Lab mice
Photo by Aaron Logan

Preclinical research suggests that targeting 2 kinases may provide an approach to treating graft-vs-host-disease (GVHD) that does not compromise the tumor-fighting capabilities of the immune system.

Researchers said that dual inhibition of Aurora kinase A and JAK2, attenuating CD28 costimulation and IL-6-mediated signal transduction, respectively, can fight GVHD without destroying potential antitumor cytotoxic T lymphocyte (CTL) responses.

The team detailed these findings in Science Translational Medicine.

“It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD,” said study author Brian C. Betts, MD, of H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“However, drugs that inhibit either protein alone do not completely prevent GVHD. We hypothesized that co-treatment with drugs that target both Aurora kinase A and JAK2 could prevent GVHD better than either drug alone.”

In fact, Dr Betts and his colleagues engineered and tested 2 compounds that inhibit both Aurora kinase A and JAK2—AJI-100 and AJI-214.

The team then compared the AJI analogs to the Aurora kinase A inhibitor alisertib, the JAK2 inhibitor TG101348, the combination of alisertib and TG101348, and dimethyl sulfoxide (DMSO) control.

The researchers first found that AJI-214 and AJI-100 “exerted significant suppression of T cells” in vitro, suppressing alloreactive T-cell proliferation with a potency that was similar to that of alisertib and TG101348 in combination.

The team noted that inhibition of Aurora kinase A and JAK2—with either AJI analog or alisertib and TG101348 in combination—significantly reduced alloreactive conventional T cells (Tconv) and helper T cells (TH1 and TH17) but permitted the differentiation of inducible regulatory T cells (iTregs).

In fact, the researchers said that dual inhibition of Aurora kinase A and JAK2 supports potent CD39+ iTregs. They observed higher CD39 cell surface density among AJI-214–treated iTregs, which resulted in improved scavenging of extracellular adenosine triphosphate, when compared to DMSO-treated iTregs.

The team then tested AJI-100 in mouse models of GVHD, as this drug has better bioavailability than AJI-214.

AJI-100 significantly improved the overall survival of the mice and reduced the severity of GVHD, compared to vehicle control (P=0.003).

In comparison, alisertib and TG101348 in combination significantly delayed the onset and severity of GVHD when compared to vehicle or TG101348 alone (P<0.0001 and P=0.0001). But the combination did not significantly improve survival in the mice.

Next, the researchers tested the effects of AJI-100 on CTLs by generating human antitumor CTLs in xenotransplanted mice. The mice received AJI-100 or vehicle control, as well as irradiated U937 cells. Unvaccinated, xenotransplanted mice served as negative controls.

The team said AJI-100 did not inhibit CTL generation because CD8+ CTLs from AJI-100–treated and vehicle-treated mice demonstrated similarly enhanced killing capacity against U937 targets in vitro, when compared to unvaccinated controls.

Additional experiments in mice showed that AJI-100 significantly increases the ratio of Tregs to activated Tconv while eliminating TH17 and TH1 cells.

The researchers therefore concluded that inhibiting CD28 and IL-6 signal transduction pathways in donor T cells may increase the Treg/Tconv ratio, prevent GVHD, and preserve antitumor CTLs.

“This novel prevention strategy warrants further investigation because of its potential to reduce the risk of GVHD and possibly be more effective and selective than commonly used GVHD treatments currently available today,” Dr Betts said.

Lab mice
Photo by Aaron Logan

Preclinical research suggests that targeting 2 kinases may provide an approach to treating graft-vs-host-disease (GVHD) that does not compromise the tumor-fighting capabilities of the immune system.

Researchers said that dual inhibition of Aurora kinase A and JAK2, attenuating CD28 costimulation and IL-6-mediated signal transduction, respectively, can fight GVHD without destroying potential antitumor cytotoxic T lymphocyte (CTL) responses.

The team detailed these findings in Science Translational Medicine.

“It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD,” said study author Brian C. Betts, MD, of H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“However, drugs that inhibit either protein alone do not completely prevent GVHD. We hypothesized that co-treatment with drugs that target both Aurora kinase A and JAK2 could prevent GVHD better than either drug alone.”

In fact, Dr Betts and his colleagues engineered and tested 2 compounds that inhibit both Aurora kinase A and JAK2—AJI-100 and AJI-214.

The team then compared the AJI analogs to the Aurora kinase A inhibitor alisertib, the JAK2 inhibitor TG101348, the combination of alisertib and TG101348, and dimethyl sulfoxide (DMSO) control.

The researchers first found that AJI-214 and AJI-100 “exerted significant suppression of T cells” in vitro, suppressing alloreactive T-cell proliferation with a potency that was similar to that of alisertib and TG101348 in combination.

The team noted that inhibition of Aurora kinase A and JAK2—with either AJI analog or alisertib and TG101348 in combination—significantly reduced alloreactive conventional T cells (Tconv) and helper T cells (TH1 and TH17) but permitted the differentiation of inducible regulatory T cells (iTregs).

