Hematology Times

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Micrograph showing
multiple myeloma

Preclinical research published in Oncotarget has provided new insights regarding how the protein EZH2 affects the development of multiple myeloma (MM) and reinforces the idea that EZH2 inhibition may be a way to treat MM.

Previous research by the same group suggested that EZH2 is a potential therapeutic target in MM.

With the current study, the group further investigated the anti-myeloma mechanisms mediated by EZH2 inhibition.

They found that targeting EZH2 with an agent known as UNC1999 reduces the expression of 4 MM-associated oncogenes—IRF-4, XBP-1, PRDM1/BLIMP-1, and c-MYC.

“The role of oncogenes in the development of cancer is to potentiate the survival of the cancer cell, which, instead of undergoing cell death, as is usually the case when the cell is not functioning properly, continues to divide and proliferate,” said study author Helena Jernberg-Wiklund, PhD, of Uppsala University in Uppsala, Sweden.

“In our study, we identified 4 oncogenes that showed lower activity in cells treated with the EZH2 inhibitor as compared to control-treated cells. All 4 genes have previously been shown to be associated with the development of multiple myeloma. This confirms our previous findings that inhibition of EZH2 could be used as a means to treat multiple myeloma.”

However, the researchers were puzzled by the fact that inhibition of EZH2 could decrease the activity of the oncogenes.

The chemical histone modification performed by EZH2 leads to decreased activity of affected genes. Therefore, inhibition of EZH2 should result in a reduced level of chemical modifications, which, in turn, should result in increased gene activity.

“The answer is that there are other genetic factors involved, called microRNAs,” Dr Jernberg-Wiklund said. “In the cells treated with the EZH2 inhibitor, we found 2 microRNA genes with increased activity, and we believe that the oncogenes are regulated by these microRNAs.”

“What happens then is that, when EZH2 is inhibited, there is a reduced histone modification at the microRNA genes. This leads to an increased synthesis of the microRNAs, which, in turn, decreases the activity of the oncogenes. This is a completely new mechanism for EZH2 action.”

The microRNAs the researchers identified are miR-125a-3p and miR-320c. The team found that miR-125a-3p and miR-320c were targets of EZH2 and H3K27me3 in MM cell lines and primary cells.

The researchers said these results support their previous work suggesting EZH2 could be a therapeutic target in MM.

Micrograph showing
multiple myeloma

Preclinical research published in Oncotarget has provided new insights regarding how the protein EZH2 affects the development of multiple myeloma (MM) and reinforces the idea that EZH2 inhibition may be a way to treat MM.

Previous research by the same group suggested that EZH2 is a potential therapeutic target in MM.

With the current study, the group further investigated the anti-myeloma mechanisms mediated by EZH2 inhibition.

They found that targeting EZH2 with an agent known as UNC1999 reduces the expression of 4 MM-associated oncogenes—IRF-4, XBP-1, PRDM1/BLIMP-1, and c-MYC.

“The role of oncogenes in the development of cancer is to potentiate the survival of the cancer cell, which, instead of undergoing cell death, as is usually the case when the cell is not functioning properly, continues to divide and proliferate,” said study author Helena Jernberg-Wiklund, PhD, of Uppsala University in Uppsala, Sweden.

“In our study, we identified 4 oncogenes that showed lower activity in cells treated with the EZH2 inhibitor as compared to control-treated cells. All 4 genes have previously been shown to be associated with the development of multiple myeloma. This confirms our previous findings that inhibition of EZH2 could be used as a means to treat multiple myeloma.”

However, the researchers were puzzled by the fact that inhibition of EZH2 could decrease the activity of the oncogenes.

The chemical histone modification performed by EZH2 leads to decreased activity of affected genes. Therefore, inhibition of EZH2 should result in a reduced level of chemical modifications, which, in turn, should result in increased gene activity.

“The answer is that there are other genetic factors involved, called microRNAs,” Dr Jernberg-Wiklund said. “In the cells treated with the EZH2 inhibitor, we found 2 microRNA genes with increased activity, and we believe that the oncogenes are regulated by these microRNAs.”

“What happens then is that, when EZH2 is inhibited, there is a reduced histone modification at the microRNA genes. This leads to an increased synthesis of the microRNAs, which, in turn, decreases the activity of the oncogenes. This is a completely new mechanism for EZH2 action.”

The microRNAs the researchers identified are miR-125a-3p and miR-320c. The team found that miR-125a-3p and miR-320c were targets of EZH2 and H3K27me3 in MM cell lines and primary cells.

