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Assay intended to aid PV diagnosis cleared for use in US
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area. 
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area.
The US Food and Drug Administration has granted 510(k) clearance for QIAGEN’s ipsogen® JAK2 RGQ PCR Kit (ipsogen JAK2 assay), and the company has launched the assay in the US.
The ipsogen JAK2 assay is designed to detect the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood.
The assay is intended for use in conjunction with other clinicopathological factors to aid the diagnosis of polycythemia vera (PV).
The test does not detect less common mutations associated with PV, including mutations in exon 12, and is not intended for stand-alone diagnosis of PV.
The ipsogen JAK2 assay is a real-time polymerase chain reaction test performed on the QIAGEN Rotor-Gene Q MDx instrument.
Researchers evaluated the utility of the ipsogen JAK2 assay for PV diagnosis in a prospective trial enrolling more than 200 subjects.
Data from this trial have not been published. However, according to QIAGEN, the assay provided 94.6% sensitivity and 98.1% specificity, together with a 100% positive percentage agreement and a 99.4% negative percentage agreement to bi-directional sequencing.
QIAGEN said these results suggest the ipsogen JAK2 assay enables detection of PV in the majority of subjects with the disease and helps rule out PV in the majority of individuals without it.
“We are pleased to be able to offer our ipsogen JAK2 assay, which is already available in Europe and other markets, for use in the United States and make it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for suspected PV patients,” said Thierry Bernard, senior vice president and head of QIAGEN’s Molecular Diagnostics Business Area.
Drug granted fast track designation for PNH
The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.
Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.
The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.
Coversin is being developed by Akari Therapeutics.
Akari is evaluating Coversin in a pair of phase 2 trials.
In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.
In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.
One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.
About fast track designation
The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.
Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.
Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.
Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.
The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.
Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.
The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.
Coversin is being developed by Akari Therapeutics.
Akari is evaluating Coversin in a pair of phase 2 trials.
In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.
In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.
One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.
About fast track designation
The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.
Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.
Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.
Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.
The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.
Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.
The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.
Coversin is being developed by Akari Therapeutics.
Akari is evaluating Coversin in a pair of phase 2 trials.
In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.
In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.
One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.
About fast track designation
The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.
Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.
Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.
Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.
Immunotherapy exhibits antileukemic activity in high-risk patients
Blinatumomab has demonstrated activity in high-risk patients with Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to research published in the Journal of Clinical Oncology.
This phase 2 trial enrolled patients with relapsed or refractory Ph+ BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
Blinatumomab produced a complete response (CR) in 31% of these patients, the median relapse-free survival was 6.7 months, and the median overall survival was 7.1 months.
The most common adverse events (AEs) were pyrexia, neurologic events, febrile neutropenia, and headache.
“Patients with Ph+ relapsed or refractory B-cell precursor ALL typically have lower remission rates, poor long-term prognosis, and shorter duration of remission than patients with Philadelphia chromosome-negative disease, and are especially in need of new treatment options beyond TKIs,” said study author Anthony Stein, MD, of City of Hope in Duarte, California.
“Results from this phase 2 study showed blinatumomab induced complete remission in these high-risk patients, regardless of prior TKI therapy or mutational status . . . .”
This study was supported by Amgen, the company developing and marketing blinatumomab.
The trial enrolled 45 patients with relapsed or refractory Ph+ BCP-ALL. Fifty-nine percent of patients had additional cytogenetic abnormalities. Forty-six percent had ABL1 kinase domain mutations, and 27% had the T315I mutation.
The patients’ median age was 55 (range, 23-78), and 55% were male. The median baseline bone marrow blast percentage was 80% (range, 6% to 98%).
Eighty-four percent of patients had received at least 2 prior TKIs. All patients were refractory to (56%), had relapsed on (33%), or progressed after (11%) TKI therapy. Forty-four percent of patients had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT).
The patients received blinatumomab in 28-day cycles by continuous intravenous infusion. The median number of cycles received was 2 (range, 1-5).
Efficacy
Thirty-six percent of patients (n=16) had a CR or CR with partial hematologic recovery (CRh) during the first 2 cycles of treatment. For 31% of patients (n=14), their best response was a CR.
Eighty-eight percent of patients who achieved a CR/CRh (n=14) achieved minimal residual disease (MRD) negativity.
Forty percent of patients with a T315I mutation had a CR/CRh (4/10), and all of these responders were MRD negative.
Seven responders (44%) went on to allo-HSCT, 6 of whom were transplant-naïve.
Eight of the 16 responders (50%) ultimately relapsed. Their median time to relapse was 6.7 months. Three patients relapsed during treatment, 2 relapsed without undergoing allo-HSCT, and 3 relapsed after allo-HSCT.
Seven responders (44%) were still alive and had not relapsed at last follow-up. The remaining responder died in CR after allo-HSCT.