In fact, the researchers said that dual inhibition of Aurora kinase A and JAK2 supports potent CD39+ iTregs. They observed higher CD39 cell surface density among AJI-214–treated iTregs, which resulted in improved scavenging of extracellular adenosine triphosphate, when compared to DMSO-treated iTregs.

The team then tested AJI-100 in mouse models of GVHD, as this drug has better bioavailability than AJI-214.

AJI-100 significantly improved the overall survival of the mice and reduced the severity of GVHD, compared to vehicle control (P=0.003).

In comparison, alisertib and TG101348 in combination significantly delayed the onset and severity of GVHD when compared to vehicle or TG101348 alone (P<0.0001 and P=0.0001). But the combination did not significantly improve survival in the mice.

Next, the researchers tested the effects of AJI-100 on CTLs by generating human antitumor CTLs in xenotransplanted mice. The mice received AJI-100 or vehicle control, as well as irradiated U937 cells. Unvaccinated, xenotransplanted mice served as negative controls.

The team said AJI-100 did not inhibit CTL generation because CD8+ CTLs from AJI-100–treated and vehicle-treated mice demonstrated similarly enhanced killing capacity against U937 targets in vitro, when compared to unvaccinated controls.

Additional experiments in mice showed that AJI-100 significantly increases the ratio of Tregs to activated Tconv while eliminating TH17 and TH1 cells.

The researchers therefore concluded that inhibiting CD28 and IL-6 signal transduction pathways in donor T cells may increase the Treg/Tconv ratio, prevent GVHD, and preserve antitumor CTLs.

“This novel prevention strategy warrants further investigation because of its potential to reduce the risk of GVHD and possibly be more effective and selective than commonly used GVHD treatments currently available today,” Dr Betts said.

Lab mice
Photo by Aaron Logan

Preclinical research suggests that targeting 2 kinases may provide an approach to treating graft-vs-host-disease (GVHD) that does not compromise the tumor-fighting capabilities of the immune system.

Researchers said that dual inhibition of Aurora kinase A and JAK2, attenuating CD28 costimulation and IL-6-mediated signal transduction, respectively, can fight GVHD without destroying potential antitumor cytotoxic T lymphocyte (CTL) responses.

The team detailed these findings in Science Translational Medicine.

“It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD,” said study author Brian C. Betts, MD, of H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.

“However, drugs that inhibit either protein alone do not completely prevent GVHD. We hypothesized that co-treatment with drugs that target both Aurora kinase A and JAK2 could prevent GVHD better than either drug alone.”

In fact, Dr Betts and his colleagues engineered and tested 2 compounds that inhibit both Aurora kinase A and JAK2—AJI-100 and AJI-214.

The team then compared the AJI analogs to the Aurora kinase A inhibitor alisertib, the JAK2 inhibitor TG101348, the combination of alisertib and TG101348, and dimethyl sulfoxide (DMSO) control.

The researchers first found that AJI-214 and AJI-100 “exerted significant suppression of T cells” in vitro, suppressing alloreactive T-cell proliferation with a potency that was similar to that of alisertib and TG101348 in combination.

The team noted that inhibition of Aurora kinase A and JAK2—with either AJI analog or alisertib and TG101348 in combination—significantly reduced alloreactive conventional T cells (Tconv) and helper T cells (TH1 and TH17) but permitted the differentiation of inducible regulatory T cells (iTregs).

In fact, the researchers said that dual inhibition of Aurora kinase A and JAK2 supports potent CD39+ iTregs. They observed higher CD39 cell surface density among AJI-214–treated iTregs, which resulted in improved scavenging of extracellular adenosine triphosphate, when compared to DMSO-treated iTregs.

The team then tested AJI-100 in mouse models of GVHD, as this drug has better bioavailability than AJI-214.

AJI-100 significantly improved the overall survival of the mice and reduced the severity of GVHD, compared to vehicle control (P=0.003).

In comparison, alisertib and TG101348 in combination significantly delayed the onset and severity of GVHD when compared to vehicle or TG101348 alone (P<0.0001 and P=0.0001). But the combination did not significantly improve survival in the mice.

Next, the researchers tested the effects of AJI-100 on CTLs by generating human antitumor CTLs in xenotransplanted mice. The mice received AJI-100 or vehicle control, as well as irradiated U937 cells. Unvaccinated, xenotransplanted mice served as negative controls.

The team said AJI-100 did not inhibit CTL generation because CD8+ CTLs from AJI-100–treated and vehicle-treated mice demonstrated similarly enhanced killing capacity against U937 targets in vitro, when compared to unvaccinated controls.

Additional experiments in mice showed that AJI-100 significantly increases the ratio of Tregs to activated Tconv while eliminating TH17 and TH1 cells.

The researchers therefore concluded that inhibiting CD28 and IL-6 signal transduction pathways in donor T cells may increase the Treg/Tconv ratio, prevent GVHD, and preserve antitumor CTLs.

“This novel prevention strategy warrants further investigation because of its potential to reduce the risk of GVHD and possibly be more effective and selective than commonly used GVHD treatments currently available today,” Dr Betts said.

Malaria-carrying mosquito
Photo by James Gathany

Mosquitoes carrying a greater number of malaria-causing parasites may be more likely to cause infection, according to a study published in PLOS Pathogens.

