Anemia

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Gene and Cell Therapy

George Stamatoyannopoulos, MD, who conducted important research into hemoglobinopathies, passed away this month at the age of 84.

Dr Stamatoyannopoulos’s research encompassed human genetics and hematology, including the structure and function of hemoglobinopathies, the genetics of thalassemia, and the molecular and cellular control of globin gene switching.

For much of his career, Dr Stamatoyannopoulos focused on the development of gene therapy for hemoglobinopathies and other disorders.

Dr Stamatoyannopoulos was born in Athens, Greece, on March 11, 1934. He entered medical school in Athens at age 17 and graduated at the top of his class 7 years later.

After his medical training, Dr Stamatoyannopoulos pursued thesis research on inherited blood disorders, particularly anemias.

Dr Stamatoyannopoulos performed the first large-scale molecular geographical survey of a genetic trait, which revealed the relationship between malaria and both thalassemia and sickle cell traits.

Dr Stamatoyannopoulos also discovered that fetal hemoglobin could ameliorate the effects of thalassemia. His theory that thalassemia and sickle cell anemia could be treated by re-activating fetal hemoglobin has underpinned decades of efforts to cure these disorders.

As a young investigator, Dr Stamatoyannopoulos expanded genetic studies of blood diseases in Greece, where his work drew the attention of medical genetics pioneer Arno Motulsky, MD.

Dr Motulsky recruited Dr Stamatoyannopoulos to the University of Washington (Seattle) in 1964. Dr Stamatoyannopoulos became a full professor there in 1973, founded the Markey Molecular Medicine Center, and was chief of medical genetics from 1989 to 2005.

Dr Stamatoyannopoulos organized the founding of the American Society of Gene and Cell Therapy. His contributions were recognized by establishment of the Stamatoyannopoulos lecture, the society’s highest award.

Dr Stamatoyannopoulos also served as president of the American Society of Hematology (1992) and president of the American Society of Gene and Cell Therapy (1996). He held leadership positions in other medical and scientific societies as well.

Dr Stamatoyannopoulos authored more than 420 scientific papers and 14 books, including The Molecular Basis of Blood Diseases.

Dr Stamatoyannopoulos died June 16, 2018. He is survived by his wife and collaborator Thalia Papayannopoulou, MD, (a professor of medicine and internationally recognized hematologist), 2 sons, and 3 grandchildren.

Photo from EHA

STOCKHOLM—Results of a phase 3 study suggest the long-acting C5 complement inhibitor ravulizumab produces similar results as eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Treatment with ravulizumab every 8 weeks proved noninferior to treatment with eculizumab every 2 weeks for the co-primary endpoints of transfusion avoidance and hemolysis as measured by lactate dehydrogenase (LDH) normalization.

Ravulizumab also proved noninferior with regard to secondary efficacy endpoints and had a safety profile similar to that of eculizumab.

These results suggest ravulizumab could be a more convenient alternative for PNH patients, according to Jong Wook Lee, MD, of Seoul St. Mary’s Hospital in Seoul, South Korea.

Dr Lee presented these results as a late-breaking abstract (LB2603) at the 23rd Congress of the European Hematology Association (EHA).

The study was sponsored by Alexion Pharmaceuticals.

The trial enrolled adults with PNH naive to complement inhibitor therapy. They were randomized to receive ravulizumab (n=125) or eculizumab (n=121) for 183 days.

More than half of patients were male—52% in the ravulizumab arm and 57% in the eculizumab arm.  Most patients were Asian (57.6% in the ravulizumab arm and 47.1% in the eculizumab arm) or white (34.4% and 42.1%, respectively).

Patients’ mean age at first infusion was 44.8 in the ravulizumab arm and 46.2 in the eculizumab arm. The mean number of years from PNH diagnosis to consent was 6.7 and 6.4, respectively.

The mean LDH at baseline was 1634 U/L in the ravulizumab arm and 1578 U/L in the eculizumab arm. The mean FACIT-Fatigue score was 36.7 and 36.9, respectively.

All 125 ravulizumab patients completed 26 weeks of treatment, as did 119 of the eculizumab patients. One hundred twenty-four ravulizumab patients entered the extension phase, as did 119 eculizumab patients.

Efficacy

The study’s primary efficacy endpoints were transfusion avoidance and LDH normalization from day 29 to 183. Dr Lee said ravulizumab proved noninferior to eculizumab for both endpoints, and point estimates favored ravulizumab.

The proportion of patients who remained transfusion-free was 73.6% in the ravulizumab arm and 66.1% in the eculizumab arm (difference, 6.8; 95% CI, -4.66, 18.14).

The proportion of patients who achieved LDH normalization was 53.6% and 49.4%, respectively (difference, 1.19; 95% CI, 0.8, 1.77).

Secondary efficacy endpoints included the percentage change in LDH from baseline, change in FACIT-Fatigue score from baseline, and the proportions of patients with breakthrough hemolysis and stabilized hemoglobin.

Again, ravulizumab was noninferior to eculizumab for all endpoints, with point estimates favoring ravulizumab.

