HT Staff

Photo by Rhoda Baer

A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.

The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.

However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.

Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.

“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.

“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”

For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.

The researchers ranked 45 countries according to the level of malaria research funding they received.

All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.

However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.

In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).

The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.

Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.

“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”

“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”

Photo by Rhoda Baer

A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.

The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.

However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.

Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.

“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.

“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”

For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.

The researchers ranked 45 countries according to the level of malaria research funding they received.

All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.

However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.

In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).

The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.

Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.

“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”

“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”

Photo by Rhoda Baer

A new study has revealed inequalities in malaria research funding in sub-Saharan Africa.

The study showed that some countries with a high malaria burden—such as Sierra Leone, Congo, Central African Republic, and Guinea—received little to no funding for malaria research in recent years.

However, other countries—such as Tanzania, Uganda, and Kenya—received close to $100 million in funding for malaria research.

Michael Head, PhD, of the University of Southampton in the UK, and his colleagues reported these findings in The Lancet Global Health.

“We have been able to provide a comprehensive overview of the landscape of funding for malaria in sub-Saharan Africa, a massive area where around 90% of worldwide malaria cases occur,” Dr Head said.

“We’ve shown that there are countries that are being neglected, and the global health community should reconsider strategies around resource allocation to reduce inequities and improve equality.”

For this study, Dr Head and his colleagues analyzed funding data spanning the period from 1997 to 2013. The data were sourced from 13 major public and philanthropic global health funders, as well as from funding databases.

The researchers ranked 45 countries according to the level of malaria research funding they received.

All of the countries studied received funding for malaria control, which includes investment for bed nets, public health schemes, and antimalarial drugs.

However, 8 of the 45 countries did not receive any funding related to malaria research. This included Central African Republic, Sierra Leone, and Congo—countries with a “reasonably high” malaria burden/mortality rate, according to Dr Head and his colleagues.

In all, there were 333 research awards, totaling $814.4 million. The countries that received the most research funding were Tanzania ($107.8 million), Uganda ($97.9 million), and Kenya ($92.9 million).

The 8 countries that received no research funding were Cape Verde, Botswana, Djibouti, Central African Republic, Mauritania, Congo, Chad, and Sierra Leone.

Dr Head and his colleagues suggested that the reason for the disparity in funding allocation could be, in part, due to the presence of established high-quality research infrastructure in countries such as Tanzania and Kenya, and political instability and poor healthcare infrastructures in lower-ranked nations such as Central African Republic or Sierra Leone.

“[N]ew investment in malaria research and development in these areas can encourage the development of improved health systems,” Dr Head said. “Many countries in sub-Saharan Africa simply do not have an established research infrastructure, and it is difficult for research funders to make investments in these settings.”

“Ultimately, however, there are neglected populations in these countries who suffer greatly from malaria and other diseases. Investments in health improve the wealth of a nation, and we need to be smarter with allocating limited resources to best help to reduce clear health inequalities.”

Children’s Research Hospital

Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).

The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.

Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.

“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.

“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”

Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.

“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.

“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”

The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.

In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.

“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.

He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.

“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.

Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.

Children’s Research Hospital

Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).

The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.

Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.

“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.

“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”

Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.

“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.

“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”

The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.

In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.

“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.

He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.

“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.

Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.

Children’s Research Hospital

Researchers say they have uncovered new details of the genomic landscape of T-lineage acute lymphoblastic leukemia (T-ALL).

The team believes their findings will aid the development of drugs to target newly discovered mutations and enable researchers to engineer better mouse models to probe the leukemia’s aberrant biological machinery.

Charles Mullighan, MD, MBBS, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported their findings in Nature Genetics.

“This first comprehensive and systematic analysis in a large group of patients revealed many new mutations that are biologically significant as well as new drug targets that could be clinically important,” Dr Mullighan said.

“Leukemias typically arise from multiple genetic changes that work together. Most previous studies have not had the breadth of genomic data in enough patients to identify the constellations of mutations and recognize their associations.”

Dr Mullighan and his colleagues sequenced the genomes of 264 children and young adults with T-ALL. This revealed 106 driver genes, half of which had not been identified in childhood T-ALL.

“We went into this study knowing that we didn’t know the full genomic landscape of T-ALL,” said Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.

“But we were surprised that over half of the new targets and mutations were previously unrecognized. It was particularly unexpected and very striking that some mutations were exclusively found in some subtypes of T-ALL but not others.”

The researchers’ analysis confirmed that T-ALL was driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. However, the study also revealed new mutations in those known pathways.

In addition, the researchers identified cases in which the same T-ALL subtype had mutations in different pathways triggered by the same founding mutation.

“We believe this finding suggests we can target such subtypes with an inhibitor drug for one of the pathways, and it’s likely to be effective,” Dr Mullighan said.

He and his colleagues also believe the mutations uncovered in this study will enable researchers to create mouse models that more accurately reflect human T-ALL.

“We now have a launching pad, if you will, to design mouse models that include multiple genetic mutations to more faithfully reflect the leukemias we see in humans,” Dr Mullighan said.