More than 100 years have passed since scientists first discovered that infectious mosquitoes inject malaria parasites when they bite people.

However, it hasn’t been clear whether injecting more parasites with each bite increases a person’s chances of infection or if all infectious bites are equally dangerous.

In the new study, researchers set out to determine whether the number of parasites found in the salivary glands of malaria-carrying mosquitos impacts disease transmission.

Via experiments in mice, the team determined that the more parasites present in a mosquito’s salivary glands, the more likely it was to be infectious and the faster an infection would develop.

“It is surprising that the relationship between parasite density and infectiousness has not been properly investigated before, but the studies are quite complex to carry out,” noted Andrew Blagborough, PhD, of Imperial College London in the UK.

For this study, he and his colleagues set up repeated cycles of infection so that groups of infected mosquitoes containing variable numbers of parasites repeatedly bit sedated mice, transmitting malaria to them under a range of transmission settings.

This allowed the researchers to track how many individual parasites different mosquitoes harbored, how many mice were infected as a result of exposure to them, and how long it took the mice to develop malaria.

The team also analyzed data from human volunteers who were exposed to bites from infectious mosquitoes.

Dissection of these mosquitoes revealed that infection was significantly more likely—and occurred sooner—after bites from mosquitoes with more than 1000 individual parasites in their salivary glands.

By conducting further studies with mice and human volunteers, the researchers were able to provide an explanation for why the malaria vaccine RTS,S is effective only some of the time and why any protection rapidly drops off after 3 years.

The vaccine was less effective when mice or humans were bitten by mosquitoes carrying a greater number of parasites. The researchers think this is because the vaccine can only kill a certain proportion of the parasites and is overwhelmed when the parasite population is too large.

“Vaccine development has come a long way, and this new insight should help future vaccine studies to be tested more rigorously,” said study author Thomas Churcher, PhD, of Imperial College London.

“However, in the end, it is unlikely that one magic bullet will eradicate malaria, and we should continue to seek and apply combinations of strategies for reducing the burden of this disease.”

Malaria-carrying mosquito
Photo by James Gathany

Mosquitoes carrying a greater number of malaria-causing parasites may be more likely to cause infection, according to a study published in PLOS Pathogens.

More than 100 years have passed since scientists first discovered that infectious mosquitoes inject malaria parasites when they bite people.

However, it hasn’t been clear whether injecting more parasites with each bite increases a person’s chances of infection or if all infectious bites are equally dangerous.

In the new study, researchers set out to determine whether the number of parasites found in the salivary glands of malaria-carrying mosquitos impacts disease transmission.

Via experiments in mice, the team determined that the more parasites present in a mosquito’s salivary glands, the more likely it was to be infectious and the faster an infection would develop.

“It is surprising that the relationship between parasite density and infectiousness has not been properly investigated before, but the studies are quite complex to carry out,” noted Andrew Blagborough, PhD, of Imperial College London in the UK.

For this study, he and his colleagues set up repeated cycles of infection so that groups of infected mosquitoes containing variable numbers of parasites repeatedly bit sedated mice, transmitting malaria to them under a range of transmission settings.

This allowed the researchers to track how many individual parasites different mosquitoes harbored, how many mice were infected as a result of exposure to them, and how long it took the mice to develop malaria.

The team also analyzed data from human volunteers who were exposed to bites from infectious mosquitoes.

Dissection of these mosquitoes revealed that infection was significantly more likely—and occurred sooner—after bites from mosquitoes with more than 1000 individual parasites in their salivary glands.

By conducting further studies with mice and human volunteers, the researchers were able to provide an explanation for why the malaria vaccine RTS,S is effective only some of the time and why any protection rapidly drops off after 3 years.

The vaccine was less effective when mice or humans were bitten by mosquitoes carrying a greater number of parasites. The researchers think this is because the vaccine can only kill a certain proportion of the parasites and is overwhelmed when the parasite population is too large.

“Vaccine development has come a long way, and this new insight should help future vaccine studies to be tested more rigorously,” said study author Thomas Churcher, PhD, of Imperial College London.

“However, in the end, it is unlikely that one magic bullet will eradicate malaria, and we should continue to seek and apply combinations of strategies for reducing the burden of this disease.”

Malaria-carrying mosquito
Photo by James Gathany

Mosquitoes carrying a greater number of malaria-causing parasites may be more likely to cause infection, according to a study published in PLOS Pathogens.

More than 100 years have passed since scientists first discovered that infectious mosquitoes inject malaria parasites when they bite people.

However, it hasn’t been clear whether injecting more parasites with each bite increases a person’s chances of infection or if all infectious bites are equally dangerous.

In the new study, researchers set out to determine whether the number of parasites found in the salivary glands of malaria-carrying mosquitos impacts disease transmission.

Via experiments in mice, the team determined that the more parasites present in a mosquito’s salivary glands, the more likely it was to be infectious and the faster an infection would develop.

“It is surprising that the relationship between parasite density and infectiousness has not been properly investigated before, but the studies are quite complex to carry out,” noted Andrew Blagborough, PhD, of Imperial College London in the UK.