The LDH percentage change was -76.84% in the ravulizumab arm and -76.02% in the eculizumab arm (difference, 0.83; 95% CI, -3.56, 5.21).

The change (improvement) in FACIT-Fatigue score was 7.07 and 6.40, respectively (difference, 0.67; 95% CI, -1.21, 2.55).

The percentage of patients with hemoglobin stabilization was 68.0% in the ravulizumab arm and 64.5% in the eculizumab arm (difference, 2.9; 95% CI, -8.80, 14.64).

The percentage of patients with breakthrough hemolysis was 4.0% and 10.7%, respectively (difference, 6.7; 95% CI, -0.18, 14.21).

Dr Lee noted that the proportion of patients with breakthrough hemolysis was more than 2.5-fold higher in the eculizumab arm than the ravulizumab arm—13 patients with 15 events and 5 patients with 5 events, respectively.

He said this was likely due to the immediate, complete, and sustained inhibition of C5 (mean free C5 <0.5 μg/mL) achieved by ravulizumab. Complete inhibition was observed after the first ravulizumab infusion and was sustained throughout the 26-week treatment period.

Safety

Dr Lee said ravulizumab had a similar safety profile to eculizumab, and both drugs were well tolerated.

Most patients experienced a treatment-emergent adverse event (TEAE)—88% in the ravulizumab arm and 86.8% in the eculizumab arm.

The most common TEAEs (in the ravulizumab and eculizumab arms, respectively) were headache (36.0% and 33.1%), nasopharyngitis (8.8% and 14.9%), upper respiratory tract infection (10.4% and 5.8%), and pyrexia (4.8% and 10.7%).

Serious AEs occurred in 8.8% of patients in the ravulizumab arm and 7.4% of those in the eculizumab arm.

Major adverse vascular events occurred in 2 patients in the ravulizumab arm and 1 in the eculizumab arm. There were no meningococcal infections in either arm.

One patient in the eculizumab arm was discontinued from the study and died of lung cancer (which was unrelated to treatment).

Photo from EHA

STOCKHOLM—Results of a phase 3 study suggest the long-acting C5 complement inhibitor ravulizumab produces similar results as eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Treatment with ravulizumab every 8 weeks proved noninferior to treatment with eculizumab every 2 weeks for the co-primary endpoints of transfusion avoidance and hemolysis as measured by lactate dehydrogenase (LDH) normalization.

Ravulizumab also proved noninferior with regard to secondary efficacy endpoints and had a safety profile similar to that of eculizumab.

These results suggest ravulizumab could be a more convenient alternative for PNH patients, according to Jong Wook Lee, MD, of Seoul St. Mary’s Hospital in Seoul, South Korea.

Dr Lee presented these results as a late-breaking abstract (LB2603) at the 23rd Congress of the European Hematology Association (EHA).

The study was sponsored by Alexion Pharmaceuticals.

The trial enrolled adults with PNH naive to complement inhibitor therapy. They were randomized to receive ravulizumab (n=125) or eculizumab (n=121) for 183 days.

More than half of patients were male—52% in the ravulizumab arm and 57% in the eculizumab arm.  Most patients were Asian (57.6% in the ravulizumab arm and 47.1% in the eculizumab arm) or white (34.4% and 42.1%, respectively).

Patients’ mean age at first infusion was 44.8 in the ravulizumab arm and 46.2 in the eculizumab arm. The mean number of years from PNH diagnosis to consent was 6.7 and 6.4, respectively.

The mean LDH at baseline was 1634 U/L in the ravulizumab arm and 1578 U/L in the eculizumab arm. The mean FACIT-Fatigue score was 36.7 and 36.9, respectively.

All 125 ravulizumab patients completed 26 weeks of treatment, as did 119 of the eculizumab patients. One hundred twenty-four ravulizumab patients entered the extension phase, as did 119 eculizumab patients.

Efficacy

The study’s primary efficacy endpoints were transfusion avoidance and LDH normalization from day 29 to 183. Dr Lee said ravulizumab proved noninferior to eculizumab for both endpoints, and point estimates favored ravulizumab.

The proportion of patients who remained transfusion-free was 73.6% in the ravulizumab arm and 66.1% in the eculizumab arm (difference, 6.8; 95% CI, -4.66, 18.14).

The proportion of patients who achieved LDH normalization was 53.6% and 49.4%, respectively (difference, 1.19; 95% CI, 0.8, 1.77).

Secondary efficacy endpoints included the percentage change in LDH from baseline, change in FACIT-Fatigue score from baseline, and the proportions of patients with breakthrough hemolysis and stabilized hemoglobin.

Again, ravulizumab was noninferior to eculizumab for all endpoints, with point estimates favoring ravulizumab.

The LDH percentage change was -76.84% in the ravulizumab arm and -76.02% in the eculizumab arm (difference, 0.83; 95% CI, -3.56, 5.21).

The change (improvement) in FACIT-Fatigue score was 7.07 and 6.40, respectively (difference, 0.67; 95% CI, -1.21, 2.55).