The researchers said these results support their previous work suggesting EZH2 could be a therapeutic target in MM.

Micrograph showing
multiple myeloma

Preclinical research published in Oncotarget has provided new insights regarding how the protein EZH2 affects the development of multiple myeloma (MM) and reinforces the idea that EZH2 inhibition may be a way to treat MM.

Previous research by the same group suggested that EZH2 is a potential therapeutic target in MM.

With the current study, the group further investigated the anti-myeloma mechanisms mediated by EZH2 inhibition.

They found that targeting EZH2 with an agent known as UNC1999 reduces the expression of 4 MM-associated oncogenes—IRF-4, XBP-1, PRDM1/BLIMP-1, and c-MYC.

“The role of oncogenes in the development of cancer is to potentiate the survival of the cancer cell, which, instead of undergoing cell death, as is usually the case when the cell is not functioning properly, continues to divide and proliferate,” said study author Helena Jernberg-Wiklund, PhD, of Uppsala University in Uppsala, Sweden.

“In our study, we identified 4 oncogenes that showed lower activity in cells treated with the EZH2 inhibitor as compared to control-treated cells. All 4 genes have previously been shown to be associated with the development of multiple myeloma. This confirms our previous findings that inhibition of EZH2 could be used as a means to treat multiple myeloma.”

However, the researchers were puzzled by the fact that inhibition of EZH2 could decrease the activity of the oncogenes.

The chemical histone modification performed by EZH2 leads to decreased activity of affected genes. Therefore, inhibition of EZH2 should result in a reduced level of chemical modifications, which, in turn, should result in increased gene activity.

“The answer is that there are other genetic factors involved, called microRNAs,” Dr Jernberg-Wiklund said. “In the cells treated with the EZH2 inhibitor, we found 2 microRNA genes with increased activity, and we believe that the oncogenes are regulated by these microRNAs.”

“What happens then is that, when EZH2 is inhibited, there is a reduced histone modification at the microRNA genes. This leads to an increased synthesis of the microRNAs, which, in turn, decreases the activity of the oncogenes. This is a completely new mechanism for EZH2 action.”

The microRNAs the researchers identified are miR-125a-3p and miR-320c. The team found that miR-125a-3p and miR-320c were targets of EZH2 and H3K27me3 in MM cell lines and primary cells.

The researchers said these results support their previous work suggesting EZH2 could be a therapeutic target in MM.

Cows in Karnataka, India
Photo by Ilya Mauter

The goal of eliminating malaria in countries like India could be more achievable if mosquito-control efforts take into account the relationship between mosquitoes and cattle, according to an international team of researchers.

The group analyzed 2 mosquito

species found in Odisha, the state with the highest number of malaria cases in

India, and found that both species fed on cattle as well as humans.

“In many parts of the world, the mosquitoes responsible for transmitting malaria are specialist feeders on humans and often rest within human houses,” said Matthew Thomas, PhD, of Pennsylvania State University in University Park, Pennsylvania.

“We found that, in an area of India that has a high burden of malaria, most of the mosquitoes that are known to transmit malaria rest in cattle sheds and feed on both cows and humans.”

Dr Thomas and his colleagues reported these findings in Scientific Reports.

According to the researchers, cattle sheds in India are often next to, and sometimes even share a wall with, human houses. However, current malaria control efforts are restricted to domestic dwellings only.

“Given this cattle-shed ‘refuge’ for mosquitoes, focusing only on humans with regard to malaria control is a bit like treating the tip of an iceberg,” said study author Jessica Waite, PhD, also of Pennsylvania State University.

She, Dr Thomas, and their colleagues determined the importance of cows in the malaria-control problem by capturing adult mosquitoes in different habitats within 6 villages in Odisha state—which has the highest number of malaria cases in the country—and noting where the mosquitoes had been resting.

The team then used molecular techniques to determine which species of mosquitoes had been captured and which hosts they had been feeding on.

The researchers collected 1774 Anopheles culicifacies mosquitoes and 169 Anopheles fluviatilis mosquitoes across all study sites.

Both species were denser in cattle sheds than in human dwellings, and both were feeding on humans as well as cattle.

Next, the researchers used their field-collected data to help build a computer model that simulated the life of an adult mosquito. The team used the model to explore how best to control the mosquitoes to have maximum impact on malaria transmission in these villages.

“Our model analysis suggests that conventional control tools—such as insecticide-treated bed nets and indoor insecticide sprays—are less effective when mosquitoes exhibit ‘zoophilic’ behaviors (having an attraction to nonhuman animals),” Dr Thomas said.

