Hematology Times

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the recombinant antihemophilic factor Kovaltry for the treatment of adults and children with hemophilia A.

Kovaltry is an unmodified, full-length factor VIII compound indicated for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

Dosing of Kovaltry should be individualized based on each patient’s clinical response.

The recommended dosing for adults and adolescents is 20 to 40 IU per kg of body weight 2 or 3 times per week. The recommended dosing for children age 12 and younger is 25 to 50 IU per kg of body weight twice weekly, 3 times weekly, or every other day, according to individual requirements.

For more details, see the full prescribing information.

The FDA’s approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A. The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the recombinant antihemophilic factor Kovaltry for the treatment of adults and children with hemophilia A.

Kovaltry is an unmodified, full-length factor VIII compound indicated for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

Dosing of Kovaltry should be individualized based on each patient’s clinical response.

The recommended dosing for adults and adolescents is 20 to 40 IU per kg of body weight 2 or 3 times per week. The recommended dosing for children age 12 and younger is 25 to 50 IU per kg of body weight twice weekly, 3 times weekly, or every other day, according to individual requirements.

For more details, see the full prescribing information.

The FDA’s approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A. The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Vials of drug

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the recombinant antihemophilic factor Kovaltry for the treatment of adults and children with hemophilia A.

Kovaltry is an unmodified, full-length factor VIII compound indicated for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

Dosing of Kovaltry should be individualized based on each patient’s clinical response.

The recommended dosing for adults and adolescents is 20 to 40 IU per kg of body weight 2 or 3 times per week. The recommended dosing for children age 12 and younger is 25 to 50 IU per kg of body weight twice weekly, 3 times weekly, or every other day, according to individual requirements.

For more details, see the full prescribing information.

The FDA’s approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A. The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Lab mouse

Preclinical research indicates that a novel inhibitor can overcome resistance-conferring FLT3 mutations in acute myeloid leukemia (AML).

The MERTK/FLT3 inhibitor MRX-2843 induced apoptosis and inhibited colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD.

MRX-2843 also improved survival in mouse models of AML, including cases where tumors were resistant to the FLT3 inhibitor quizartinib.

Douglas Graham, MD, PhD, of the University of Colorado in Aurora, and his colleagues conducted this research and reported the results in JCI Insight.

The researchers previously showed that the receptor tyrosine kinase MERTK is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis.

With the current study, they showed that MRX-2843 abrogates activation of MERTK, FLT3, and their downstream effectors. And this translates to antileukemic activity in vitro and in vivo.

MRX-2843 inhibited MERTK signaling, induced cell death, and abolished oncogenic phenotypes in AML cells. The drug also exhibited therapeutic activity in a MERTK-dependent xenograft model.

MRX-2843 was able to stop the activation of FLT3 and its signaling pathways almost completely. The researchers said this suggests the drug has somewhat higher cellular potency against FLT3 relative to MERTK.

In mouse models of FLT3-ITD AML, MRX-2843 significantly prolonged survival when compared to vehicle control.

The researchers also said MRX-2843 selectively inhibited colony formation in primary AML patient samples. Primary human MERTK-expressing leukemic blasts, with or without FLT3-ITD mutations, proved sensitive to treatment with MRX-2843.

In addition, MRX-2843 increased survival and decreased peripheral disease burden in patient-derived xenograft models of AML—both MERTK⁺FLT3-WT and MERTK⁺FLT3-ITD models.

Finally, the researchers found that MRX-2843 was active against quizartinib-resistant FLT3-mutant proteins, induced apoptosis and inhibited colony formation in quizartinib-resistant FLT3-ITD cell lines, and prolonged survival in quizartinib-resistant FLT3-ITD xenograft models.

Lab mouse

Preclinical research indicates that a novel inhibitor can overcome resistance-conferring FLT3 mutations in acute myeloid leukemia (AML).

The MERTK/FLT3 inhibitor MRX-2843 induced apoptosis and inhibited colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD.

MRX-2843 also improved survival in mouse models of AML, including cases where tumors were resistant to the FLT3 inhibitor quizartinib.

Douglas Graham, MD, PhD, of the University of Colorado in Aurora, and his colleagues conducted this research and reported the results in JCI Insight.

The researchers previously showed that the receptor tyrosine kinase MERTK is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis.