The percentage of patients with hemoglobin stabilization was 68.0% in the ravulizumab arm and 64.5% in the eculizumab arm (difference, 2.9; 95% CI, -8.80, 14.64).

The percentage of patients with breakthrough hemolysis was 4.0% and 10.7%, respectively (difference, 6.7; 95% CI, -0.18, 14.21).

Dr Lee noted that the proportion of patients with breakthrough hemolysis was more than 2.5-fold higher in the eculizumab arm than the ravulizumab arm—13 patients with 15 events and 5 patients with 5 events, respectively.

He said this was likely due to the immediate, complete, and sustained inhibition of C5 (mean free C5 <0.5 μg/mL) achieved by ravulizumab. Complete inhibition was observed after the first ravulizumab infusion and was sustained throughout the 26-week treatment period.

Safety

Dr Lee said ravulizumab had a similar safety profile to eculizumab, and both drugs were well tolerated.

Most patients experienced a treatment-emergent adverse event (TEAE)—88% in the ravulizumab arm and 86.8% in the eculizumab arm.

The most common TEAEs (in the ravulizumab and eculizumab arms, respectively) were headache (36.0% and 33.1%), nasopharyngitis (8.8% and 14.9%), upper respiratory tract infection (10.4% and 5.8%), and pyrexia (4.8% and 10.7%).

Serious AEs occurred in 8.8% of patients in the ravulizumab arm and 7.4% of those in the eculizumab arm.

Major adverse vascular events occurred in 2 patients in the ravulizumab arm and 1 in the eculizumab arm. There were no meningococcal infections in either arm.

One patient in the eculizumab arm was discontinued from the study and died of lung cancer (which was unrelated to treatment).

Photo from EHA

STOCKHOLM—Results of a phase 3 study suggest the long-acting C5 complement inhibitor ravulizumab produces similar results as eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Treatment with ravulizumab every 8 weeks proved noninferior to treatment with eculizumab every 2 weeks for the co-primary endpoints of transfusion avoidance and hemolysis as measured by lactate dehydrogenase (LDH) normalization.

Ravulizumab also proved noninferior with regard to secondary efficacy endpoints and had a safety profile similar to that of eculizumab.

These results suggest ravulizumab could be a more convenient alternative for PNH patients, according to Jong Wook Lee, MD, of Seoul St. Mary’s Hospital in Seoul, South Korea.

Dr Lee presented these results as a late-breaking abstract (LB2603) at the 23rd Congress of the European Hematology Association (EHA).

The study was sponsored by Alexion Pharmaceuticals.

The trial enrolled adults with PNH naive to complement inhibitor therapy. They were randomized to receive ravulizumab (n=125) or eculizumab (n=121) for 183 days.

More than half of patients were male—52% in the ravulizumab arm and 57% in the eculizumab arm.  Most patients were Asian (57.6% in the ravulizumab arm and 47.1% in the eculizumab arm) or white (34.4% and 42.1%, respectively).

Patients’ mean age at first infusion was 44.8 in the ravulizumab arm and 46.2 in the eculizumab arm. The mean number of years from PNH diagnosis to consent was 6.7 and 6.4, respectively.

The mean LDH at baseline was 1634 U/L in the ravulizumab arm and 1578 U/L in the eculizumab arm. The mean FACIT-Fatigue score was 36.7 and 36.9, respectively.

All 125 ravulizumab patients completed 26 weeks of treatment, as did 119 of the eculizumab patients. One hundred twenty-four ravulizumab patients entered the extension phase, as did 119 eculizumab patients.

Efficacy

The study’s primary efficacy endpoints were transfusion avoidance and LDH normalization from day 29 to 183. Dr Lee said ravulizumab proved noninferior to eculizumab for both endpoints, and point estimates favored ravulizumab.

The proportion of patients who remained transfusion-free was 73.6% in the ravulizumab arm and 66.1% in the eculizumab arm (difference, 6.8; 95% CI, -4.66, 18.14).

The proportion of patients who achieved LDH normalization was 53.6% and 49.4%, respectively (difference, 1.19; 95% CI, 0.8, 1.77).

Secondary efficacy endpoints included the percentage change in LDH from baseline, change in FACIT-Fatigue score from baseline, and the proportions of patients with breakthrough hemolysis and stabilized hemoglobin.

Again, ravulizumab was noninferior to eculizumab for all endpoints, with point estimates favoring ravulizumab.

The LDH percentage change was -76.84% in the ravulizumab arm and -76.02% in the eculizumab arm (difference, 0.83; 95% CI, -3.56, 5.21).

The change (improvement) in FACIT-Fatigue score was 7.07 and 6.40, respectively (difference, 0.67; 95% CI, -1.21, 2.55).

The percentage of patients with hemoglobin stabilization was 68.0% in the ravulizumab arm and 64.5% in the eculizumab arm (difference, 2.9; 95% CI, -8.80, 14.64).

The percentage of patients with breakthrough hemolysis was 4.0% and 10.7%, respectively (difference, 6.7; 95% CI, -0.18, 14.21).