For this study, he and his colleagues set up repeated cycles of infection so that groups of infected mosquitoes containing variable numbers of parasites repeatedly bit sedated mice, transmitting malaria to them under a range of transmission settings.

This allowed the researchers to track how many individual parasites different mosquitoes harbored, how many mice were infected as a result of exposure to them, and how long it took the mice to develop malaria.

The team also analyzed data from human volunteers who were exposed to bites from infectious mosquitoes.

Dissection of these mosquitoes revealed that infection was significantly more likely—and occurred sooner—after bites from mosquitoes with more than 1000 individual parasites in their salivary glands.

By conducting further studies with mice and human volunteers, the researchers were able to provide an explanation for why the malaria vaccine RTS,S is effective only some of the time and why any protection rapidly drops off after 3 years.

The vaccine was less effective when mice or humans were bitten by mosquitoes carrying a greater number of parasites. The researchers think this is because the vaccine can only kill a certain proportion of the parasites and is overwhelmed when the parasite population is too large.

“Vaccine development has come a long way, and this new insight should help future vaccine studies to be tested more rigorously,” said study author Thomas Churcher, PhD, of Imperial College London.

“However, in the end, it is unlikely that one magic bullet will eradicate malaria, and we should continue to seek and apply combinations of strategies for reducing the burden of this disease.”

Woman wearing nebulizer mask
Photo by James Heilman

The US Food and Drug Administration (FDA) is warning consumers not to purchase or use PNC-27, a product being promoted and sold through PNC27.com as a treatment for all cancers.

The FDA has not evaluated or approved PNC-27 as safe and effective to treat any disease, including any form of cancer.

In addition, an FDA laboratory discovered the bacteria Variovorax paradoxus in a PNC-27 solution sample for inhalation.

The FDA has not received reports of illnesses or serious adverse events related to PNC-27.

However, the agency said consumers who use a contaminated product are at risk for serious, potentially life-threatening infections.

Individuals at higher risk include vulnerable populations, such as young children, elderly people, pregnant women, and individuals with weakened immune systems.

PNC-27 may be available in various dosage forms, such as a nebulized solution, intravenous solution, vaginal suppository, or rectal suppository.

The FDA recommends that patients who have used any PNC-27 product and have concerns contact their healthcare provider as soon as possible.

The agency is also encouraging healthcare professionals and consumers to report any adverse events possibly related to the use of a PNC-27 product to the FDA’s MedWatch Adverse Event Reporting Program.

Woman wearing nebulizer mask
Photo by James Heilman

The US Food and Drug Administration (FDA) is warning consumers not to purchase or use PNC-27, a product being promoted and sold through PNC27.com as a treatment for all cancers.

The FDA has not evaluated or approved PNC-27 as safe and effective to treat any disease, including any form of cancer.

In addition, an FDA laboratory discovered the bacteria Variovorax paradoxus in a PNC-27 solution sample for inhalation.

The FDA has not received reports of illnesses or serious adverse events related to PNC-27.

However, the agency said consumers who use a contaminated product are at risk for serious, potentially life-threatening infections.

Individuals at higher risk include vulnerable populations, such as young children, elderly people, pregnant women, and individuals with weakened immune systems.

PNC-27 may be available in various dosage forms, such as a nebulized solution, intravenous solution, vaginal suppository, or rectal suppository.

The FDA recommends that patients who have used any PNC-27 product and have concerns contact their healthcare provider as soon as possible.

The agency is also encouraging healthcare professionals and consumers to report any adverse events possibly related to the use of a PNC-27 product to the FDA’s MedWatch Adverse Event Reporting Program.

Woman wearing nebulizer mask
Photo by James Heilman

The US Food and Drug Administration (FDA) is warning consumers not to purchase or use PNC-27, a product being promoted and sold through PNC27.com as a treatment for all cancers.

The FDA has not evaluated or approved PNC-27 as safe and effective to treat any disease, including any form of cancer.

In addition, an FDA laboratory discovered the bacteria Variovorax paradoxus in a PNC-27 solution sample for inhalation.

The FDA has not received reports of illnesses or serious adverse events related to PNC-27.

However, the agency said consumers who use a contaminated product are at risk for serious, potentially life-threatening infections.

Individuals at higher risk include vulnerable populations, such as young children, elderly people, pregnant women, and individuals with weakened immune systems.

PNC-27 may be available in various dosage forms, such as a nebulized solution, intravenous solution, vaginal suppository, or rectal suppository.

The FDA recommends that patients who have used any PNC-27 product and have concerns contact their healthcare provider as soon as possible.

The agency is also encouraging healthcare professionals and consumers to report any adverse events possibly related to the use of a PNC-27 product to the FDA’s MedWatch Adverse Event Reporting Program.

Blood in bags and vials
Photo by Daniel Gay

Abbott’s Alinity s System for blood and plasma screening has received the CE mark and is now available for use in countries that recognize the mark.

The Alinity s System is designed to screen blood and plasma faster and more efficiently than Abbott’s current systems.

