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Studies of donor CAR T cells placed on hold
The US Food and Drug Administration (FDA) has placed a clinical hold on both phase 1 studies of UCART123, a universal (allogeneic) chimeric antigen receptor (CAR) T-cell therapy targeting CD123.
One study was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
The clinical hold is due to the death of the first patient treated in the BPDCN trial.
The hold means no new subjects can be enrolled in either trial, and there can be no further dosing of subjects who are already enrolled.
BPDCN patient
The first patient treated in the BPDCN trial was a 78-year-old male who had received 1 prior therapy. He presented with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions (biopsy-proven BPDCN) at baseline.
The patient first received pre-conditioning with fludarabine (30 mg/m²/day for 4 days) and cyclophosphamide (1 g/m²/day for 3 days).
On August 16, 2017 (Day 0), the patient received UCART123 at 6.25 x 105 cells/kg, the first dose level explored in the protocol, without complication.
By Day 5, the patient had developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection, which improved after a first dose of tocilizumab and the administration of broad-spectrum, intravenous antibiotics.
On Day 8, the patient was found to have more severe CRS (ultimately grade 5) and grade 4 capillary leak syndrome. Despite receiving treatment in keeping with CRS management, including the administration of corticosteroids and tociluzumab as well as intensive care unit support, the patient died on Day 9.
AML patient
The first patient treated in the AML study experienced similar adverse effects as the BPDCN patient but is still alive.
The AML patient was a 58-year-old woman with 84% blasts in her bone marrow at baseline.
On June 27, 2017 (Day 0), the patient received the same pre-conditioning regimen and the same dose of UCART123 as the BPDCN patient, without complication.
By Day 8, the AML patient had developed grade 2 CRS. This worsened to grade 3 on Day 9 and resolved on Day 11 with treatment in the intensive care unit.
The patient also experienced grade 4 capillary leak syndrome on Day 9 that resolved on Day 12.
Next steps
The data safety monitoring board for these trials met on August 28 and recommended lowering the dose of UCART123 to 6.25 x 104 cells/kg in both studies and capping cyclophosphamide to a total dose of 4 g over 3 days.
Cellectis, the company developing UCART123, said it is working with study investigators and the FDA to resume both trials with an amended protocol that includes these dose adjustments. 
The US Food and Drug Administration (FDA) has placed a clinical hold on both phase 1 studies of UCART123, a universal (allogeneic) chimeric antigen receptor (CAR) T-cell therapy targeting CD123.
One study was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
The clinical hold is due to the death of the first patient treated in the BPDCN trial.
The hold means no new subjects can be enrolled in either trial, and there can be no further dosing of subjects who are already enrolled.
BPDCN patient
The first patient treated in the BPDCN trial was a 78-year-old male who had received 1 prior therapy. He presented with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions (biopsy-proven BPDCN) at baseline.
The patient first received pre-conditioning with fludarabine (30 mg/m²/day for 4 days) and cyclophosphamide (1 g/m²/day for 3 days).
On August 16, 2017 (Day 0), the patient received UCART123 at 6.25 x 105 cells/kg, the first dose level explored in the protocol, without complication.
By Day 5, the patient had developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection, which improved after a first dose of tocilizumab and the administration of broad-spectrum, intravenous antibiotics.
On Day 8, the patient was found to have more severe CRS (ultimately grade 5) and grade 4 capillary leak syndrome. Despite receiving treatment in keeping with CRS management, including the administration of corticosteroids and tociluzumab as well as intensive care unit support, the patient died on Day 9.
AML patient
The first patient treated in the AML study experienced similar adverse effects as the BPDCN patient but is still alive.
The AML patient was a 58-year-old woman with 84% blasts in her bone marrow at baseline.
On June 27, 2017 (Day 0), the patient received the same pre-conditioning regimen and the same dose of UCART123 as the BPDCN patient, without complication.
By Day 8, the AML patient had developed grade 2 CRS. This worsened to grade 3 on Day 9 and resolved on Day 11 with treatment in the intensive care unit.
The patient also experienced grade 4 capillary leak syndrome on Day 9 that resolved on Day 12.
Next steps
The data safety monitoring board for these trials met on August 28 and recommended lowering the dose of UCART123 to 6.25 x 104 cells/kg in both studies and capping cyclophosphamide to a total dose of 4 g over 3 days.
Cellectis, the company developing UCART123, said it is working with study investigators and the FDA to resume both trials with an amended protocol that includes these dose adjustments.