Dr Lee noted that the proportion of patients with breakthrough hemolysis was more than 2.5-fold higher in the eculizumab arm than the ravulizumab arm—13 patients with 15 events and 5 patients with 5 events, respectively.

He said this was likely due to the immediate, complete, and sustained inhibition of C5 (mean free C5 <0.5 μg/mL) achieved by ravulizumab. Complete inhibition was observed after the first ravulizumab infusion and was sustained throughout the 26-week treatment period.

Safety

Dr Lee said ravulizumab had a similar safety profile to eculizumab, and both drugs were well tolerated.

Most patients experienced a treatment-emergent adverse event (TEAE)—88% in the ravulizumab arm and 86.8% in the eculizumab arm.

The most common TEAEs (in the ravulizumab and eculizumab arms, respectively) were headache (36.0% and 33.1%), nasopharyngitis (8.8% and 14.9%), upper respiratory tract infection (10.4% and 5.8%), and pyrexia (4.8% and 10.7%).

Serious AEs occurred in 8.8% of patients in the ravulizumab arm and 7.4% of those in the eculizumab arm.

Major adverse vascular events occurred in 2 patients in the ravulizumab arm and 1 in the eculizumab arm. There were no meningococcal infections in either arm.

One patient in the eculizumab arm was discontinued from the study and died of lung cancer (which was unrelated to treatment).

WASHINGTON – Three-quarters of patients with sickle cell disease (SCD) reported missing work in the last year because of disease symptoms, according to results from a single-center study.

While the direct costs of SCD are easy to measure, it’s harder to capture the indirect costs patients may incur from this chronic, progressive disease, which range from lost days at work to the downstream consequences of “presenteeism.”

“Indirect costs are related to things that have value, but it’s a little bit harder to apply an exact value to it,” said Nicholas Vendetti of Pfizer. But this is a critical piece for understanding SCD, he said. “The burden of illness is unknown without productivity costs.”

Mr. Vendetti and his collaborators attempted to capture the indirect costs of SCD, and reported the results of a single-site study at the annual meeting of the Foundation for Sickle Cell Disease Research.

They recruited patients from Virginia Commonwealth University’s adult sickle cell clinic and trained interviewers to conduct structured interviews using the Institute for Medical Technology Assessment Productivity Cost Questionnaire. The interviewers asked about absenteeism, lost work, unpaid work activity, and “presenteeism,” defined as days when participants were at work but experienced decreased work output because of disease symptoms.

In the end, the study enrolled 186 patients aged 18 and older, a figure that “really exceeded what we expected when we started the protocol,” Mr. Vendetti said. Most participants were between the ages of 20 and 60 years – the most productive working years.

About 58% of participants were female. Nearly half (46%) had the HbSS genotype, while 30% had the HbSC genotype. About half (52%) were high school graduates, and about a third had some college. There were no advanced degrees earned in the study population, and 11.5% had not finished high school.

Initial questions about educational status and employment status “highlighted a very interesting aspect of the disease: 43.8% reported that they were currently unable to work as part of their disease process,” Mr. Vendetti said. Just 28% were employed for wages, 3% were self-employed, and about 7% reported being homemakers. The remainder were out of work, were students, or were retired.

Three-quarters of patients reported missing work in the last year because of SCD symptoms. This group reported missing a mean 36.75 days yearly. Assuming the average Virginia hourly wage of $25.53 per hour, this comes to an average of $7,506 in lost wages each year, Mr. Vendetti said.

Presenteeism had a large impact as well. Nearly 73% of patients said they were bothered at work – either psychologically or physically – by their symptoms in the last 4 weeks, and 90% over the past year. These patients estimated they were affected for about 100 working days yearly.

When asked on a scale of 0-10 how much work they were able to get done on days when their SCD was affecting productivity, “most patients are falling into that middle range” of a score of 4-6, Mr. Vendetti said. “Most patients are moderately affected.

“It’s hard to apply a dollar value to that, but it’s easy to see how it could affect the trajectory of your career,” he added.

Another aspect of the indirect cost of the sickle cell disease burden that’s even harder to tease out is whether those affected are unable to complete a significant amount of unpaid work. Again, about three-quarters of patients reported that SCD had affected their ability to do this kind of work, and these patients said this happened on an average 105 days each year.

Even though patients may not be hiring others to do housework they’re unable to complete, or to care for children on days when they’re too unwell to do so, that doesn’t mean there’s no impact on the patient and those around them, Mr. Vendetti said. “If you ask a family member or a friend for help, that creates a strain in the relationship.”

In terms of resources to address the indirect burden of SCD on careers, Mr. Vendetti pointed out that many states have vocational rehabilitation programs that offer a significant amount of support and assistance to help find a productive work path that still accommodates a chronic illness such as SCD. In Virginia, he said, individuals need to be on disability to avail themselves of the program.

Health care providers can educate themselves about these and other programs. “Most adult sickle cell disease patients didn’t even know they might be eligible” for vocational assistance, he said.