The company said the additional automation and flexibility of the Alinity s System helps blood and plasma centers improve productivity and maintain accuracy without expanding the instrument footprint.

According to Abbott, the Alinity s System offers a number of new features. It expands capacity to run up to 600 tests per hour, and it increases walk-away time to a minimum of 3 hours.

The system also gives laboratory professionals the ability to continuously load and

unload samples and supplies without pausing or stopping the system.

The Alinity s System improves centers’ ability to track all activities and actions associated with the testing and processing of each donation in accordance with relevant legislation and requirements.

And the system features an intuitive software interface, menu design, and sample loading layout (shared with other Alinity instruments), making it easy for lab technicians to learn and use.

“When Abbott developed the Alinity s System, we considered the challenges that blood and plasma centers face today as well as in the future, such as adequate space, easier training, and more time for lab professionals to work away from the instrument,” said Daman Kowalski, divisional vice president of new product development in diagnostics at Abbott.

“In addressing these challenges, the Alinity s System has the potential to transform how quickly and accurately these centers can screen blood and plasma, which means we can deliver life-saving blood components to the people who need it the most.”

Blood in bags and vials
Photo by Daniel Gay

Abbott’s Alinity s System for blood and plasma screening has received the CE mark and is now available for use in countries that recognize the mark.

The Alinity s System is designed to screen blood and plasma faster and more efficiently than Abbott’s current systems.

The company said the additional automation and flexibility of the Alinity s System helps blood and plasma centers improve productivity and maintain accuracy without expanding the instrument footprint.

According to Abbott, the Alinity s System offers a number of new features. It expands capacity to run up to 600 tests per hour, and it increases walk-away time to a minimum of 3 hours.

The system also gives laboratory professionals the ability to continuously load and

unload samples and supplies without pausing or stopping the system.

The Alinity s System improves centers’ ability to track all activities and actions associated with the testing and processing of each donation in accordance with relevant legislation and requirements.

And the system features an intuitive software interface, menu design, and sample loading layout (shared with other Alinity instruments), making it easy for lab technicians to learn and use.

“When Abbott developed the Alinity s System, we considered the challenges that blood and plasma centers face today as well as in the future, such as adequate space, easier training, and more time for lab professionals to work away from the instrument,” said Daman Kowalski, divisional vice president of new product development in diagnostics at Abbott.

“In addressing these challenges, the Alinity s System has the potential to transform how quickly and accurately these centers can screen blood and plasma, which means we can deliver life-saving blood components to the people who need it the most.”

Blood in bags and vials
Photo by Daniel Gay

Abbott’s Alinity s System for blood and plasma screening has received the CE mark and is now available for use in countries that recognize the mark.

The Alinity s System is designed to screen blood and plasma faster and more efficiently than Abbott’s current systems.

The company said the additional automation and flexibility of the Alinity s System helps blood and plasma centers improve productivity and maintain accuracy without expanding the instrument footprint.

According to Abbott, the Alinity s System offers a number of new features. It expands capacity to run up to 600 tests per hour, and it increases walk-away time to a minimum of 3 hours.

The system also gives laboratory professionals the ability to continuously load and

unload samples and supplies without pausing or stopping the system.

The Alinity s System improves centers’ ability to track all activities and actions associated with the testing and processing of each donation in accordance with relevant legislation and requirements.

And the system features an intuitive software interface, menu design, and sample loading layout (shared with other Alinity instruments), making it easy for lab technicians to learn and use.

“When Abbott developed the Alinity s System, we considered the challenges that blood and plasma centers face today as well as in the future, such as adequate space, easier training, and more time for lab professionals to work away from the instrument,” said Daman Kowalski, divisional vice president of new product development in diagnostics at Abbott.

“In addressing these challenges, the Alinity s System has the potential to transform how quickly and accurately these centers can screen blood and plasma, which means we can deliver life-saving blood components to the people who need it the most.”

CVS Pharmacy is currently selling a generic epinephrine autoinjector for a price of $109.99 per two-pack, which is about one-sixth the cost of Mylan’s EpiPen two-pack.

The product, an authorized generic for Adrenaclick, is manufactured by Lineage Therapeutics, which is a wholly owned subsidiary of Fort Washington, Pa.–based Impax Laboratories. CVS Pharmacy characterized the product as having “the lowest cash price in the market” and said in a Jan. 12 statement that the move was undertaken to address the “urgent need for a less-expensive epinephrine autoinjector.”
 

Data from a Kaiser Family Foundation analysis found that the average total Part D Medicare spending per EpiPen prescription increased nearly fivefold, from an average of $71 in 2007 to $344 in 2014. This trend continued, and in September 2016, Mylan’s CEO Heather Bresch faced questioning on Capitol Hill about the price hikes from members of the House Oversight Committee.

“We’re encouraged to see national efforts to make epinephrine autoinjectors more affordable and more available to Americans across the country,” Cary Sennett, MD, PhD, president and CEO of the Landover, Md.–based Asthma and Allergy Foundation of America, said in the CVS statement. “Partnerships that increase access to vital medications are key in helping those suffering from life-threatening allergies.”
 

dbrunk@frontlinemedcom.com

CVS Pharmacy is currently selling a generic epinephrine autoinjector for a price of $109.99 per two-pack, which is about one-sixth the cost of Mylan’s EpiPen two-pack.

