Anemia

Image by Marquet Minor

Gene editing has revealed how dyskeratosis congenita (DC) impairs the formation of blood cells, according to research published in Stem Cell Reports.

The discovery has opened up new lines of investigation into how to treat DC, which is characterized by shortened telomeres.

“Lengthening telomeres seems like a logical way to help these patients, but it could possibly come with its own set of problems,” said study author Luis F.Z. Batista, PhD, of the Washington University School of Medicine in St. Louis, Missouri.

“We would worry about encouraging cancer formation, for example, as high levels of the protein that lengthens telomeres—telomerase—are commonly found with cancer. But if we could find a way to block the signaling pathways that short telomeres activate—that specifically lead to the problems in blood cell formation—it could allow these patients to continue making blood cells.”

With this in mind, Dr Batista and his colleagues used CRISPR to edit into human embryonic stem cells a pair of mutations associated with DC— DKC1_A353V and TERT_P704S. These cells reproduced the telomere-shortening defect seen in patients with DC.

With this model, the researchers showed how the telomere defect leads to the gradual loss of blood cell formation and how blocking the downstream effects of the defect can reverse this loss, leading to normal production of blood cells.

Blocking this signaling pathway did not lengthen telomeres or stop their shortening, but it allowed the manufacturing of different types of blood cells to continue.

The researchers also made a discovery that provides a distinction regarding the detrimental effect of short telomeres during early development. The team found the defect did not hinder primitive hematopoiesis, but it did impair definitive hematopoiesis.

“This was tremendously interesting from a developmental biology perspective as well as from a disease modeling perspective,” said study author Christopher M. Sturgeon, PhD, of the Washington University School of Medicine. “We now have a platform to really dig deeper into understanding the mechanisms behind some forms of bone marrow failure.”

The researchers implicated high levels of the protein p53 as one of the signals that leads to the drop in definitive hematopoiesis.

“P53 is thought of as a guardian of the genome,” Dr Batista noted. “Mutations that disable p53 are associated with different types of cancer. Because of this, we would not consider directly trying to block p53 in these patients.”

“But what this study provides is proof-of-concept that this pathway is involved in this response. So we now are looking for ways to block the pathway further downstream without necessarily blocking p53 directly.”

Drs Batista and Sturgeon recently received a grant from the Department of Defense to investigate the pathway. The pair believes the strategy used in this study could be relevant for other bone marrow failure syndromes as well, such as Fanconi anemia and aplastic anemia.

Image by Marquet Minor

Gene editing has revealed how dyskeratosis congenita (DC) impairs the formation of blood cells, according to research published in Stem Cell Reports.

The discovery has opened up new lines of investigation into how to treat DC, which is characterized by shortened telomeres.

“Lengthening telomeres seems like a logical way to help these patients, but it could possibly come with its own set of problems,” said study author Luis F.Z. Batista, PhD, of the Washington University School of Medicine in St. Louis, Missouri.

“We would worry about encouraging cancer formation, for example, as high levels of the protein that lengthens telomeres—telomerase—are commonly found with cancer. But if we could find a way to block the signaling pathways that short telomeres activate—that specifically lead to the problems in blood cell formation—it could allow these patients to continue making blood cells.”

With this in mind, Dr Batista and his colleagues used CRISPR to edit into human embryonic stem cells a pair of mutations associated with DC— DKC1_A353V and TERT_P704S. These cells reproduced the telomere-shortening defect seen in patients with DC.

With this model, the researchers showed how the telomere defect leads to the gradual loss of blood cell formation and how blocking the downstream effects of the defect can reverse this loss, leading to normal production of blood cells.

Blocking this signaling pathway did not lengthen telomeres or stop their shortening, but it allowed the manufacturing of different types of blood cells to continue.

The researchers also made a discovery that provides a distinction regarding the detrimental effect of short telomeres during early development. The team found the defect did not hinder primitive hematopoiesis, but it did impair definitive hematopoiesis.

“This was tremendously interesting from a developmental biology perspective as well as from a disease modeling perspective,” said study author Christopher M. Sturgeon, PhD, of the Washington University School of Medicine. “We now have a platform to really dig deeper into understanding the mechanisms behind some forms of bone marrow failure.”