During discussion after the presentation, an audience member pointed out that parents and caregivers of children with SCD are probably also incurring significant indirect costs because of their care-giving burden and that this population should also be studied. Mr. Vendetti agreed. “This is potential that isn’t fulfilled” for all patients and families whose work and personal lives are so profoundly affected by SCD, he said. “This is a dream deferred.”

Mr. Vendetti is employed by Pfizer and is a Pfizer stockholder. A coauthor of the study is a Pfizer consultant.

[email protected]

WASHINGTON – Three-quarters of patients with sickle cell disease (SCD) reported missing work in the last year because of disease symptoms, according to results from a single-center study.

While the direct costs of SCD are easy to measure, it’s harder to capture the indirect costs patients may incur from this chronic, progressive disease, which range from lost days at work to the downstream consequences of “presenteeism.”

“Indirect costs are related to things that have value, but it’s a little bit harder to apply an exact value to it,” said Nicholas Vendetti of Pfizer. But this is a critical piece for understanding SCD, he said. “The burden of illness is unknown without productivity costs.”

Mr. Vendetti and his collaborators attempted to capture the indirect costs of SCD, and reported the results of a single-site study at the annual meeting of the Foundation for Sickle Cell Disease Research.

They recruited patients from Virginia Commonwealth University’s adult sickle cell clinic and trained interviewers to conduct structured interviews using the Institute for Medical Technology Assessment Productivity Cost Questionnaire. The interviewers asked about absenteeism, lost work, unpaid work activity, and “presenteeism,” defined as days when participants were at work but experienced decreased work output because of disease symptoms.

In the end, the study enrolled 186 patients aged 18 and older, a figure that “really exceeded what we expected when we started the protocol,” Mr. Vendetti said. Most participants were between the ages of 20 and 60 years – the most productive working years.

About 58% of participants were female. Nearly half (46%) had the HbSS genotype, while 30% had the HbSC genotype. About half (52%) were high school graduates, and about a third had some college. There were no advanced degrees earned in the study population, and 11.5% had not finished high school.

Initial questions about educational status and employment status “highlighted a very interesting aspect of the disease: 43.8% reported that they were currently unable to work as part of their disease process,” Mr. Vendetti said. Just 28% were employed for wages, 3% were self-employed, and about 7% reported being homemakers. The remainder were out of work, were students, or were retired.

Three-quarters of patients reported missing work in the last year because of SCD symptoms. This group reported missing a mean 36.75 days yearly. Assuming the average Virginia hourly wage of $25.53 per hour, this comes to an average of $7,506 in lost wages each year, Mr. Vendetti said.

Presenteeism had a large impact as well. Nearly 73% of patients said they were bothered at work – either psychologically or physically – by their symptoms in the last 4 weeks, and 90% over the past year. These patients estimated they were affected for about 100 working days yearly.

When asked on a scale of 0-10 how much work they were able to get done on days when their SCD was affecting productivity, “most patients are falling into that middle range” of a score of 4-6, Mr. Vendetti said. “Most patients are moderately affected.

“It’s hard to apply a dollar value to that, but it’s easy to see how it could affect the trajectory of your career,” he added.

Another aspect of the indirect cost of the sickle cell disease burden that’s even harder to tease out is whether those affected are unable to complete a significant amount of unpaid work. Again, about three-quarters of patients reported that SCD had affected their ability to do this kind of work, and these patients said this happened on an average 105 days each year.

Even though patients may not be hiring others to do housework they’re unable to complete, or to care for children on days when they’re too unwell to do so, that doesn’t mean there’s no impact on the patient and those around them, Mr. Vendetti said. “If you ask a family member or a friend for help, that creates a strain in the relationship.”

In terms of resources to address the indirect burden of SCD on careers, Mr. Vendetti pointed out that many states have vocational rehabilitation programs that offer a significant amount of support and assistance to help find a productive work path that still accommodates a chronic illness such as SCD. In Virginia, he said, individuals need to be on disability to avail themselves of the program.

Health care providers can educate themselves about these and other programs. “Most adult sickle cell disease patients didn’t even know they might be eligible” for vocational assistance, he said.

During discussion after the presentation, an audience member pointed out that parents and caregivers of children with SCD are probably also incurring significant indirect costs because of their care-giving burden and that this population should also be studied. Mr. Vendetti agreed. “This is potential that isn’t fulfilled” for all patients and families whose work and personal lives are so profoundly affected by SCD, he said. “This is a dream deferred.”

Mr. Vendetti is employed by Pfizer and is a Pfizer stockholder. A coauthor of the study is a Pfizer consultant.

[email protected]

WASHINGTON – Three-quarters of patients with sickle cell disease (SCD) reported missing work in the last year because of disease symptoms, according to results from a single-center study.

While the direct costs of SCD are easy to measure, it’s harder to capture the indirect costs patients may incur from this chronic, progressive disease, which range from lost days at work to the downstream consequences of “presenteeism.”