The product, an authorized generic for Adrenaclick, is manufactured by Lineage Therapeutics, which is a wholly owned subsidiary of Fort Washington, Pa.–based Impax Laboratories. CVS Pharmacy characterized the product as having “the lowest cash price in the market” and said in a Jan. 12 statement that the move was undertaken to address the “urgent need for a less-expensive epinephrine autoinjector.”
 

Data from a Kaiser Family Foundation analysis found that the average total Part D Medicare spending per EpiPen prescription increased nearly fivefold, from an average of $71 in 2007 to $344 in 2014. This trend continued, and in September 2016, Mylan’s CEO Heather Bresch faced questioning on Capitol Hill about the price hikes from members of the House Oversight Committee.

“We’re encouraged to see national efforts to make epinephrine autoinjectors more affordable and more available to Americans across the country,” Cary Sennett, MD, PhD, president and CEO of the Landover, Md.–based Asthma and Allergy Foundation of America, said in the CVS statement. “Partnerships that increase access to vital medications are key in helping those suffering from life-threatening allergies.”
 

dbrunk@frontlinemedcom.com

CVS Pharmacy is currently selling a generic epinephrine autoinjector for a price of $109.99 per two-pack, which is about one-sixth the cost of Mylan’s EpiPen two-pack.

The product, an authorized generic for Adrenaclick, is manufactured by Lineage Therapeutics, which is a wholly owned subsidiary of Fort Washington, Pa.–based Impax Laboratories. CVS Pharmacy characterized the product as having “the lowest cash price in the market” and said in a Jan. 12 statement that the move was undertaken to address the “urgent need for a less-expensive epinephrine autoinjector.”
 

Data from a Kaiser Family Foundation analysis found that the average total Part D Medicare spending per EpiPen prescription increased nearly fivefold, from an average of $71 in 2007 to $344 in 2014. This trend continued, and in September 2016, Mylan’s CEO Heather Bresch faced questioning on Capitol Hill about the price hikes from members of the House Oversight Committee.

“We’re encouraged to see national efforts to make epinephrine autoinjectors more affordable and more available to Americans across the country,” Cary Sennett, MD, PhD, president and CEO of the Landover, Md.–based Asthma and Allergy Foundation of America, said in the CVS statement. “Partnerships that increase access to vital medications are key in helping those suffering from life-threatening allergies.”
 

dbrunk@frontlinemedcom.com

Adult patients who experience stress in the form of “anxiety sensitivity” are more likely to develop psychodermatological conditions than those that are not psychodermatological, a cross-sectional study of 115 participants shows.

“The results suggest that [anxiety sensitivity] interventions combined with dermatology treatments may be beneficial for psychodermatological patients,” wrote Laura J. Dixon, PhD, of the University of Mississippi Medical Center, Jackson, and her associates. “There is strong evidence that cognitive-behavioral therapy significantly reduces [anxiety sensitivity] through strategies such as psychoeducation, interoceptive exposure, and cognitive therapy.”

Dr. Dixon and her associates recruited 123 dermatologic patients aged 18-83 years over 30 weeks through three outpatient university dermatology clinics in Central Mississippi. Sixty-five percent of the participants were white, 33% were black, 1% were Asian, and 1% were Native American; 65% were female. Most of the patients were married and living with their spouses. The final sample of participants comprised 63 psychodermatological patients and 52 nonpsychodermatological patients (Psychosomatics. 2016;57:498-504).

The investigators assessed general anxiety symptoms using the 7-item depression, anxiety, and stress subscale (DASS-A) from the 21-item version of the questionnaire (DASS-21). Anxiety sensitivity – which refers to the “extent of beliefs that anxiety symptoms or arousal can have harmful consequences” (Turk Psikiyatri Derg. 2011 Fall;22[3]:187-93) – was measured using the Anxiety Sensitivity Index–3 (ASI-3, an 18-item self-report instrument that assesses physical manifestations of anxiety, such as blushing and fast heart beating.

Psychodermatological conditions were classified as disorders that might be rooted in or made worse by psychological, behavioral, or stress-related factors. Conditions in this category include acne, alopecia, atopic dermatitis, eczema, hidradenitis, prurigo, psoriasis, and rosacea. Dermatologic conditions not tied to psychological factors and classified as biologically based include brittle fingernails, cysts, keloids, rashes, skin cancer, skin lesions, spider veins, and warts, reported Dr. Dixon.

No significant differences were observed on the DASS-A scores between the two groups.

The mean scores of psychodermatological patients on the ASI-3 were significantly higher than the scores of patients with nonpsychodermatological conditions (21.1 vs. 13.7; P = .013). In fact, Dr. Dixon and her associates found that “each 1-unit increment in the ASI-3 social subscale score was associated with a 12.7% increased odds of patients having a psychodermatological condition.”

“Taken together, these results are supported by existing theoretical models of psychodermatological disorders that highlight the importance of stress among patients with certain dermatological conditions,” the researchers wrote.

