pediatric leukemia.
JCAR014 is being tested for refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and ALL at the Fred Hutchinson Cancer Research Center. Data on these programs are set to be presented at the 56th ASH Annual Meeting next week in San Francisco.
A new treatment option for elderly AML patients?
Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML.
Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML.
Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML.
More education on SCD needed in sub-Saharan Africa
and a normal one
Credit: Betty Pace
Aggressive public health campaigns are needed to educate people in sub-Saharan Africa about sickle cell disease (SCD), according to a professor of health studies.
William Ebomoyi, PhD, of Chicago State University in Illinois, investigated the prevalence of SCD in sub-Saharan Africa, assessed the physical and emotional ramifications of the disease, evaluated ethical and legal issues related to SCD, and assessed the socio-cultural implications of the disease.
He reported his findings in the International Journal of Medical Engineering and Informatics.
Dr Ebomoyi explained that SCD occurs from a change in valine to glutamine substitution in the sixth amino acid position of the beta globin chain. If one of the two beta globin genes is affected, a person simply has sickle cell trait (SCT), but if both genes are involved, the person has SCD.
If two people with SCT decide to have a child, there is a 50% chance that child will have SCT, a 25% chance the child will have SCD, and a 25% chance the child will have neither condition. If one parent has SCT, there is a 50% chance the child will have SCT.
In some communities in sub-Saharan Africa, up to 2% of all children are born with SCD. And the prevalence of SCT ranges from 10% to 40% across equatorial Africa.
Dr Ebomoyi said early screening to identify infants with SCD is needed, as life-threatening complications can occur within the first 3 years of life. Unfortunately, the method of choice for SCD screening—cellulose acetate accompanied by citrate agar electrophoresis—is only available in two sub-Saharan African nations—South Africa and Ghana.
Similarly, innovative SCD treatment techniques have not been introduced in sub-Saharan African nations. There are not enough well-trained physicians, Dr Ebomoyi said. In fact, many SCD patients are treated improperly by traditional African healers.
Furthermore, aside from Senegal and Liberia, sub-Saharan African nations spend less than 10% of their gross domestic product on healthcare. And inadequate funding plays a major role in the high prevalence of SCD in these nations.
For all these reasons, it is important to raise awareness in sub-Saharan Africa about SCD, according to Dr Ebomoyi. He said members of the public should be aware of how they can pass SCD down to their children and inform their partners if they have SCT prior to conceiving a child.
He added that sickle cell education programs should be integrated into the curriculum of elementary, secondary, and tertiary academic institutions.
The abstract of this article, “Ethical, legal, social, and financial implications of neonatal screening for sickle cell anaemia in Sub-Sahara Africa in the age of genomic science,” can be found on the Inderscience Publishers website.
and a normal one
Credit: Betty Pace
Aggressive public health campaigns are needed to educate people in sub-Saharan Africa about sickle cell disease (SCD), according to a professor of health studies.
William Ebomoyi, PhD, of Chicago State University in Illinois, investigated the prevalence of SCD in sub-Saharan Africa, assessed the physical and emotional ramifications of the disease, evaluated ethical and legal issues related to SCD, and assessed the socio-cultural implications of the disease.
He reported his findings in the International Journal of Medical Engineering and Informatics.
Dr Ebomoyi explained that SCD occurs from a change in valine to glutamine substitution in the sixth amino acid position of the beta globin chain. If one of the two beta globin genes is affected, a person simply has sickle cell trait (SCT), but if both genes are involved, the person has SCD.
If two people with SCT decide to have a child, there is a 50% chance that child will have SCT, a 25% chance the child will have SCD, and a 25% chance the child will have neither condition. If one parent has SCT, there is a 50% chance the child will have SCT.
In some communities in sub-Saharan Africa, up to 2% of all children are born with SCD. And the prevalence of SCT ranges from 10% to 40% across equatorial Africa.
Dr Ebomoyi said early screening to identify infants with SCD is needed, as life-threatening complications can occur within the first 3 years of life. Unfortunately, the method of choice for SCD screening—cellulose acetate accompanied by citrate agar electrophoresis—is only available in two sub-Saharan African nations—South Africa and Ghana.
Similarly, innovative SCD treatment techniques have not been introduced in sub-Saharan African nations. There are not enough well-trained physicians, Dr Ebomoyi said. In fact, many SCD patients are treated improperly by traditional African healers.
Furthermore, aside from Senegal and Liberia, sub-Saharan African nations spend less than 10% of their gross domestic product on healthcare. And inadequate funding plays a major role in the high prevalence of SCD in these nations.
For all these reasons, it is important to raise awareness in sub-Saharan Africa about SCD, according to Dr Ebomoyi. He said members of the public should be aware of how they can pass SCD down to their children and inform their partners if they have SCT prior to conceiving a child.
He added that sickle cell education programs should be integrated into the curriculum of elementary, secondary, and tertiary academic institutions.
The abstract of this article, “Ethical, legal, social, and financial implications of neonatal screening for sickle cell anaemia in Sub-Sahara Africa in the age of genomic science,” can be found on the Inderscience Publishers website.
and a normal one
Credit: Betty Pace
Aggressive public health campaigns are needed to educate people in sub-Saharan Africa about sickle cell disease (SCD), according to a professor of health studies.
William Ebomoyi, PhD, of Chicago State University in Illinois, investigated the prevalence of SCD in sub-Saharan Africa, assessed the physical and emotional ramifications of the disease, evaluated ethical and legal issues related to SCD, and assessed the socio-cultural implications of the disease.
He reported his findings in the International Journal of Medical Engineering and Informatics.
Dr Ebomoyi explained that SCD occurs from a change in valine to glutamine substitution in the sixth amino acid position of the beta globin chain. If one of the two beta globin genes is affected, a person simply has sickle cell trait (SCT), but if both genes are involved, the person has SCD.
If two people with SCT decide to have a child, there is a 50% chance that child will have SCT, a 25% chance the child will have SCD, and a 25% chance the child will have neither condition. If one parent has SCT, there is a 50% chance the child will have SCT.
In some communities in sub-Saharan Africa, up to 2% of all children are born with SCD. And the prevalence of SCT ranges from 10% to 40% across equatorial Africa.
Dr Ebomoyi said early screening to identify infants with SCD is needed, as life-threatening complications can occur within the first 3 years of life. Unfortunately, the method of choice for SCD screening—cellulose acetate accompanied by citrate agar electrophoresis—is only available in two sub-Saharan African nations—South Africa and Ghana.
Similarly, innovative SCD treatment techniques have not been introduced in sub-Saharan African nations. There are not enough well-trained physicians, Dr Ebomoyi said. In fact, many SCD patients are treated improperly by traditional African healers.
Furthermore, aside from Senegal and Liberia, sub-Saharan African nations spend less than 10% of their gross domestic product on healthcare. And inadequate funding plays a major role in the high prevalence of SCD in these nations.
For all these reasons, it is important to raise awareness in sub-Saharan Africa about SCD, according to Dr Ebomoyi. He said members of the public should be aware of how they can pass SCD down to their children and inform their partners if they have SCT prior to conceiving a child.
He added that sickle cell education programs should be integrated into the curriculum of elementary, secondary, and tertiary academic institutions.
The abstract of this article, “Ethical, legal, social, and financial implications of neonatal screening for sickle cell anaemia in Sub-Sahara Africa in the age of genomic science,” can be found on the Inderscience Publishers website.