“However, extending controls to better target the zoophilic mosquitoes—for example, by broadening coverage of non-repellant insecticide sprays to include cattle sheds—could help reduce transmission dramatically.”

Dr Waite added that the model suggests very little cattle-based vector control effort would be required to drive malaria transmission in the region to elimination.

“We show that directing even modest amounts of effort to specifically increase mosquito mortality associated with zoophilic behavior can shift the balance towards elimination,” she said.

“Understanding the dynamic between humans, cattle, and mosquitoes could have major implications for malaria control policy and practice, not only in India, but in other areas where transmission is sustained by zoophilic vectors,” Dr Thomas said.

“Specifically, optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target set by the World Health Organization, which aims to decrease malaria cases globally by 90% compared to 2015 levels and eliminate malaria in at least 35 additional countries by 2030.”

Cows in Karnataka, India
Photo by Ilya Mauter

The goal of eliminating malaria in countries like India could be more achievable if mosquito-control efforts take into account the relationship between mosquitoes and cattle, according to an international team of researchers.

The group analyzed 2 mosquito

species found in Odisha, the state with the highest number of malaria cases in

India, and found that both species fed on cattle as well as humans.

“In many parts of the world, the mosquitoes responsible for transmitting malaria are specialist feeders on humans and often rest within human houses,” said Matthew Thomas, PhD, of Pennsylvania State University in University Park, Pennsylvania.

“We found that, in an area of India that has a high burden of malaria, most of the mosquitoes that are known to transmit malaria rest in cattle sheds and feed on both cows and humans.”

Dr Thomas and his colleagues reported these findings in Scientific Reports.

According to the researchers, cattle sheds in India are often next to, and sometimes even share a wall with, human houses. However, current malaria control efforts are restricted to domestic dwellings only.

“Given this cattle-shed ‘refuge’ for mosquitoes, focusing only on humans with regard to malaria control is a bit like treating the tip of an iceberg,” said study author Jessica Waite, PhD, also of Pennsylvania State University.

She, Dr Thomas, and their colleagues determined the importance of cows in the malaria-control problem by capturing adult mosquitoes in different habitats within 6 villages in Odisha state—which has the highest number of malaria cases in the country—and noting where the mosquitoes had been resting.

The team then used molecular techniques to determine which species of mosquitoes had been captured and which hosts they had been feeding on.

The researchers collected 1774 Anopheles culicifacies mosquitoes and 169 Anopheles fluviatilis mosquitoes across all study sites.

Both species were denser in cattle sheds than in human dwellings, and both were feeding on humans as well as cattle.

Next, the researchers used their field-collected data to help build a computer model that simulated the life of an adult mosquito. The team used the model to explore how best to control the mosquitoes to have maximum impact on malaria transmission in these villages.

“Our model analysis suggests that conventional control tools—such as insecticide-treated bed nets and indoor insecticide sprays—are less effective when mosquitoes exhibit ‘zoophilic’ behaviors (having an attraction to nonhuman animals),” Dr Thomas said.

“However, extending controls to better target the zoophilic mosquitoes—for example, by broadening coverage of non-repellant insecticide sprays to include cattle sheds—could help reduce transmission dramatically.”

Dr Waite added that the model suggests very little cattle-based vector control effort would be required to drive malaria transmission in the region to elimination.

“We show that directing even modest amounts of effort to specifically increase mosquito mortality associated with zoophilic behavior can shift the balance towards elimination,” she said.

“Understanding the dynamic between humans, cattle, and mosquitoes could have major implications for malaria control policy and practice, not only in India, but in other areas where transmission is sustained by zoophilic vectors,” Dr Thomas said.

“Specifically, optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target set by the World Health Organization, which aims to decrease malaria cases globally by 90% compared to 2015 levels and eliminate malaria in at least 35 additional countries by 2030.”

Cows in Karnataka, India
Photo by Ilya Mauter

The goal of eliminating malaria in countries like India could be more achievable if mosquito-control efforts take into account the relationship between mosquitoes and cattle, according to an international team of researchers.

The group analyzed 2 mosquito

species found in Odisha, the state with the highest number of malaria cases in

India, and found that both species fed on cattle as well as humans.

“In many parts of the world, the mosquitoes responsible for transmitting malaria are specialist feeders on humans and often rest within human houses,” said Matthew Thomas, PhD, of Pennsylvania State University in University Park, Pennsylvania.