The researchers implicated high levels of the protein p53 as one of the signals that leads to the drop in definitive hematopoiesis.

“P53 is thought of as a guardian of the genome,” Dr Batista noted. “Mutations that disable p53 are associated with different types of cancer. Because of this, we would not consider directly trying to block p53 in these patients.”

“But what this study provides is proof-of-concept that this pathway is involved in this response. So we now are looking for ways to block the pathway further downstream without necessarily blocking p53 directly.”

Drs Batista and Sturgeon recently received a grant from the Department of Defense to investigate the pathway. The pair believes the strategy used in this study could be relevant for other bone marrow failure syndromes as well, such as Fanconi anemia and aplastic anemia.

Image by Marquet Minor

Gene editing has revealed how dyskeratosis congenita (DC) impairs the formation of blood cells, according to research published in Stem Cell Reports.

The discovery has opened up new lines of investigation into how to treat DC, which is characterized by shortened telomeres.

“Lengthening telomeres seems like a logical way to help these patients, but it could possibly come with its own set of problems,” said study author Luis F.Z. Batista, PhD, of the Washington University School of Medicine in St. Louis, Missouri.

“We would worry about encouraging cancer formation, for example, as high levels of the protein that lengthens telomeres—telomerase—are commonly found with cancer. But if we could find a way to block the signaling pathways that short telomeres activate—that specifically lead to the problems in blood cell formation—it could allow these patients to continue making blood cells.”

With this in mind, Dr Batista and his colleagues used CRISPR to edit into human embryonic stem cells a pair of mutations associated with DC— DKC1_A353V and TERT_P704S. These cells reproduced the telomere-shortening defect seen in patients with DC.

With this model, the researchers showed how the telomere defect leads to the gradual loss of blood cell formation and how blocking the downstream effects of the defect can reverse this loss, leading to normal production of blood cells.

Blocking this signaling pathway did not lengthen telomeres or stop their shortening, but it allowed the manufacturing of different types of blood cells to continue.

The researchers also made a discovery that provides a distinction regarding the detrimental effect of short telomeres during early development. The team found the defect did not hinder primitive hematopoiesis, but it did impair definitive hematopoiesis.

“This was tremendously interesting from a developmental biology perspective as well as from a disease modeling perspective,” said study author Christopher M. Sturgeon, PhD, of the Washington University School of Medicine. “We now have a platform to really dig deeper into understanding the mechanisms behind some forms of bone marrow failure.”

The researchers implicated high levels of the protein p53 as one of the signals that leads to the drop in definitive hematopoiesis.

“P53 is thought of as a guardian of the genome,” Dr Batista noted. “Mutations that disable p53 are associated with different types of cancer. Because of this, we would not consider directly trying to block p53 in these patients.”

“But what this study provides is proof-of-concept that this pathway is involved in this response. So we now are looking for ways to block the pathway further downstream without necessarily blocking p53 directly.”

Drs Batista and Sturgeon recently received a grant from the Department of Defense to investigate the pathway. The pair believes the strategy used in this study could be relevant for other bone marrow failure syndromes as well, such as Fanconi anemia and aplastic anemia.

Image by Erhabor Osaro

The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About caplacizumab

Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.

Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.

The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.

The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.

There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.

The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.

A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.

In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.

There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.

Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.

Image by Erhabor Osaro

The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About caplacizumab

Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.

Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.

The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.

The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.

There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.

The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.

A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.

In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.

There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.

Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.

Image by Erhabor Osaro

The US Food and Drug Administration (FDA) has granted fast track designation to caplacizumab, an anti-von Willebrand factor (vWF) nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologics license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About caplacizumab

Caplacizumab is a bivalent anti-vWF nanobody being developed by Ablynx. Caplacizumab works by blocking the interaction of ultra-large vWF multimers with platelets, having an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction that occurs in patients with aTTP.

Researchers evaluated the efficacy and safety of caplacizumab, given with standard care for aTTP, in the phase 2 TITAN trial.

The trial enrolled 75 patients with aTTP. They all received the standard of care—daily plasma exchange and immunosuppressive therapy. Thirty-six patients were randomized to receive caplacizumab as well, and 39 were randomized to placebo.

