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CAR T-cell therapy shows early promise in DLBCL
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy. 
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.
LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.
In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.
At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.
“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.
He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.
Patients
Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.
The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.
Treatment
Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.
Thirty patients received a single dose of JCAR017 at 5 x 107 CAR cells (dose-level 1, single [DL1S]).
Six patients received 2 doses of 5 x 107 CAR cells (dose-level 1, double [DL1D]).
Nineteen patients received a single dose of 1 x 108 CAR cells (dose-level 2, single [DL2S]).
Safety
More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.
Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.
One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.
Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.
The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).
There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).
“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.
Response
Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.
Dr Abramson noted that there was a dose-response relationship.
Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.
At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.
Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.
At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.
SCD therapy granted access to PRIME program
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
The European Medicines Agency (EMA) has granted GBT440 access to the agency’s PRIority MEdicines (PRIME) program.
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for sickle cell disease (SCD).
GBT440 works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
About PRIME
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
Phase 1/2 trial
The GBT440 acceptance in the PRIME program was supported by data from an ongoing phase 1/2 trial (GBT440-001) in which researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of GBT440 in healthy subjects and adults with SCD.
Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
EC grants factor IX therapy orphan designation
The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.
CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.
The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.
Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.
Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.
CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.
The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.
Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.
Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.
CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.
The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.
Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.
Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
T-cell product improves outcomes of haplo-HSCT
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).
In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.
Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.
“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.
Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.
The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.
About BPX-501
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.
Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.
The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.
Patients
Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.
Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).
Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).
The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.
Overall results
Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.
At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.
The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.
Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.
There were no adverse events associated with BPX-501 or rimiducid.
European cohort
Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.
Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.
Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).
Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).
The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).
The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.
There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.
“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”
Single-dose NEPA found non-inferior to aprepitant/granisetron
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
Lower dose of rivaroxaban receives priority review
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).
The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.
The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.
During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.
Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.
The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.
The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.
The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).
The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.
The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.
During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.
Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.
The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.
The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.
The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).
The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.
The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.
During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.
Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.
The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.
The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.
The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.
Less is more in PET-negative, advanced HL
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
CSF p-Tau predicts neurocognitive sequelae in survivors of childhood cancer
A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.
Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.
They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”
The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.
All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.
"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."
Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.
Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor. Parental socioeconomic status was a covariate.
Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.
Findings
Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.
They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.
Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).
And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.
Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).
However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).
The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.
For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.
But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.
Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.
Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.
"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."
The Olivia Hendrickx Research Fund supported the study.
A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.
Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.
They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”
The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.
All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.
"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."
Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.
Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor. Parental socioeconomic status was a covariate.
Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.
Findings
Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.
They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.
Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).
And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.
Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).
However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).
The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.
For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.
But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.
Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.
Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.
"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."
The Olivia Hendrickx Research Fund supported the study.
A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.
Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.
They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”
The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.
All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.
"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."
Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.
Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor. Parental socioeconomic status was a covariate.
Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.
Findings
Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.
They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.
Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).
And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.
Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).
However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).
The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.
For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.
But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.
Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.
Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.
"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."
The Olivia Hendrickx Research Fund supported the study.
Brentuximab meets phase 3 primary endpoint in frontline advanced HL
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
Betrixaban receives FDA approval for VTE prophylaxis in adults
The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.
Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.
Betrixaban had also received fast track designation from the FDA.
Betrixaban is Portola’s first commercial product.
The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.
The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.
Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.
Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.
Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.
Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).
The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.
Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.
The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).
The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.
The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.
Portola expects to launch betrixaban between August and November 2017.
The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.
Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.
Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.
Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.
See the full prescribing information for more details on betrixaban.
The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.
Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.
Betrixaban had also received fast track designation from the FDA.
Betrixaban is Portola’s first commercial product.
The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.
The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.
Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.
Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.
Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.
Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).
The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.
Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.
The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).
The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.
The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.
Portola expects to launch betrixaban between August and November 2017.
The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.
Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.
Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.
Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.
See the full prescribing information for more details on betrixaban.
The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.
Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.
Betrixaban had also received fast track designation from the FDA.
Betrixaban is Portola’s first commercial product.
The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.
The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.
Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.
Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.
Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.
Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).
The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.
Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.
The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).
The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.
The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.
Portola expects to launch betrixaban between August and November 2017.
The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.
Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.
Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.
Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.
See the full prescribing information for more details on betrixaban.