With the current study, they showed that MRX-2843 abrogates activation of MERTK, FLT3, and their downstream effectors. And this translates to antileukemic activity in vitro and in vivo.

MRX-2843 inhibited MERTK signaling, induced cell death, and abolished oncogenic phenotypes in AML cells. The drug also exhibited therapeutic activity in a MERTK-dependent xenograft model.

MRX-2843 was able to stop the activation of FLT3 and its signaling pathways almost completely. The researchers said this suggests the drug has somewhat higher cellular potency against FLT3 relative to MERTK.

In mouse models of FLT3-ITD AML, MRX-2843 significantly prolonged survival when compared to vehicle control.

The researchers also said MRX-2843 selectively inhibited colony formation in primary AML patient samples. Primary human MERTK-expressing leukemic blasts, with or without FLT3-ITD mutations, proved sensitive to treatment with MRX-2843.

In addition, MRX-2843 increased survival and decreased peripheral disease burden in patient-derived xenograft models of AML—both MERTK⁺FLT3-WT and MERTK⁺FLT3-ITD models.

Finally, the researchers found that MRX-2843 was active against quizartinib-resistant FLT3-mutant proteins, induced apoptosis and inhibited colony formation in quizartinib-resistant FLT3-ITD cell lines, and prolonged survival in quizartinib-resistant FLT3-ITD xenograft models.

Lab mouse

Preclinical research indicates that a novel inhibitor can overcome resistance-conferring FLT3 mutations in acute myeloid leukemia (AML).

The MERTK/FLT3 inhibitor MRX-2843 induced apoptosis and inhibited colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD.

MRX-2843 also improved survival in mouse models of AML, including cases where tumors were resistant to the FLT3 inhibitor quizartinib.

Douglas Graham, MD, PhD, of the University of Colorado in Aurora, and his colleagues conducted this research and reported the results in JCI Insight.

The researchers previously showed that the receptor tyrosine kinase MERTK is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis.

With the current study, they showed that MRX-2843 abrogates activation of MERTK, FLT3, and their downstream effectors. And this translates to antileukemic activity in vitro and in vivo.

MRX-2843 inhibited MERTK signaling, induced cell death, and abolished oncogenic phenotypes in AML cells. The drug also exhibited therapeutic activity in a MERTK-dependent xenograft model.

MRX-2843 was able to stop the activation of FLT3 and its signaling pathways almost completely. The researchers said this suggests the drug has somewhat higher cellular potency against FLT3 relative to MERTK.

In mouse models of FLT3-ITD AML, MRX-2843 significantly prolonged survival when compared to vehicle control.

The researchers also said MRX-2843 selectively inhibited colony formation in primary AML patient samples. Primary human MERTK-expressing leukemic blasts, with or without FLT3-ITD mutations, proved sensitive to treatment with MRX-2843.

In addition, MRX-2843 increased survival and decreased peripheral disease burden in patient-derived xenograft models of AML—both MERTK⁺FLT3-WT and MERTK⁺FLT3-ITD models.

Finally, the researchers found that MRX-2843 was active against quizartinib-resistant FLT3-mutant proteins, induced apoptosis and inhibited colony formation in quizartinib-resistant FLT3-ITD cell lines, and prolonged survival in quizartinib-resistant FLT3-ITD xenograft models.

Ondansetron

Researchers say they have discovered the source of a bloodstream infection observed in more than 50 South American cancer patients.

Using whole-genome sequence typing (WGST), the team was able to link infection with the fungus Sarocladium kiliense to a tainted antinausea medication, ondansetron, that was given to cancer patients in Chile and Colombia.

This work is described in Emerging Infectious Diseases.

“Contamination of medical products, particularly with environmental fungi, poses growing concern and a public health threat, especially in vulnerable populations such as cancer patients,” said study author David Engelthaler, PhD, of The Translational Genomics Research Institute in Flagstaff, Arizona.

“Increased vigilance and the use of advanced technologies are needed to rapidly identify the likely sources of infection to efficiently guide epidemiologic investigations and initiate appropriate control measures.”

The S kiliense bloodstream-infection outbreak, which occurred from June 2013 through January 2014, included a cluster of cases at 8 hospitals in Santiago, Chile.

All of the patients received the same 4 intravenous medications. But only the antinausea medication ondansetron was given exclusively to cancer patients.