The study’s primary endpoint was time to response (platelet count normalization). Patients in the caplacizumab arm had a 39% reduction in the median time to response compared to patients in the placebo arm (P=0.005).

The rate of confirmed response was 86.1% (n=31) in the caplacizumab arm and 71.8% (n=28) in the placebo arm.

There were more relapses in the caplacizumab arm than the placebo arm—8 (22.2%) and 0, respectively. Relapse was defined as a TTP event occurring more than 30 days after the end of daily plasma exchange.

There were fewer exacerbations in the caplacizumab arm than the placebo arm—3 (8.3%) and 11 (28.2%), respectively. Exacerbation was defined as recurrent thrombocytopenia within 30 days of the end of daily plasma exchange that required re-initiation of daily exchange.

The rate of adverse events thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of events that were possibly related was 54% and 8%, respectively.

A lower proportion of subjects in the caplacizumab arm experienced one or more major thromboembolic events or died, compared to the placebo arm—11.4% and 43.2%, respectively.

In addition, fewer caplacizumab-treated patients were refractory to treatment—5.7% vs 21.6%.

There were 2 deaths in the placebo arm, and both of those patients were refractory to treatment. There were no deaths reported in the caplacizumab arm.

Now, researchers are evaluating caplacizumab in the phase 3 HERCULES trial (NCT02553317). Results from this study are anticipated in the second half of 2017 are expected to support a planned biologics license application filing in the US in 2018.

AML cells

Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.

The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.

The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.

And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.

Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.

In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.

The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.

The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.

The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.

Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.

The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.

DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.

In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

AML cells

Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.

The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.

The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.

And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.

Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.

In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.

The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.

The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.

The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.

Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.

The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.

DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.

In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

AML cells

Researchers say they have determined which patients will respond to treatment with SY-1425, a retinoic acid receptor alpha (RARα) agonist.

The team discovered a subset of patients with acute myeloid leukemia (AML) who had a super-enhancer associated with the RARA gene, which is predictive of response to SY-1425.

The researchers also identified a subset of patients with myelodysplastic syndromes (MDS) who had high expression of the RARA gene.

And experiments showed that RARA-high MDS had a similar response to SY-1425 as that seen in AML driven by the RARA super-enhancer.

Ravindra Majeti MD, PhD, of Stanford University School of Medicine in California, and colleagues reported these findings in Cancer Discovery. Employees of Syros Pharmaceuticals, the company developing SY-1425, were also involved in this research.

In collaboration with the Majeti lab, Syros used its gene control platform to analyze 66 AML patients’ tumor samples. In this way, the researchers identified 6 distinct patient subsets based on super-enhancer profiles, including 1 enriched for a super-enhancer associated with the RARA gene.

The team found that super-enhancer profiles were strongly associated with survival outcomes, often independent of known genetic mutations in AML.

The RARA super-enhancer was associated with high expression of the RARA gene, which codes for a transcription factor targeted by SY-1425.

The RARA super-enhancer was predictive of response to SY-1425. In AML cells with high RARA expression, SY-1425 reduced proliferation and promoted differentiation.

Moreover, SY-1425 decreased tumor burden and prolonged survival in patient-derived xenograft models of AML with high RARA expression. However, there was no effect on AML cells or models with low RARA expression.

The researchers said SY-1425 induced profound transcriptional changes promoting cell differentiation in AML cells with high RARA expression, but the drug produced little to no transcriptional changes in AML cells with low RARA expression.

DHRS3 was the most strongly and rapidly induced gene in response to treatment with SY-1425. This led to the identification of DHRS3 induction as an early indicator of whether SY-1425 is affecting the targeted biology in defined subsets of AML and MDS patients. It is therefore used as a pharmacodynamic marker in the ongoing phase 2 trial of SY-1425.

In this trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as testing SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

Photo by Graham Colm

Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.

The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).

Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).

Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.

In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.

QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.

The disorders covered by QHerit include:

QHerit is now available for order by US physicians. For more information, visit www.QHerit.com.

Photo by Graham Colm

Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.

The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).

Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).

Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.

In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.

QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.