“We found that, in an area of India that has a high burden of malaria, most of the mosquitoes that are known to transmit malaria rest in cattle sheds and feed on both cows and humans.”

Dr Thomas and his colleagues reported these findings in Scientific Reports.

According to the researchers, cattle sheds in India are often next to, and sometimes even share a wall with, human houses. However, current malaria control efforts are restricted to domestic dwellings only.

“Given this cattle-shed ‘refuge’ for mosquitoes, focusing only on humans with regard to malaria control is a bit like treating the tip of an iceberg,” said study author Jessica Waite, PhD, also of Pennsylvania State University.

She, Dr Thomas, and their colleagues determined the importance of cows in the malaria-control problem by capturing adult mosquitoes in different habitats within 6 villages in Odisha state—which has the highest number of malaria cases in the country—and noting where the mosquitoes had been resting.

The team then used molecular techniques to determine which species of mosquitoes had been captured and which hosts they had been feeding on.

The researchers collected 1774 Anopheles culicifacies mosquitoes and 169 Anopheles fluviatilis mosquitoes across all study sites.

Both species were denser in cattle sheds than in human dwellings, and both were feeding on humans as well as cattle.

Next, the researchers used their field-collected data to help build a computer model that simulated the life of an adult mosquito. The team used the model to explore how best to control the mosquitoes to have maximum impact on malaria transmission in these villages.

“Our model analysis suggests that conventional control tools—such as insecticide-treated bed nets and indoor insecticide sprays—are less effective when mosquitoes exhibit ‘zoophilic’ behaviors (having an attraction to nonhuman animals),” Dr Thomas said.

“However, extending controls to better target the zoophilic mosquitoes—for example, by broadening coverage of non-repellant insecticide sprays to include cattle sheds—could help reduce transmission dramatically.”

Dr Waite added that the model suggests very little cattle-based vector control effort would be required to drive malaria transmission in the region to elimination.

“We show that directing even modest amounts of effort to specifically increase mosquito mortality associated with zoophilic behavior can shift the balance towards elimination,” she said.

“Understanding the dynamic between humans, cattle, and mosquitoes could have major implications for malaria control policy and practice, not only in India, but in other areas where transmission is sustained by zoophilic vectors,” Dr Thomas said.

“Specifically, optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target set by the World Health Organization, which aims to decrease malaria cases globally by 90% compared to 2015 levels and eliminate malaria in at least 35 additional countries by 2030.”

Hartmut Döhner, MD
Photo courtesy of
University Hospital Ulm

Research published in Nature Genetics suggests a knowledge bank

can reveal the optimal treatment for patients with acute

myeloid leukemia (AML), although more research is needed before such

banks can be used in the clinic.

Researchers built a knowledge

bank using data from 1540 AML patients enrolled in clinical

trials in Germany and Austria.

The bank includes information on genetic features, treatment, and outcomes for each patient.

The researchers used this information to develop models that could predict a patient’s likelihood of remission, relapse, and mortality.

The team then validated those results using data from patients in The Cancer Genome Atlas.

The researchers estimate that up to 1 in 3 AML patients would be prescribed a different treatment regimen if physicians used the knowledge bank approach rather than current practice.

“The knowledge bank approach makes far more detailed and accurate predictions about the likely future course of a patient with AML than what we can make in the clinic at the moment,” said study author Peter Campbell, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“Current guides use a simple set of rules based on only a few genetic findings. For any given patient, using the new tool, we can compare the likely future outcomes under a transplant route versus a standard chemotherapy route. This means that we can make a treatment choice that is personally tailored to the unique features of that particular patient.”

However, the researchers said the knowledge bank approach requires further testing before it can be used to prescribe treatment in AML clinics.

“Our analysis reveals that knowledge banks of up to 10,000 patients would be needed to obtain the precision needed for routine clinical application,” said study author Moritz Gerstung, PhD, of the European Bioinformatics Institute in Hinxton, UK.

“Building knowledge banks is not easy,” added author Hartmut Döhner, MD, of the University of Ulm in Germany. “To get accurate treatment predictions, you need data from thousands of patients and all tumor types.”

“Furthermore, such knowledge banks will need continuous updating as new therapies become approved and available. As genetic testing enters routine clinical practice, there is an opportunity to learn from patients undergoing care in our health systems. Our paper gives the first real evidence that the approach is worthwhile, how it could be used, and what the scale needs to be.”