All of the patients infected with S kiliense received ondansetron from the same source, a pharmaceutical company called Vitrofarma SA (specifically, Plant No. 8 in Bogotá, Colombia). The drug was imported by LabVitales Chile SA and distributed by Pharma Isa Ltda.

Two of 3 lots of unopened ondansetron, tested by the Chilean Ministry of Health, yielded vials contaminated with S kiliense, forcing a recall of all ondansetron in Chile that was made by Vitrofarma SA.

Subsequently, Colombian officials discovered 14 other cases in which patients who were given ondansetron from Vitrofarma SA were infected with S kiliense.

S kiliense has been implicated in healthcare-related infections before, but the lack of available typing methods has precluded the ability to substantiate sources.

“The use of WGST to investigate fungal outbreaks has become integral to epidemiologic investigations,” Dr Engelthaler said. “Our WGST analysis demonstrated that the patient isolates from Chile and Colombia were nearly genetically indistinguishable from those recovered from the unopened medication vials, indicating the likely presence of a single-source infection.”

Ondansetron

Researchers say they have discovered the source of a bloodstream infection observed in more than 50 South American cancer patients.

Using whole-genome sequence typing (WGST), the team was able to link infection with the fungus Sarocladium kiliense to a tainted antinausea medication, ondansetron, that was given to cancer patients in Chile and Colombia.

This work is described in Emerging Infectious Diseases.

“Contamination of medical products, particularly with environmental fungi, poses growing concern and a public health threat, especially in vulnerable populations such as cancer patients,” said study author David Engelthaler, PhD, of The Translational Genomics Research Institute in Flagstaff, Arizona.

“Increased vigilance and the use of advanced technologies are needed to rapidly identify the likely sources of infection to efficiently guide epidemiologic investigations and initiate appropriate control measures.”

The S kiliense bloodstream-infection outbreak, which occurred from June 2013 through January 2014, included a cluster of cases at 8 hospitals in Santiago, Chile.

All of the patients received the same 4 intravenous medications. But only the antinausea medication ondansetron was given exclusively to cancer patients.

All of the patients infected with S kiliense received ondansetron from the same source, a pharmaceutical company called Vitrofarma SA (specifically, Plant No. 8 in Bogotá, Colombia). The drug was imported by LabVitales Chile SA and distributed by Pharma Isa Ltda.

Two of 3 lots of unopened ondansetron, tested by the Chilean Ministry of Health, yielded vials contaminated with S kiliense, forcing a recall of all ondansetron in Chile that was made by Vitrofarma SA.

Subsequently, Colombian officials discovered 14 other cases in which patients who were given ondansetron from Vitrofarma SA were infected with S kiliense.

S kiliense has been implicated in healthcare-related infections before, but the lack of available typing methods has precluded the ability to substantiate sources.

“The use of WGST to investigate fungal outbreaks has become integral to epidemiologic investigations,” Dr Engelthaler said. “Our WGST analysis demonstrated that the patient isolates from Chile and Colombia were nearly genetically indistinguishable from those recovered from the unopened medication vials, indicating the likely presence of a single-source infection.”

Ondansetron

Researchers say they have discovered the source of a bloodstream infection observed in more than 50 South American cancer patients.

Using whole-genome sequence typing (WGST), the team was able to link infection with the fungus Sarocladium kiliense to a tainted antinausea medication, ondansetron, that was given to cancer patients in Chile and Colombia.

This work is described in Emerging Infectious Diseases.

“Contamination of medical products, particularly with environmental fungi, poses growing concern and a public health threat, especially in vulnerable populations such as cancer patients,” said study author David Engelthaler, PhD, of The Translational Genomics Research Institute in Flagstaff, Arizona.

“Increased vigilance and the use of advanced technologies are needed to rapidly identify the likely sources of infection to efficiently guide epidemiologic investigations and initiate appropriate control measures.”

The S kiliense bloodstream-infection outbreak, which occurred from June 2013 through January 2014, included a cluster of cases at 8 hospitals in Santiago, Chile.

All of the patients received the same 4 intravenous medications. But only the antinausea medication ondansetron was given exclusively to cancer patients.