One of the authors, dermatologist Robert T. Brodell, disclosed receiving honoraria from Allergan, Galderma Laboratories, and PharmaDerm; he also disclosed receiving consultant fees and performing clinical trials for other pharmaceutical companies. Neither Dr. Dixon nor any of the other authors declared relevant financial disclosures.

ghenderson@frontlinemedcom.com

On Twitter @ginalhenderson

Adult patients who experience stress in the form of “anxiety sensitivity” are more likely to develop psychodermatological conditions than those that are not psychodermatological, a cross-sectional study of 115 participants shows.

“The results suggest that [anxiety sensitivity] interventions combined with dermatology treatments may be beneficial for psychodermatological patients,” wrote Laura J. Dixon, PhD, of the University of Mississippi Medical Center, Jackson, and her associates. “There is strong evidence that cognitive-behavioral therapy significantly reduces [anxiety sensitivity] through strategies such as psychoeducation, interoceptive exposure, and cognitive therapy.”

Dr. Dixon and her associates recruited 123 dermatologic patients aged 18-83 years over 30 weeks through three outpatient university dermatology clinics in Central Mississippi. Sixty-five percent of the participants were white, 33% were black, 1% were Asian, and 1% were Native American; 65% were female. Most of the patients were married and living with their spouses. The final sample of participants comprised 63 psychodermatological patients and 52 nonpsychodermatological patients (Psychosomatics. 2016;57:498-504).

The investigators assessed general anxiety symptoms using the 7-item depression, anxiety, and stress subscale (DASS-A) from the 21-item version of the questionnaire (DASS-21). Anxiety sensitivity – which refers to the “extent of beliefs that anxiety symptoms or arousal can have harmful consequences” (Turk Psikiyatri Derg. 2011 Fall;22[3]:187-93) – was measured using the Anxiety Sensitivity Index–3 (ASI-3, an 18-item self-report instrument that assesses physical manifestations of anxiety, such as blushing and fast heart beating.

Psychodermatological conditions were classified as disorders that might be rooted in or made worse by psychological, behavioral, or stress-related factors. Conditions in this category include acne, alopecia, atopic dermatitis, eczema, hidradenitis, prurigo, psoriasis, and rosacea. Dermatologic conditions not tied to psychological factors and classified as biologically based include brittle fingernails, cysts, keloids, rashes, skin cancer, skin lesions, spider veins, and warts, reported Dr. Dixon.

No significant differences were observed on the DASS-A scores between the two groups.

The mean scores of psychodermatological patients on the ASI-3 were significantly higher than the scores of patients with nonpsychodermatological conditions (21.1 vs. 13.7; P = .013). In fact, Dr. Dixon and her associates found that “each 1-unit increment in the ASI-3 social subscale score was associated with a 12.7% increased odds of patients having a psychodermatological condition.”

“Taken together, these results are supported by existing theoretical models of psychodermatological disorders that highlight the importance of stress among patients with certain dermatological conditions,” the researchers wrote.

One of the authors, dermatologist Robert T. Brodell, disclosed receiving honoraria from Allergan, Galderma Laboratories, and PharmaDerm; he also disclosed receiving consultant fees and performing clinical trials for other pharmaceutical companies. Neither Dr. Dixon nor any of the other authors declared relevant financial disclosures.

ghenderson@frontlinemedcom.com

On Twitter @ginalhenderson

Adult patients who experience stress in the form of “anxiety sensitivity” are more likely to develop psychodermatological conditions than those that are not psychodermatological, a cross-sectional study of 115 participants shows.

“The results suggest that [anxiety sensitivity] interventions combined with dermatology treatments may be beneficial for psychodermatological patients,” wrote Laura J. Dixon, PhD, of the University of Mississippi Medical Center, Jackson, and her associates. “There is strong evidence that cognitive-behavioral therapy significantly reduces [anxiety sensitivity] through strategies such as psychoeducation, interoceptive exposure, and cognitive therapy.”

Dr. Dixon and her associates recruited 123 dermatologic patients aged 18-83 years over 30 weeks through three outpatient university dermatology clinics in Central Mississippi. Sixty-five percent of the participants were white, 33% were black, 1% were Asian, and 1% were Native American; 65% were female. Most of the patients were married and living with their spouses. The final sample of participants comprised 63 psychodermatological patients and 52 nonpsychodermatological patients (Psychosomatics. 2016;57:498-504).

The investigators assessed general anxiety symptoms using the 7-item depression, anxiety, and stress subscale (DASS-A) from the 21-item version of the questionnaire (DASS-21). Anxiety sensitivity – which refers to the “extent of beliefs that anxiety symptoms or arousal can have harmful consequences” (Turk Psikiyatri Derg. 2011 Fall;22[3]:187-93) – was measured using the Anxiety Sensitivity Index–3 (ASI-3, an 18-item self-report instrument that assesses physical manifestations of anxiety, such as blushing and fast heart beating.