Hartmut Döhner, MD
Photo courtesy of
University Hospital Ulm

Research published in Nature Genetics suggests a knowledge bank

can reveal the optimal treatment for patients with acute

myeloid leukemia (AML), although more research is needed before such

banks can be used in the clinic.

Researchers built a knowledge

bank using data from 1540 AML patients enrolled in clinical

trials in Germany and Austria.

The bank includes information on genetic features, treatment, and outcomes for each patient.

The researchers used this information to develop models that could predict a patient’s likelihood of remission, relapse, and mortality.

The team then validated those results using data from patients in The Cancer Genome Atlas.

The researchers estimate that up to 1 in 3 AML patients would be prescribed a different treatment regimen if physicians used the knowledge bank approach rather than current practice.

“The knowledge bank approach makes far more detailed and accurate predictions about the likely future course of a patient with AML than what we can make in the clinic at the moment,” said study author Peter Campbell, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“Current guides use a simple set of rules based on only a few genetic findings. For any given patient, using the new tool, we can compare the likely future outcomes under a transplant route versus a standard chemotherapy route. This means that we can make a treatment choice that is personally tailored to the unique features of that particular patient.”

However, the researchers said the knowledge bank approach requires further testing before it can be used to prescribe treatment in AML clinics.

“Our analysis reveals that knowledge banks of up to 10,000 patients would be needed to obtain the precision needed for routine clinical application,” said study author Moritz Gerstung, PhD, of the European Bioinformatics Institute in Hinxton, UK.

“Building knowledge banks is not easy,” added author Hartmut Döhner, MD, of the University of Ulm in Germany. “To get accurate treatment predictions, you need data from thousands of patients and all tumor types.”

“Furthermore, such knowledge banks will need continuous updating as new therapies become approved and available. As genetic testing enters routine clinical practice, there is an opportunity to learn from patients undergoing care in our health systems. Our paper gives the first real evidence that the approach is worthwhile, how it could be used, and what the scale needs to be.”

Hartmut Döhner, MD
Photo courtesy of
University Hospital Ulm

Research published in Nature Genetics suggests a knowledge bank

can reveal the optimal treatment for patients with acute

myeloid leukemia (AML), although more research is needed before such

banks can be used in the clinic.

Researchers built a knowledge

bank using data from 1540 AML patients enrolled in clinical

trials in Germany and Austria.

The bank includes information on genetic features, treatment, and outcomes for each patient.

The researchers used this information to develop models that could predict a patient’s likelihood of remission, relapse, and mortality.

The team then validated those results using data from patients in The Cancer Genome Atlas.

The researchers estimate that up to 1 in 3 AML patients would be prescribed a different treatment regimen if physicians used the knowledge bank approach rather than current practice.

“The knowledge bank approach makes far more detailed and accurate predictions about the likely future course of a patient with AML than what we can make in the clinic at the moment,” said study author Peter Campbell, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“Current guides use a simple set of rules based on only a few genetic findings. For any given patient, using the new tool, we can compare the likely future outcomes under a transplant route versus a standard chemotherapy route. This means that we can make a treatment choice that is personally tailored to the unique features of that particular patient.”

However, the researchers said the knowledge bank approach requires further testing before it can be used to prescribe treatment in AML clinics.

“Our analysis reveals that knowledge banks of up to 10,000 patients would be needed to obtain the precision needed for routine clinical application,” said study author Moritz Gerstung, PhD, of the European Bioinformatics Institute in Hinxton, UK.

“Building knowledge banks is not easy,” added author Hartmut Döhner, MD, of the University of Ulm in Germany. “To get accurate treatment predictions, you need data from thousands of patients and all tumor types.”

“Furthermore, such knowledge banks will need continuous updating as new therapies become approved and available. As genetic testing enters routine clinical practice, there is an opportunity to learn from patients undergoing care in our health systems. Our paper gives the first real evidence that the approach is worthwhile, how it could be used, and what the scale needs to be.”

Sleeping newborn
Photo by Bertrand Devouard

Data from hospitals in 29 European countries suggest that healthcare-associated infections (HAIs) reported in children occur most often in infants younger than 12 months of age.

And the prevalence of infection is highest for children in intensive care units (ICUs).

Walter Zingg, MD, of Imperial College London in the UK, and his colleagues conducted this research and detailed the results in The Lancet Infectious Diseases.

The researchers analyzed data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey of HAIs and antimicrobial use in European acute care hospitals.

The data encompassed 17,273 children and adolescents (ages 0 to 18) treated at 1149 hospitals in 29 European countries* from May 2011 to November 2012.