All of the patients infected with S kiliense received ondansetron from the same source, a pharmaceutical company called Vitrofarma SA (specifically, Plant No. 8 in Bogotá, Colombia). The drug was imported by LabVitales Chile SA and distributed by Pharma Isa Ltda.

Two of 3 lots of unopened ondansetron, tested by the Chilean Ministry of Health, yielded vials contaminated with S kiliense, forcing a recall of all ondansetron in Chile that was made by Vitrofarma SA.

Subsequently, Colombian officials discovered 14 other cases in which patients who were given ondansetron from Vitrofarma SA were infected with S kiliense.

S kiliense has been implicated in healthcare-related infections before, but the lack of available typing methods has precluded the ability to substantiate sources.

“The use of WGST to investigate fungal outbreaks has become integral to epidemiologic investigations,” Dr Engelthaler said. “Our WGST analysis demonstrated that the patient isolates from Chile and Colombia were nearly genetically indistinguishable from those recovered from the unopened medication vials, indicating the likely presence of a single-source infection.”

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Antihemophilic factor

A large study suggests that, despite treatment advances, men with severe hemophilia have not seen great reductions in bleeding events.

Data on more than 7000 men with hemophilia revealed substantial differences in the care received by men born before 1958 and those born between 1983

and 1992.

However, the data also showed that frequent bleeding was common in patients with severe hemophilia, regardless of when they were born.

These data were published in Blood.

“Our analysis provides a snapshot of how improvements in care have translated into outcomes across different generations of men with hemophilia,” said study author Paul E. Monahan, MD, of The University of North Carolina-Chapel Hill.

“While there is reason to be pleased with the progress we’ve made, our data show some surprising deficits and suggest that efforts are needed to more consistently apply the integration of standard-of-care multidisciplinary services and preventive blood clotting factor treatments to further normalize the lives of men living with hemophilia.”

Dr Monahan and his colleagues analyzed data on 7486 men—4899 with severe hemophilia (65.4%), 2587 with mild hemophilia (34.6%), 6094 with hemophilia A (81.4%), and 1392 with hemophilia B (18.6%).

The data were collected prospectively by the US Centers for Disease Control and Prevention and 130 federally supported Hemophilia Treatment Centers (HTCs) between 1998 and 2011. This represents the largest database of men living with hemophilia.

The researchers grouped the men into 4 eras (birth cohorts) to evaluate how outcomes—access to care, physical and social functioning, complications, and mortality—have changed over the last 50 years.

The cohorts were as follows:

• Era A: born before 1958 (median age 58)
• Era B: born between 1958 and 1975 (median age 40)
• Era C: born between 1976 and 1982 (median age 28)
• Era D: born between 1983 and 1992 (median age 21).

Access to care

The researchers found that the proportion of men who started home infusions before age 6 was far greater in Era D than Era A—50.4% and 2%, respectively. And the proportion of patients reporting a first HTC visit before age 2 rose nearly 10-fold from Era A to Era D—8.8% and 100%, respectively.

In addition, the use of a continuous prophylactic regimen was nearly 3-fold greater in Era D than Era A—46.7% and 16%, respectively.

However, patients in the youngest 2 birth cohorts were more likely than their older counterparts to be uninsured. The proportion of uninsured patients was 16.4% in Era D, 20.5% in Era C, 11.1% in Era B, and 5.7% in Era A.

Bleeding events

The proportion of patients reporting frequent bleeds decreased from Era A to Era D. However, frequent bleeding was common in men with severe hemophilia regardless of when they were born.

Even men from Era D—who had access to effective, safe clotting therapies and multidisciplinary care throughout their lifetimes—reported frequent bleeds.

The proportion of patients with severe hemophilia reporting 5 or more joint bleeds in the last 6 months was 42.6% in Era A and 35.5% in Era D. The proportion of patients with a joint affected by recurrent bleeding was 32.6% and 24.9%, respectively.

Functioning

The researchers also discovered that patients with severe hemophilia were 3 times as likely to report limitations in their activities or to be disabled, when compared to patients with mild hemophilia, regardless of when they were born.

Still, men from Era A were more likely to report limitations in their overall activity level—68.8% of severe hemophilia patients and 21.1% of mild hemophilia patients—than men from Era D—14.9% of severe hemophilia patients and 4.3% of mild hemophilia patients.