Data from this study are available to researchers through the St. Jude PeCan data portal and the TARGET Data Matrix.

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab ozogamicin arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab ozogamicin and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab ozogamicin arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab ozogamicin arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab ozogamicin arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab ozogamicin arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab ozogamicin, and 2 were thought to be related to chemotherapy.

Photo by Graham Colm

The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.

This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.

The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.

The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.

ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.

The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.

The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.

The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.

Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.

The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.

Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.

These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.

The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.

Photo by Graham Colm

The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.

This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.

The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.

The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.

ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.

The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.

The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.

The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.

Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.

The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.

Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.

These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.

The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.

Photo by Graham Colm

The US Food and Drug Administration (FDA) has allowed marketing of the ClearLLab Reagent Panel, a combination of conjugated antibody cocktails designed to aid the detection of hematopoietic neoplasia.

This includes chronic and acute leukemias, non-Hodgkin lymphoma, myeloma, myelodysplastic syndromes, and myeloproliferative neoplasms.

The ClearLLab reagents are intended for in vitro diagnostic use to identify various cell populations by immunophenotyping on an FC 500 flow cytometer.

The reagents are directed against B, T, and myeloid lineage antigens and intended to identify relevant leukocyte surface molecules.

ClearLLab provides 2 T-cell tubes, 2 B-cell tubes, and a myeloid tube, each consisting of pre-mixed 4- to 5-color cocktails. Together, this totals 18 markers as directly conjugated antibodies.

The reagents can be used with peripheral whole blood, bone marrow, and lymph node specimens.

The results obtained via testing with the ClearLLab reagents should be interpreted along with additional clinical and laboratory findings, according to Beckman Coulter, Inc., the company that will be marketing the reagents.

The FDA reviewed data for the ClearLLab reagents through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

The FDA’s clearance of the ClearLLab reagents was supported by a study designed to demonstrate the reagents’ performance, which was conducted on 279 samples at 4 independent clinical sites.

Results with the ClearLLab reagents were compared to results with alternative detection methods used at the sites.

The ClearLLab results aligned with the study sites’ final diagnosis 93.4% of the time and correctly detected abnormalities 84.2% of the time.

Along with its clearance of the ClearLLab reagents, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the reagents’ accuracy, reliability, and clinical relevance.

These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab reagents and similar tools.

The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Image by Betty Pace

The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.

GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).

GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.

About PRIME

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

Phase 1/2 trial

The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.

Data from this trial were presented at the 2016 ASH Annual Meeting.

At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.

All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.

Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).

Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).

The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.

No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).

Image by Betty Pace

The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.

GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).

GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.

About PRIME

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

Phase 1/2 trial

The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.

Data from this trial were presented at the 2016 ASH Annual Meeting.

At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.

All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.

Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).

Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).

The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.

No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).

Image by Betty Pace

The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.

GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).

GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.

If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.

About PRIME

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

Phase 1/2 trial

The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.

Data from this trial were presented at the 2016 ASH Annual Meeting.

At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.

All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.

Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).

Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).

The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.

No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Photo by Bill Branson

WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).

The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.

They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.

Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).

NEPA is a combination of the selective NK₁RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT₃RA, palonosetron (0.5 mg) for the prevention of CINV.

Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.

Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

It is formulated into a single oral capsule.

Study design

The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.

Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).

All patients received oral dexamethasone on days 1-4.

The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.

The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at  ̶ 10%.

Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).

Results

The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.

The most common cancer types were lung and head and neck cancer.

Patients had received a median cisplatin dose of 73 and 72 mg/m² in the NEPA and APR/GRAN arms, respectively.

Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).

In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).

Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).

Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.

However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.

Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.

Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.

The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.

Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.

The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.

NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.

For the full US prescribing information, see the package insert.

Photo by Bill Branson

WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).

The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.

They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.

Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).

NEPA is a combination of the selective NK₁RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT₃RA, palonosetron (0.5 mg) for the prevention of CINV.

Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.

Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

It is formulated into a single oral capsule.

Study design

The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.

Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).

All patients received oral dexamethasone on days 1-4.

The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.

The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at  ̶ 10%.

Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).

Results

The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.

The most common cancer types were lung and head and neck cancer.

Patients had received a median cisplatin dose of 73 and 72 mg/m² in the NEPA and APR/GRAN arms, respectively.

Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).

In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).

Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).

Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.

However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.

Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.

Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.

The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.

Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.

The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.

NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.

For the full US prescribing information, see the package insert.

Photo by Bill Branson

WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).

The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.

They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.

Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).

NEPA is a combination of the selective NK₁RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT₃RA, palonosetron (0.5 mg) for the prevention of CINV.

Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.

Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

It is formulated into a single oral capsule.

Study design

The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.

Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).

All patients received oral dexamethasone on days 1-4.

The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.

The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at  ̶ 10%.

Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).

Results

The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.

The most common cancer types were lung and head and neck cancer.

Patients had received a median cisplatin dose of 73 and 72 mg/m² in the NEPA and APR/GRAN arms, respectively.

Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).

In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).

Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).

Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.

However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.

Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.

Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.

The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.

Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.

The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.

NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.

For the full US prescribing information, see the package insert.