The disorders covered by QHerit include:

QHerit is now available for order by US physicians. For more information, visit www.QHerit.com.

Photo by Graham Colm

Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.

The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).

Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).

Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.

In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.

QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.

The disorders covered by QHerit include:

QHerit is now available for order by US physicians. For more information, visit www.QHerit.com.

Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.

The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.

“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”

Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.

After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.

Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.

Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.

Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.

Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.

The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.

“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”

Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.

After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.

Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.

Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.

Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.

Matching down to the allele level in umbilical cord blood transplantation between unrelated donors results in greater overall survival for those with nonmalignant diseases, such as aplastic anemia, researchers found in a retrospective study published in the Lancet Haematology.

The review (Lancet Haematol. 2017 Jul;4[7]:e325-33), the largest published on the topic, indicates that clinicians should change practice from the current standard of antigen-level matching, said Mary Eapen, MD, director of the Center for International Blood and Marrow Transplant Research (CIBMTR) in Wauwatosa, Wisconsin.

“Our findings,” Dr. Eapen wrote, “support a change in clinical practice to prioritization of units on allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1.”

Data were pulled from cases reported to the Center for International Blood and Marrow Transplant Research or the European Group for Blood and Marrow Transplant. Researchers looked at 1,199 donor-recipient matches of cord blood transplantation for diseases, such as severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency, inborn errors of metabolism, severe aplastic anemia, and Fanconi anemia. Recipients could be as old as age 16, but most were age 5 or younger.

After adjustment for factors, including cytomegalovirus serostatus, the intensity of the conditioning regimen, and the total nucleated cell dose, the 5-year overall survival was 79% for transplants that were matched at all eight alleles at HLA-A, HLA-B, HLA-C and HLA-DRB1. These results compare with 76% after transplants with one mismatch, 70% with two mismatches, 62% with three mismatches, and 49% with 4 or more mismatches.

Mortality risks were significantly higher for patients who received transplants with two (P = .018), three (P = .0001), and four or more mismatches (P less than .0001), compared with those whose transplants were fully matched. There was no difference statistically between full matches and one mismatch, but the findings suggest that the mortality risk might prove significant with a larger sample size.

Researchers cautioned that, because most patients were age 5 or younger, the results might not be generalizable to older children.

Although HLA typing is available at CIBMTR for most blood cord transplants for nonmalignant diseases, full allele matches or just one mismatch are not the norm, Dr. Eapen wrote. Researchers said that they suspect this is because of difficulties finding matches or because a high total nucleated cell count is prioritized above HLA matching. They suggest clinicians change their decision making in this regard.

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

Micrograph showing MDS

Research published in Cell Reports helps explain why some patients with myelodysplastic syndrome (MDS) do not respond to treatment with azacitidine.

The study showed that patients who were resistant to the drug had relatively quiescent hematopoietic progenitor cells (HPCs).

A smaller proportion of their HPCs were undergoing active cell-cycle progression when compared to the HPCs of patients who responded to azacitidine.

This discovery could provide the first method to identify non-responders to azacitidine early, according to study author Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.

“These are early days, but this could avoid what has really been a ‘wait and see’ approach with patients that sometimes results in them receiving futile treatment for 6 months,” Dr Unnikrishnan said.

“By that stage, the patient’s disease has progressed, and there’s no alternative for them.”

Dr Unnikrishnan and his colleagues also found the HPC quiescence in non-responders was mediated by integrin α5 (ITGA5) signaling, and the cells’ hematopoietic potential improved when the team combined azacitidine treatment with an ITGA5 inhibitor.

This suggests a potential avenue for future combination therapies that would improve azacitidine responsiveness.

Lastly, the researchers made discoveries that could explain why some patients who initially respond to azacitidine eventually relapse.

“All of the pernicious mutations that we associate with MDS never disappear in these patients, even after years of treatment,” Dr Unnikrishnan said. “From a clinical perspective, blood cell production is restored in patients, but they are a ticking time bomb, waiting to relapse.”

“[Azacitidine] is not a cure, and we are starting to understand why it does what it does. We need to find better treatments than azacitidine if we want a more durable therapy for MDS, and that’s the basis for our future work.”

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

Photo by Juan D. Alfonso

A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.

Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.

However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.

Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.

Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.

The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.

PLOS ONE study

The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.

Eight percent of all subjects (n=494) had iron deficiency.

Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.

The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.

All of these factors have been associated with iron-deficiency anemia in women in prior studies.

In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.

Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).

The Journal of Pediatrics study

In this study, the researchers looked at whether a questionnaire could better predict iron status.

The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.

This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.

Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.

Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.

Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.

Conclusions

The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.

“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.

She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.

Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.

This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said.

Photo by Juan D. Alfonso

A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.

Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.

However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.

Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.

Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.

The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.

PLOS ONE study

The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.

Eight percent of all subjects (n=494) had iron deficiency.

Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.

The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.

All of these factors have been associated with iron-deficiency anemia in women in prior studies.

In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.

Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).

The Journal of Pediatrics study

In this study, the researchers looked at whether a questionnaire could better predict iron status.

The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.

This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.

Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.

Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.

Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.

Conclusions

The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.

“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.

She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.

Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.

This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said.

Photo by Juan D. Alfonso

A pair of studies suggest physicians should consider testing female adolescents for iron deficiency within a few years of starting menses.

Women are typically tested for anemia in their teens, with a quick and affordable hemoglobin test.

However, iron deficiency can develop years before anemia and can be missed by hemoglobin testing alone.

Blood tests for iron deficiency without anemia are more costly and more difficult to obtain than hemoglobin testing for anemia.

Deepa Sekhar, MD, of Penn State College of Medicine in Hershey, Pennsylvania, and her colleagues set out to determine risk factors for iron deficiency without anemia in order to pinpoint which women could benefit most from the more costly testing.

The results of the researchers’ 2 studies were published in PLOS ONE and The Journal of Pediatrics.

PLOS ONE study

The researchers evaluated data from 6216 females, ages 12 to 49, who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. As part of the survey, participants were tested for both iron deficiency and anemia.

Eight percent of all subjects (n=494) had iron deficiency.

Nine percent (n=250) of non-anemic younger women (ages 12-21) had iron deficiency, as did 7% (n=244) of older women (ages 22-49) who were not anemic.

The researchers looked at potential risk factors for iron deficiency, including the age when women started menstruating, as well as their race/ethnicity, poverty status, food insecurity, tobacco or nicotine use, dietary information, body mass index, and physical activity.

All of these factors have been associated with iron-deficiency anemia in women in prior studies.

In this study, there was only 1 risk factor significantly associated with iron deficiency without anemia.

Young women (ages 12-21) who had been menstruating for more than 3 years had a significantly higher risk of iron deficiency without anemia (risk ratio=3.18).

The Journal of Pediatrics study

In this study, the researchers looked at whether a questionnaire could better predict iron status.

The questionnaire included questions on depression, poor attention, and daytime sleepiness, all of which have been associated with iron deficiency or iron-deficiency anemia, but were not captured in the prior NHANES analyses.

This questionnaire was compared to the 4 questions assessing iron-deficiency anemia risk in the Bright Futures Adolescent Previsit Questionnaire, a survey recommended for physician use by the American Academy of Pediatrics.

Ninety-six female adolescents participated in this study. Eighteen percent of them (n=17) had iron deficiency, and 5% (n=5) had iron-deficiency anemia.

Both the Bright Futures questions and the researchers’ risk assessment questionnaire poorly predicted ferritin and hemoglobin values in these subjects.

Mean differences in depression, poor attention, food insecurity, daytime sleepiness, and body mass index percentile were not significantly associated with ferritin or hemoglobin.

Conclusions

The results of these 2 studies suggest that risk factors and assessments cannot accurately determine which young women should receive testing for iron deficiency, although results from the first study might be used to determine when testing should occur.

“I think we need to establish the optimal timing for an objective assessment of adolescent iron deficiency and anemia,” Dr Sekhar said.

She believes the appropriate age may be 16 years old, when most females will have been menstruating for at least 3 years.

Further research will be needed to determine which blood test for iron deficiency without anemia is accurate, cost-efficient, and practical for routine doctor’s office use.

This test should be given with hemoglobin testing to catch all young women on the spectrum of iron deficiency, Dr Sekhar said.

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).