During that time, there were 770 infections reported in 726 children and adolescents.

The researchers found that most HAIs (77%) occurred in infants younger than 12 months. And the prevalence of infections was highest in pediatric ICUs and neonatal ICUs—15.5% and 10.7%, respectively.

Bloodstream infections were the most common type (45%), followed by lower respiratory tract infections (22%); gastrointestinal infections (8%); eye, ear, nose, and throat infections (7%); urinary tract infections (5%); and surgical-site infections (4%).

Analyses suggested that independent risk factors for infection included being younger than 12 months, having a fatal disease, a prolonged length of hospital stay, and receiving treatment with invasive medical devices.

The researchers said a pan-European program is urgently needed to prevent and reduce the unacceptably high rates of HAIs in children in Europe, with a focus in neonatal and pediatric ICUs and addressing the issues related to healthcare-associated bloodstream infections.

The team said this is the largest multinational study describing HAIs in children thus far.

A second point prevalence survey is ongoing in Europe, and its results are expected to be published by the ECDC after 2017.

*Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, and the UK.

Sleeping newborn
Photo by Bertrand Devouard

Data from hospitals in 29 European countries suggest that healthcare-associated infections (HAIs) reported in children occur most often in infants younger than 12 months of age.

And the prevalence of infection is highest for children in intensive care units (ICUs).

Walter Zingg, MD, of Imperial College London in the UK, and his colleagues conducted this research and detailed the results in The Lancet Infectious Diseases.

The researchers analyzed data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey of HAIs and antimicrobial use in European acute care hospitals.

The data encompassed 17,273 children and adolescents (ages 0 to 18) treated at 1149 hospitals in 29 European countries* from May 2011 to November 2012.

During that time, there were 770 infections reported in 726 children and adolescents.

The researchers found that most HAIs (77%) occurred in infants younger than 12 months. And the prevalence of infections was highest in pediatric ICUs and neonatal ICUs—15.5% and 10.7%, respectively.

Bloodstream infections were the most common type (45%), followed by lower respiratory tract infections (22%); gastrointestinal infections (8%); eye, ear, nose, and throat infections (7%); urinary tract infections (5%); and surgical-site infections (4%).

Analyses suggested that independent risk factors for infection included being younger than 12 months, having a fatal disease, a prolonged length of hospital stay, and receiving treatment with invasive medical devices.

The researchers said a pan-European program is urgently needed to prevent and reduce the unacceptably high rates of HAIs in children in Europe, with a focus in neonatal and pediatric ICUs and addressing the issues related to healthcare-associated bloodstream infections.

The team said this is the largest multinational study describing HAIs in children thus far.

A second point prevalence survey is ongoing in Europe, and its results are expected to be published by the ECDC after 2017.

*Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, and the UK.

Sleeping newborn
Photo by Bertrand Devouard

Data from hospitals in 29 European countries suggest that healthcare-associated infections (HAIs) reported in children occur most often in infants younger than 12 months of age.

And the prevalence of infection is highest for children in intensive care units (ICUs).

Walter Zingg, MD, of Imperial College London in the UK, and his colleagues conducted this research and detailed the results in The Lancet Infectious Diseases.

The researchers analyzed data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey of HAIs and antimicrobial use in European acute care hospitals.

The data encompassed 17,273 children and adolescents (ages 0 to 18) treated at 1149 hospitals in 29 European countries* from May 2011 to November 2012.

During that time, there were 770 infections reported in 726 children and adolescents.

The researchers found that most HAIs (77%) occurred in infants younger than 12 months. And the prevalence of infections was highest in pediatric ICUs and neonatal ICUs—15.5% and 10.7%, respectively.

Bloodstream infections were the most common type (45%), followed by lower respiratory tract infections (22%); gastrointestinal infections (8%); eye, ear, nose, and throat infections (7%); urinary tract infections (5%); and surgical-site infections (4%).

Analyses suggested that independent risk factors for infection included being younger than 12 months, having a fatal disease, a prolonged length of hospital stay, and receiving treatment with invasive medical devices.

The researchers said a pan-European program is urgently needed to prevent and reduce the unacceptably high rates of HAIs in children in Europe, with a focus in neonatal and pediatric ICUs and addressing the issues related to healthcare-associated bloodstream infections.

The team said this is the largest multinational study describing HAIs in children thus far.

A second point prevalence survey is ongoing in Europe, and its results are expected to be published by the ECDC after 2017.

*Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, and the UK.

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.