Men with severe hemophilia were more likely than men with mild hemophilia to report missing more than 10 days of work or school during the previous year. In Era A, the proportions were 6.9% and 2.6%, respectively. In Era D, the proportions were 5.6% and 3%, respectively.

“Clear disparities remain in terms of frequent bleeding and disability between men with severe hemophilia and mild hemophilia across every decade of adult life,” Dr Monahan said.

“We thought the difference in functional outcomes would have narrowed over the years. That is, men with severe hemophilia should look more like those with

mild disorder, given improved therapeutics and access to care, but this wasn’t the case.”

“What needs examination is why, despite widespread availability of preventive and on-demand therapies for home use, we still see disparities. It speaks to the need for continued disease surveillance to monitor and inform hemophilia interventions and outcomes.”

Mortality

There were 551 deaths during the study period. The Era A and B cohorts accounted for 82% of the deaths in the severe hemophilia population and 96% of the deaths in the mild hemophilia population.

The researchers noted that liver failure has surpassed bleeding issues and HIV as the leading cause of death among US men with hemophilia.

Although there were no liver-related deaths in the 2 youngest cohorts, liver failure was the most commonly reported cause of death across all the cohorts, for both severe hemophilia (33% of deaths) and mild hemophilia (26% of deaths).

The researchers said this finding underscores the need to swiftly evaluate and treat HCV infections.

“Liver disease worsens bleeding, so eradicating hepatitis C infections needs to be a priority, especially as we now have remarkably effective therapies,” Dr Monahan said.

Across all the birth cohorts, hemophilia-related deaths accounted for 14.6% of deaths in patients with severe hemophilia and 10.7% of deaths in those with mild hemophilia.

Antihemophilic factor

A large study suggests that, despite treatment advances, men with severe hemophilia have not seen great reductions in bleeding events.

Data on more than 7000 men with hemophilia revealed substantial differences in the care received by men born before 1958 and those born between 1983

and 1992.

However, the data also showed that frequent bleeding was common in patients with severe hemophilia, regardless of when they were born.

These data were published in Blood.

“Our analysis provides a snapshot of how improvements in care have translated into outcomes across different generations of men with hemophilia,” said study author Paul E. Monahan, MD, of The University of North Carolina-Chapel Hill.

“While there is reason to be pleased with the progress we’ve made, our data show some surprising deficits and suggest that efforts are needed to more consistently apply the integration of standard-of-care multidisciplinary services and preventive blood clotting factor treatments to further normalize the lives of men living with hemophilia.”

Dr Monahan and his colleagues analyzed data on 7486 men—4899 with severe hemophilia (65.4%), 2587 with mild hemophilia (34.6%), 6094 with hemophilia A (81.4%), and 1392 with hemophilia B (18.6%).

The data were collected prospectively by the US Centers for Disease Control and Prevention and 130 federally supported Hemophilia Treatment Centers (HTCs) between 1998 and 2011. This represents the largest database of men living with hemophilia.

The researchers grouped the men into 4 eras (birth cohorts) to evaluate how outcomes—access to care, physical and social functioning, complications, and mortality—have changed over the last 50 years.

The cohorts were as follows:

• Era A: born before 1958 (median age 58)
• Era B: born between 1958 and 1975 (median age 40)
• Era C: born between 1976 and 1982 (median age 28)
• Era D: born between 1983 and 1992 (median age 21).

Access to care

The researchers found that the proportion of men who started home infusions before age 6 was far greater in Era D than Era A—50.4% and 2%, respectively. And the proportion of patients reporting a first HTC visit before age 2 rose nearly 10-fold from Era A to Era D—8.8% and 100%, respectively.

In addition, the use of a continuous prophylactic regimen was nearly 3-fold greater in Era D than Era A—46.7% and 16%, respectively.

However, patients in the youngest 2 birth cohorts were more likely than their older counterparts to be uninsured. The proportion of uninsured patients was 16.4% in Era D, 20.5% in Era C, 11.1% in Era B, and 5.7% in Era A.

Bleeding events

The proportion of patients reporting frequent bleeds decreased from Era A to Era D. However, frequent bleeding was common in men with severe hemophilia regardless of when they were born.

Even men from Era D—who had access to effective, safe clotting therapies and multidisciplinary care throughout their lifetimes—reported frequent bleeds.