“Indirect costs are related to things that have value, but it’s a little bit harder to apply an exact value to it,” said Nicholas Vendetti of Pfizer. But this is a critical piece for understanding SCD, he said. “The burden of illness is unknown without productivity costs.”

Mr. Vendetti and his collaborators attempted to capture the indirect costs of SCD, and reported the results of a single-site study at the annual meeting of the Foundation for Sickle Cell Disease Research.

They recruited patients from Virginia Commonwealth University’s adult sickle cell clinic and trained interviewers to conduct structured interviews using the Institute for Medical Technology Assessment Productivity Cost Questionnaire. The interviewers asked about absenteeism, lost work, unpaid work activity, and “presenteeism,” defined as days when participants were at work but experienced decreased work output because of disease symptoms.

In the end, the study enrolled 186 patients aged 18 and older, a figure that “really exceeded what we expected when we started the protocol,” Mr. Vendetti said. Most participants were between the ages of 20 and 60 years – the most productive working years.

About 58% of participants were female. Nearly half (46%) had the HbSS genotype, while 30% had the HbSC genotype. About half (52%) were high school graduates, and about a third had some college. There were no advanced degrees earned in the study population, and 11.5% had not finished high school.

Initial questions about educational status and employment status “highlighted a very interesting aspect of the disease: 43.8% reported that they were currently unable to work as part of their disease process,” Mr. Vendetti said. Just 28% were employed for wages, 3% were self-employed, and about 7% reported being homemakers. The remainder were out of work, were students, or were retired.

Three-quarters of patients reported missing work in the last year because of SCD symptoms. This group reported missing a mean 36.75 days yearly. Assuming the average Virginia hourly wage of $25.53 per hour, this comes to an average of $7,506 in lost wages each year, Mr. Vendetti said.

Presenteeism had a large impact as well. Nearly 73% of patients said they were bothered at work – either psychologically or physically – by their symptoms in the last 4 weeks, and 90% over the past year. These patients estimated they were affected for about 100 working days yearly.

When asked on a scale of 0-10 how much work they were able to get done on days when their SCD was affecting productivity, “most patients are falling into that middle range” of a score of 4-6, Mr. Vendetti said. “Most patients are moderately affected.

“It’s hard to apply a dollar value to that, but it’s easy to see how it could affect the trajectory of your career,” he added.

Another aspect of the indirect cost of the sickle cell disease burden that’s even harder to tease out is whether those affected are unable to complete a significant amount of unpaid work. Again, about three-quarters of patients reported that SCD had affected their ability to do this kind of work, and these patients said this happened on an average 105 days each year.

Even though patients may not be hiring others to do housework they’re unable to complete, or to care for children on days when they’re too unwell to do so, that doesn’t mean there’s no impact on the patient and those around them, Mr. Vendetti said. “If you ask a family member or a friend for help, that creates a strain in the relationship.”

In terms of resources to address the indirect burden of SCD on careers, Mr. Vendetti pointed out that many states have vocational rehabilitation programs that offer a significant amount of support and assistance to help find a productive work path that still accommodates a chronic illness such as SCD. In Virginia, he said, individuals need to be on disability to avail themselves of the program.

Health care providers can educate themselves about these and other programs. “Most adult sickle cell disease patients didn’t even know they might be eligible” for vocational assistance, he said.

During discussion after the presentation, an audience member pointed out that parents and caregivers of children with SCD are probably also incurring significant indirect costs because of their care-giving burden and that this population should also be studied. Mr. Vendetti agreed. “This is potential that isn’t fulfilled” for all patients and families whose work and personal lives are so profoundly affected by SCD, he said. “This is a dream deferred.”

Mr. Vendetti is employed by Pfizer and is a Pfizer stockholder. A coauthor of the study is a Pfizer consultant.

[email protected]

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

Red blood cells

Mircera®, methoxy polyethylene glycol-epoetin beta, was approved by the US Food and Drug Administration (FDA) to treat anemia in pediatric patients who have chronic kidney disease (CKD).

The drug is indicated for patients ages 5 to 17 years on hemodialysis who are switching from another erythropoiesis-stimulating agent (ESA) after their hemoglobin levels have stabilized.

The FDA also approved the agent to treat adult patients with CKD-associated anemia.

However, the drug is not approved to treat anemia caused by cancer chemotherapy.

The FDA based its approval on data from an open-label, multiple-dose, multicenter, dose-finding trial (NCT00717366).

Investigators enrolled 64 pediatric patients with CKD on hemodialysis. The patients had to have stable hemoglobin levels while receiving another ESA, such as epoetin alfa/beta or darbepoetin alfa.

Patients received Mircera intravenously once every 4 weeks for 20 weeks. Investigators adjusted the dosages, if necessary, after the first administration to maintain target hemoglobin levels.

Efficacy was based on the patients’ ability to maintain target hemoglobin levels and also on data extrapolated from trials of Mircera in adults with CKD.

Patients who received Mircera had a mean change in hemoglobin concentration from baseline of -0.15g/dL and 75% maintained hemoglobin values within ± 1g/dL of baseline.

Eighty-one percent maintained hemoglobin values within 10–12g/dL during the evaluation period.