Psychodermatological conditions were classified as disorders that might be rooted in or made worse by psychological, behavioral, or stress-related factors. Conditions in this category include acne, alopecia, atopic dermatitis, eczema, hidradenitis, prurigo, psoriasis, and rosacea. Dermatologic conditions not tied to psychological factors and classified as biologically based include brittle fingernails, cysts, keloids, rashes, skin cancer, skin lesions, spider veins, and warts, reported Dr. Dixon.

No significant differences were observed on the DASS-A scores between the two groups.

The mean scores of psychodermatological patients on the ASI-3 were significantly higher than the scores of patients with nonpsychodermatological conditions (21.1 vs. 13.7; P = .013). In fact, Dr. Dixon and her associates found that “each 1-unit increment in the ASI-3 social subscale score was associated with a 12.7% increased odds of patients having a psychodermatological condition.”

“Taken together, these results are supported by existing theoretical models of psychodermatological disorders that highlight the importance of stress among patients with certain dermatological conditions,” the researchers wrote.

One of the authors, dermatologist Robert T. Brodell, disclosed receiving honoraria from Allergan, Galderma Laboratories, and PharmaDerm; he also disclosed receiving consultant fees and performing clinical trials for other pharmaceutical companies. Neither Dr. Dixon nor any of the other authors declared relevant financial disclosures.

ghenderson@frontlinemedcom.com

On Twitter @ginalhenderson

Just over 55% of adult cigarette smokers made an attempt to quit in the past year, and 7.4% said that they recently quit, according to investigators from the Centers or Disease Control and Prevention.

Data from the 2015 National Health Interview Survey (NHIS) show that 68% of cigarette smokers were interested in quitting, with considerable variation seen according to race and ethnicity (MMWR. 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

Just over 55% of adult cigarette smokers made an attempt to quit in the past year, and 7.4% said that they recently quit, according to investigators from the Centers or Disease Control and Prevention.

Data from the 2015 National Health Interview Survey (NHIS) show that 68% of cigarette smokers were interested in quitting, with considerable variation seen according to race and ethnicity (MMWR. 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

Just over 55% of adult cigarette smokers made an attempt to quit in the past year, and 7.4% said that they recently quit, according to investigators from the Centers or Disease Control and Prevention.

Data from the 2015 National Health Interview Survey (NHIS) show that 68% of cigarette smokers were interested in quitting, with considerable variation seen according to race and ethnicity (MMWR. 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

More than half of cigarette smokers have received advice to quit from a health care professional, but less than a third used medication or counseling in their cessation attempt, according to investigators from the Centers for Disease Control and Prevention.

In 2015, just over 57% of adult smokers said that a health care professional had advised them to quit in the past year. Of those who tried to quit, 29% used medication such as nicotine patches or gum, varenicline, or bupropion; 7% used counseling (including a stop-smoking clinic, class, or support group and a telephone help line); and 31% used counseling and/or medication, the investigators reported (MMWR 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

More than half of cigarette smokers have received advice to quit from a health care professional, but less than a third used medication or counseling in their cessation attempt, according to investigators from the Centers for Disease Control and Prevention.

In 2015, just over 57% of adult smokers said that a health care professional had advised them to quit in the past year. Of those who tried to quit, 29% used medication such as nicotine patches or gum, varenicline, or bupropion; 7% used counseling (including a stop-smoking clinic, class, or support group and a telephone help line); and 31% used counseling and/or medication, the investigators reported (MMWR 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

More than half of cigarette smokers have received advice to quit from a health care professional, but less than a third used medication or counseling in their cessation attempt, according to investigators from the Centers for Disease Control and Prevention.

In 2015, just over 57% of adult smokers said that a health care professional had advised them to quit in the past year. Of those who tried to quit, 29% used medication such as nicotine patches or gum, varenicline, or bupropion; 7% used counseling (including a stop-smoking clinic, class, or support group and a telephone help line); and 31% used counseling and/or medication, the investigators reported (MMWR 2017;65[52]:1457-64).

rfranki@frontlinemedcom.com

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

sworcester@frontlinemedcom.com

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

sworcester@frontlinemedcom.com

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

sworcester@frontlinemedcom.com

With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act. The House of Representatives passed similar legislation Jan. 13.*

Republicans will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage in the Senate.

The budget resolutions contain no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

*This story was updated Jan. 13 at 4:30 pm.

gtwachtman@frontlinemedcom.com

With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act. The House of Representatives passed similar legislation Jan. 13.*

Republicans will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage in the Senate.

The budget resolutions contain no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

*This story was updated Jan. 13 at 4:30 pm.

gtwachtman@frontlinemedcom.com

With a Jan. 12 early morning procedural passed on party lines, the Senate has set the stage for the repeal of the revenue aspects of the Affordable Care Act. The House of Representatives passed similar legislation Jan. 13.*

Republicans will be using the budget reconciliation process, which will allow them to move forward with repealing certain provisions of the health care reform law without any Democratic support, although passage of any replacement will require some bipartisan support as Republicans do not have the required 60 votes to guarantee passage in the Senate.

The budget resolutions contain no details about what could be repealed or whether there will be a replacement, but it does direct the key committees to write draft legislation by Jan. 27.

*This story was updated Jan. 13 at 4:30 pm.

gtwachtman@frontlinemedcom.com