The proportion of patients with severe hemophilia reporting 5 or more joint bleeds in the last 6 months was 42.6% in Era A and 35.5% in Era D. The proportion of patients with a joint affected by recurrent bleeding was 32.6% and 24.9%, respectively.

Functioning

The researchers also discovered that patients with severe hemophilia were 3 times as likely to report limitations in their activities or to be disabled, when compared to patients with mild hemophilia, regardless of when they were born.

Still, men from Era A were more likely to report limitations in their overall activity level—68.8% of severe hemophilia patients and 21.1% of mild hemophilia patients—than men from Era D—14.9% of severe hemophilia patients and 4.3% of mild hemophilia patients.

Men with severe hemophilia were more likely than men with mild hemophilia to report missing more than 10 days of work or school during the previous year. In Era A, the proportions were 6.9% and 2.6%, respectively. In Era D, the proportions were 5.6% and 3%, respectively.

“Clear disparities remain in terms of frequent bleeding and disability between men with severe hemophilia and mild hemophilia across every decade of adult life,” Dr Monahan said.

“We thought the difference in functional outcomes would have narrowed over the years. That is, men with severe hemophilia should look more like those with

mild disorder, given improved therapeutics and access to care, but this wasn’t the case.”

“What needs examination is why, despite widespread availability of preventive and on-demand therapies for home use, we still see disparities. It speaks to the need for continued disease surveillance to monitor and inform hemophilia interventions and outcomes.”

Mortality

There were 551 deaths during the study period. The Era A and B cohorts accounted for 82% of the deaths in the severe hemophilia population and 96% of the deaths in the mild hemophilia population.

The researchers noted that liver failure has surpassed bleeding issues and HIV as the leading cause of death among US men with hemophilia.

Although there were no liver-related deaths in the 2 youngest cohorts, liver failure was the most commonly reported cause of death across all the cohorts, for both severe hemophilia (33% of deaths) and mild hemophilia (26% of deaths).

The researchers said this finding underscores the need to swiftly evaluate and treat HCV infections.

“Liver disease worsens bleeding, so eradicating hepatitis C infections needs to be a priority, especially as we now have remarkably effective therapies,” Dr Monahan said.

Across all the birth cohorts, hemophilia-related deaths accounted for 14.6% of deaths in patients with severe hemophilia and 10.7% of deaths in those with mild hemophilia.

Antihemophilic factor

A large study suggests that, despite treatment advances, men with severe hemophilia have not seen great reductions in bleeding events.

Data on more than 7000 men with hemophilia revealed substantial differences in the care received by men born before 1958 and those born between 1983

and 1992.

However, the data also showed that frequent bleeding was common in patients with severe hemophilia, regardless of when they were born.

These data were published in Blood.

“Our analysis provides a snapshot of how improvements in care have translated into outcomes across different generations of men with hemophilia,” said study author Paul E. Monahan, MD, of The University of North Carolina-Chapel Hill.

“While there is reason to be pleased with the progress we’ve made, our data show some surprising deficits and suggest that efforts are needed to more consistently apply the integration of standard-of-care multidisciplinary services and preventive blood clotting factor treatments to further normalize the lives of men living with hemophilia.”

Dr Monahan and his colleagues analyzed data on 7486 men—4899 with severe hemophilia (65.4%), 2587 with mild hemophilia (34.6%), 6094 with hemophilia A (81.4%), and 1392 with hemophilia B (18.6%).

The data were collected prospectively by the US Centers for Disease Control and Prevention and 130 federally supported Hemophilia Treatment Centers (HTCs) between 1998 and 2011. This represents the largest database of men living with hemophilia.

The researchers grouped the men into 4 eras (birth cohorts) to evaluate how outcomes—access to care, physical and social functioning, complications, and mortality—have changed over the last 50 years.

The cohorts were as follows:

• Era A: born before 1958 (median age 58)
• Era B: born between 1958 and 1975 (median age 40)
• Era C: born between 1976 and 1982 (median age 28)
• Era D: born between 1983 and 1992 (median age 21).

Access to care

The researchers found that the proportion of men who started home infusions before age 6 was far greater in Era D than Era A—50.4% and 2%, respectively. And the proportion of patients reporting a first HTC visit before age 2 rose nearly 10-fold from Era A to Era D—8.8% and 100%, respectively.