The safety findings in pediatric patients were consistent with those previously reported in adults.

The most common adverse reactions occurring in 10% or more patients, as indicated in the prescribing information, are hypertension, diarrhea, and nasopharyngitis.

The drug carries a black box warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression of recurrence.

Mircera is an erythropoietin receptor activator with greater activity in vivo as well as increased half-life, compared to erythropoietin.

Mircera is manufactured by Vifor (International) Inc. 

Red blood cells

Mircera®, methoxy polyethylene glycol-epoetin beta, was approved by the US Food and Drug Administration (FDA) to treat anemia in pediatric patients who have chronic kidney disease (CKD).

The drug is indicated for patients ages 5 to 17 years on hemodialysis who are switching from another erythropoiesis-stimulating agent (ESA) after their hemoglobin levels have stabilized.

The FDA also approved the agent to treat adult patients with CKD-associated anemia.

However, the drug is not approved to treat anemia caused by cancer chemotherapy.

The FDA based its approval on data from an open-label, multiple-dose, multicenter, dose-finding trial (NCT00717366).

Investigators enrolled 64 pediatric patients with CKD on hemodialysis. The patients had to have stable hemoglobin levels while receiving another ESA, such as epoetin alfa/beta or darbepoetin alfa.

Patients received Mircera intravenously once every 4 weeks for 20 weeks. Investigators adjusted the dosages, if necessary, after the first administration to maintain target hemoglobin levels.

Efficacy was based on the patients’ ability to maintain target hemoglobin levels and also on data extrapolated from trials of Mircera in adults with CKD.

Patients who received Mircera had a mean change in hemoglobin concentration from baseline of -0.15g/dL and 75% maintained hemoglobin values within ± 1g/dL of baseline.

Eighty-one percent maintained hemoglobin values within 10–12g/dL during the evaluation period.

The safety findings in pediatric patients were consistent with those previously reported in adults.

The most common adverse reactions occurring in 10% or more patients, as indicated in the prescribing information, are hypertension, diarrhea, and nasopharyngitis.

The drug carries a black box warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression of recurrence.

Mircera is an erythropoietin receptor activator with greater activity in vivo as well as increased half-life, compared to erythropoietin.

Mircera is manufactured by Vifor (International) Inc. 

Red blood cells

Mircera®, methoxy polyethylene glycol-epoetin beta, was approved by the US Food and Drug Administration (FDA) to treat anemia in pediatric patients who have chronic kidney disease (CKD).

The drug is indicated for patients ages 5 to 17 years on hemodialysis who are switching from another erythropoiesis-stimulating agent (ESA) after their hemoglobin levels have stabilized.

The FDA also approved the agent to treat adult patients with CKD-associated anemia.

However, the drug is not approved to treat anemia caused by cancer chemotherapy.

The FDA based its approval on data from an open-label, multiple-dose, multicenter, dose-finding trial (NCT00717366).

Investigators enrolled 64 pediatric patients with CKD on hemodialysis. The patients had to have stable hemoglobin levels while receiving another ESA, such as epoetin alfa/beta or darbepoetin alfa.

Patients received Mircera intravenously once every 4 weeks for 20 weeks. Investigators adjusted the dosages, if necessary, after the first administration to maintain target hemoglobin levels.

Efficacy was based on the patients’ ability to maintain target hemoglobin levels and also on data extrapolated from trials of Mircera in adults with CKD.

Patients who received Mircera had a mean change in hemoglobin concentration from baseline of -0.15g/dL and 75% maintained hemoglobin values within ± 1g/dL of baseline.

Eighty-one percent maintained hemoglobin values within 10–12g/dL during the evaluation period.

The safety findings in pediatric patients were consistent with those previously reported in adults.

The most common adverse reactions occurring in 10% or more patients, as indicated in the prescribing information, are hypertension, diarrhea, and nasopharyngitis.

The drug carries a black box warning for increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression of recurrence.

Mircera is an erythropoietin receptor activator with greater activity in vivo as well as increased half-life, compared to erythropoietin.

Mircera is manufactured by Vifor (International) Inc. 

The Food and Drug Administration has approved methoxy polyethylene glycol-epoetin beta (Mircera) for the treatment of dialysis-related anemia in pediatric patients aged 5-17 years with chronic kidney disease whose hemoglobin had been stabilized with an erythropoiesis-stimulating agent (ESA).

[email protected]

The Food and Drug Administration has approved methoxy polyethylene glycol-epoetin beta (Mircera) for the treatment of dialysis-related anemia in pediatric patients aged 5-17 years with chronic kidney disease whose hemoglobin had been stabilized with an erythropoiesis-stimulating agent (ESA).

[email protected]

The Food and Drug Administration has approved methoxy polyethylene glycol-epoetin beta (Mircera) for the treatment of dialysis-related anemia in pediatric patients aged 5-17 years with chronic kidney disease whose hemoglobin had been stabilized with an erythropoiesis-stimulating agent (ESA).