The US Food and Drug Administration (FDA) has placed a clinical hold on both phase 1 studies of UCART123, a universal (allogeneic) chimeric antigen receptor (CAR) T-cell therapy targeting CD123.
One study was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
The clinical hold is due to the death of the first patient treated in the BPDCN trial.
The hold means no new subjects can be enrolled in either trial, and there can be no further dosing of subjects who are already enrolled.
BPDCN patient
The first patient treated in the BPDCN trial was a 78-year-old male who had received 1 prior therapy. He presented with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions (biopsy-proven BPDCN) at baseline.
The patient first received pre-conditioning with fludarabine (30 mg/m²/day for 4 days) and cyclophosphamide (1 g/m²/day for 3 days).
On August 16, 2017 (Day 0), the patient received UCART123 at 6.25 x 105 cells/kg, the first dose level explored in the protocol, without complication.
By Day 5, the patient had developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection, which improved after a first dose of tocilizumab and the administration of broad-spectrum, intravenous antibiotics.
On Day 8, the patient was found to have more severe CRS (ultimately grade 5) and grade 4 capillary leak syndrome. Despite receiving treatment in keeping with CRS management, including the administration of corticosteroids and tociluzumab as well as intensive care unit support, the patient died on Day 9.
AML patient
The first patient treated in the AML study experienced similar adverse effects as the BPDCN patient but is still alive.
The AML patient was a 58-year-old woman with 84% blasts in her bone marrow at baseline.
On June 27, 2017 (Day 0), the patient received the same pre-conditioning regimen and the same dose of UCART123 as the BPDCN patient, without complication.
By Day 8, the AML patient had developed grade 2 CRS. This worsened to grade 3 on Day 9 and resolved on Day 11 with treatment in the intensive care unit.
The patient also experienced grade 4 capillary leak syndrome on Day 9 that resolved on Day 12.
Next steps
The data safety monitoring board for these trials met on August 28 and recommended lowering the dose of UCART123 to 6.25 x 104 cells/kg in both studies and capping cyclophosphamide to a total dose of 4 g over 3 days.
Cellectis, the company developing UCART123, said it is working with study investigators and the FDA to resume both trials with an amended protocol that includes these dose adjustments.
FDA grants orphan designation to product for CMV
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
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.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
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.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
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.
SCD drug receives rare pediatric disease designation
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
FDA grants orphan designation to product for GVHD
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
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.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
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.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
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.
Study confirms zoonotic transmission of malaria
Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.
Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.
The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.
Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.
This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.
In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.
P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.
All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.
“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.
“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”
Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.
“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.
“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”
Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.
Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.
The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.
Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.
This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.
In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.
P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.
All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.
“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.
“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”
Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.
“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.
“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”
Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.
Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.
The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.
Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.
This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.
In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.
P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.
All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.
“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.
“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”
Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.
“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.
“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”
Team creates rainbow of fluorescent dyes
Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.
The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.
Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.
Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.
The team detailed their work in Nature Methods.
Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.
“Now, we’ve figured out the rules, and we can make almost any color,” he said.
Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.
Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.
That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.
Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.
In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.
Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.
The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.
Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”
The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.
Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.
The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.
Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.
Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.
The team detailed their work in Nature Methods.
Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.
“Now, we’ve figured out the rules, and we can make almost any color,” he said.
Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.
Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.
That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.
Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.
In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.
Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.
The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.
Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”
The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.
Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.
The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.
Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.
Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.
The team detailed their work in Nature Methods.
Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.
“Now, we’ve figured out the rules, and we can make almost any color,” he said.
Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.
Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.
That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.
Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.
In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.
Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.
The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.
Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”
The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.
Paper-based diagnostic device is like ‘portable lab’
Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.
The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.
The devices produce color-coded test results that are easy for non-experts to understand.
“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.
“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”
Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.
SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.
The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.
The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.
The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.
An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.
“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.
SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.
Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.
The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.
Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.
The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.
The devices produce color-coded test results that are easy for non-experts to understand.
“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.
“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”
Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.
SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.
The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.
The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.
The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.
An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.
“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.
SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.
Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.
The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.
Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.
The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.
The devices produce color-coded test results that are easy for non-experts to understand.
“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.
“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”
Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.
SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.
The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.
The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.
The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.
An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.
“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.
SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.
Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.
The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.
Withdrawn AML drug back on market in US
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
Nanocarriers could treat leukemia, lymphoma and improve HSCT
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Young cancer patients want more digital support, survey says
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.