In addition, the use of a continuous prophylactic regimen was nearly 3-fold greater in Era D than Era A—46.7% and 16%, respectively.

However, patients in the youngest 2 birth cohorts were more likely than their older counterparts to be uninsured. The proportion of uninsured patients was 16.4% in Era D, 20.5% in Era C, 11.1% in Era B, and 5.7% in Era A.

Bleeding events

The proportion of patients reporting frequent bleeds decreased from Era A to Era D. However, frequent bleeding was common in men with severe hemophilia regardless of when they were born.

Even men from Era D—who had access to effective, safe clotting therapies and multidisciplinary care throughout their lifetimes—reported frequent bleeds.

The proportion of patients with severe hemophilia reporting 5 or more joint bleeds in the last 6 months was 42.6% in Era A and 35.5% in Era D. The proportion of patients with a joint affected by recurrent bleeding was 32.6% and 24.9%, respectively.

Functioning

The researchers also discovered that patients with severe hemophilia were 3 times as likely to report limitations in their activities or to be disabled, when compared to patients with mild hemophilia, regardless of when they were born.

Still, men from Era A were more likely to report limitations in their overall activity level—68.8% of severe hemophilia patients and 21.1% of mild hemophilia patients—than men from Era D—14.9% of severe hemophilia patients and 4.3% of mild hemophilia patients.

Men with severe hemophilia were more likely than men with mild hemophilia to report missing more than 10 days of work or school during the previous year. In Era A, the proportions were 6.9% and 2.6%, respectively. In Era D, the proportions were 5.6% and 3%, respectively.

“Clear disparities remain in terms of frequent bleeding and disability between men with severe hemophilia and mild hemophilia across every decade of adult life,” Dr Monahan said.

“We thought the difference in functional outcomes would have narrowed over the years. That is, men with severe hemophilia should look more like those with

mild disorder, given improved therapeutics and access to care, but this wasn’t the case.”

“What needs examination is why, despite widespread availability of preventive and on-demand therapies for home use, we still see disparities. It speaks to the need for continued disease surveillance to monitor and inform hemophilia interventions and outcomes.”

Mortality

There were 551 deaths during the study period. The Era A and B cohorts accounted for 82% of the deaths in the severe hemophilia population and 96% of the deaths in the mild hemophilia population.

The researchers noted that liver failure has surpassed bleeding issues and HIV as the leading cause of death among US men with hemophilia.

Although there were no liver-related deaths in the 2 youngest cohorts, liver failure was the most commonly reported cause of death across all the cohorts, for both severe hemophilia (33% of deaths) and mild hemophilia (26% of deaths).

The researchers said this finding underscores the need to swiftly evaluate and treat HCV infections.

“Liver disease worsens bleeding, so eradicating hepatitis C infections needs to be a priority, especially as we now have remarkably effective therapies,” Dr Monahan said.

Across all the birth cohorts, hemophilia-related deaths accounted for 14.6% of deaths in patients with severe hemophilia and 10.7% of deaths in those with mild hemophilia.

Cancer patient

receiving treatment

Photo by Rhoda Baer

An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.

In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.

Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).

Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.

The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.

Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.

Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.

Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.

Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.

In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.

“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.

“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”

Cancer patient

receiving treatment

Photo by Rhoda Baer

An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.

In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.

Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).

Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.

The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.

Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.

Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.

Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.

Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.

In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.

“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.

“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”

Cancer patient

receiving treatment

Photo by Rhoda Baer

An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.

In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.

Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).

Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.

The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.

Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.

Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.

Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.

Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.

In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.

“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.

“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”

Bottles of warfarin

Photo courtesy of NIGMS

Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.

Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.

But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.

Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.

The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.

To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.

The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.

In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.

The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.

When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).

Still, the researchers said they observed a plateau in oral anticoagulant prescription.

The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.

Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.

Bottles of warfarin

Photo courtesy of NIGMS

Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.

Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.

But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.

Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.

The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.

To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.

The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.

In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.

The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.

When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).

Still, the researchers said they observed a plateau in oral anticoagulant prescription.

The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.

Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.

Bottles of warfarin

Photo courtesy of NIGMS

Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.

Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.

But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.

Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.

The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.

To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.

The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.

In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.

The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.

When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).

Still, the researchers said they observed a plateau in oral anticoagulant prescription.

The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.

Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”