[email protected]

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Vials and a syringe

The US Food and Drug Association (FDA) has approved pegfilgrastim-jmdb (Fulphila™) as the first biosimilar to Neulasta®.

The agents reduce the risk of infection or the duration of febrile neutropenia in patients treated with immunosuppressive chemotherapy for non-myeloid hematologic malignancies.

The FDA approved Fulphila based on evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

The evidence demonstrated that Fulphila is biosimilar to Amgen’s Neulasta. The FDA, in its announcement, noted that Fulphila has been approved as a biosimilar and not as an interchangeable product.

A biosimilar is a biological product approved based on data showing it is highly similar to a biological product already approved by the FDA, termed the reference product.

A biosimilar has no clinically meaningful differences from the reference product in terms of safety, purity, and effectiveness.

Common side effects of Fulphila include bone pain and pain in extremities.

The FDA cautions that patients with a history of serious allergic reaction to human granulocyte colony-stimulating factors, such as pegfilgrastim or filgrastim products, should not take Fulphila.

Serious side effects from Fulphila include:

• rupture of the spleen
• acute respiratory distress syndrome
• serious allergic reactions including anaphylaxis
• glomerulonephritis
• leukocytosis
• capillary leak syndrome
• potential for tumor growth

Fatal sickle cell crises have also occurred with Fulphila use.

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

The FDA is planning to release a comprehensive new plan to advance policy efforts that promote biosimilar product development, according to FDA Commissioner Scott Gotlieb, MD.

“We want to make sure that the pathway for developing biosimilar versions of approved biologics is efficient and effective, so that patients benefit from competition to existing biologics once lawful intellectual property has lapsed on these products,” he said in the announcement.

The FDA granted approval of Fulphila to Mylan GmbH. Mylan is co-developing Fulphila with Biocon.

Last fall, the agency had issued a complete response letter saying it could not approve the proposed biosimilar pending an update to the application.

The complete response letter did not raise any questions on the biosimilarity of Fulphila (investigational drug product MYL-1401H), pharmacokinetic/pharmacodynamic data, clinical data, or immunogenicity, however.

Mylan anticipates launching Fulphila in the coming weeks. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

Image by Betty Pace

The US Food and Drug Administration (FDA) has placed a clinical hold on the investigational new drug application (IND) for CTX001. The agent is being developed for the treatment of sickle cell disease (SCD) and β-thalassemia.

The IND was submitted to the FDA in April to support the initiation of a phase 1/2 trial in the US in adult patients with SCD. The hold will be in place pending the resolution of questions as part of the FDA review.

The phase 1/2 trial in Europe in adult patients with transfusion-dependent β-thalassemia is expected to proceed according to schedule. Trial initiation is planned for the second half of 2018.

CTX001 is being co-developed and co-commercialized by CRISPR Therapeutics and Vertex Pharmaceuticals Incorporated.

The agent is an investigational ex vivo CRISPR gene edited therapy for patients with β-thalassemia or sickle cell disease.

The patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells.

The increase in HbF levels by CTX001 may potentially alleviate transfusion requirements for β-thalassemia patients and sickle crises for SCD patients. 

Image by Betty Pace

The US Food and Drug Administration (FDA) has placed a clinical hold on the investigational new drug application (IND) for CTX001. The agent is being developed for the treatment of sickle cell disease (SCD) and β-thalassemia.

The IND was submitted to the FDA in April to support the initiation of a phase 1/2 trial in the US in adult patients with SCD. The hold will be in place pending the resolution of questions as part of the FDA review.

The phase 1/2 trial in Europe in adult patients with transfusion-dependent β-thalassemia is expected to proceed according to schedule. Trial initiation is planned for the second half of 2018.

CTX001 is being co-developed and co-commercialized by CRISPR Therapeutics and Vertex Pharmaceuticals Incorporated.

The agent is an investigational ex vivo CRISPR gene edited therapy for patients with β-thalassemia or sickle cell disease.

The patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells.

The increase in HbF levels by CTX001 may potentially alleviate transfusion requirements for β-thalassemia patients and sickle crises for SCD patients. 

Image by Betty Pace

The US Food and Drug Administration (FDA) has placed a clinical hold on the investigational new drug application (IND) for CTX001. The agent is being developed for the treatment of sickle cell disease (SCD) and β-thalassemia.

The IND was submitted to the FDA in April to support the initiation of a phase 1/2 trial in the US in adult patients with SCD. The hold will be in place pending the resolution of questions as part of the FDA review.

The phase 1/2 trial in Europe in adult patients with transfusion-dependent β-thalassemia is expected to proceed according to schedule. Trial initiation is planned for the second half of 2018.

CTX001 is being co-developed and co-commercialized by CRISPR Therapeutics and Vertex Pharmaceuticals Incorporated.

The agent is an investigational ex vivo CRISPR gene edited therapy for patients with β-thalassemia or sickle cell disease.

The patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells.

The increase in HbF levels by CTX001 may potentially alleviate transfusion requirements for β-thalassemia patients and sickle crises for SCD patients.