The median relapse-free survival was 6.7 months, with or without censoring for allo-HSCT. And the median overall survival was 7.1 months, with or without censoring for allo-HSCT.
Safety
The most common AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Nearly half of patients (47%) had neurologic events.
Eighty-two percent of patients had grade 3 or higher treatment-emergent AEs. The most common were febrile neutropenia (27%), thrombocytopenia (22%), and anemia (16%).
Forty-four percent of patients had grade 3 or higher AEs that were considered possibly related to blinatumomab. The most common were febrile neutropenia and increased levels of alanine aminotransferase (11% each).
Five patients had fatal AEs—multiorgan failure, sepsis, septic shock, cerebral hemorrhage, and respiratory failure. The case of septic shock was considered related to treatment with blinatumomab.
Three patients developed cytokine release syndrome (all grade 1 or 2), but none of them had their treatment interrupted or discontinued as a result.
Three patients had grade 3 neurologic events, and 1 of these events (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events.
Blinatumomab has demonstrated activity in high-risk patients with Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to research published in the Journal of Clinical Oncology.
This phase 2 trial enrolled patients with relapsed or refractory Ph+ BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
Blinatumomab produced a complete response (CR) in 31% of these patients, the median relapse-free survival was 6.7 months, and the median overall survival was 7.1 months.
The most common adverse events (AEs) were pyrexia, neurologic events, febrile neutropenia, and headache.
“Patients with Ph+ relapsed or refractory B-cell precursor ALL typically have lower remission rates, poor long-term prognosis, and shorter duration of remission than patients with Philadelphia chromosome-negative disease, and are especially in need of new treatment options beyond TKIs,” said study author Anthony Stein, MD, of City of Hope in Duarte, California.
“Results from this phase 2 study showed blinatumomab induced complete remission in these high-risk patients, regardless of prior TKI therapy or mutational status . . . .”
This study was supported by Amgen, the company developing and marketing blinatumomab.
The trial enrolled 45 patients with relapsed or refractory Ph+ BCP-ALL. Fifty-nine percent of patients had additional cytogenetic abnormalities. Forty-six percent had ABL1 kinase domain mutations, and 27% had the T315I mutation.
The patients’ median age was 55 (range, 23-78), and 55% were male. The median baseline bone marrow blast percentage was 80% (range, 6% to 98%).
Eighty-four percent of patients had received at least 2 prior TKIs. All patients were refractory to (56%), had relapsed on (33%), or progressed after (11%) TKI therapy. Forty-four percent of patients had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT).
The patients received blinatumomab in 28-day cycles by continuous intravenous infusion. The median number of cycles received was 2 (range, 1-5).
Efficacy
Thirty-six percent of patients (n=16) had a CR or CR with partial hematologic recovery (CRh) during the first 2 cycles of treatment. For 31% of patients (n=14), their best response was a CR.
Eighty-eight percent of patients who achieved a CR/CRh (n=14) achieved minimal residual disease (MRD) negativity.
Forty percent of patients with a T315I mutation had a CR/CRh (4/10), and all of these responders were MRD negative.
Seven responders (44%) went on to allo-HSCT, 6 of whom were transplant-naïve.
Eight of the 16 responders (50%) ultimately relapsed. Their median time to relapse was 6.7 months. Three patients relapsed during treatment, 2 relapsed without undergoing allo-HSCT, and 3 relapsed after allo-HSCT.
Seven responders (44%) were still alive and had not relapsed at last follow-up. The remaining responder died in CR after allo-HSCT.
The median relapse-free survival was 6.7 months, with or without censoring for allo-HSCT. And the median overall survival was 7.1 months, with or without censoring for allo-HSCT.
Safety
The most common AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Nearly half of patients (47%) had neurologic events.
Eighty-two percent of patients had grade 3 or higher treatment-emergent AEs. The most common were febrile neutropenia (27%), thrombocytopenia (22%), and anemia (16%).
Forty-four percent of patients had grade 3 or higher AEs that were considered possibly related to blinatumomab. The most common were febrile neutropenia and increased levels of alanine aminotransferase (11% each).
Five patients had fatal AEs—multiorgan failure, sepsis, septic shock, cerebral hemorrhage, and respiratory failure. The case of septic shock was considered related to treatment with blinatumomab.
Three patients developed cytokine release syndrome (all grade 1 or 2), but none of them had their treatment interrupted or discontinued as a result.
Three patients had grade 3 neurologic events, and 1 of these events (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events.
Blinatumomab has demonstrated activity in high-risk patients with Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (BCP-ALL), according to research published in the Journal of Clinical Oncology.
This phase 2 trial enrolled patients with relapsed or refractory Ph+ BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
Blinatumomab produced a complete response (CR) in 31% of these patients, the median relapse-free survival was 6.7 months, and the median overall survival was 7.1 months.
The most common adverse events (AEs) were pyrexia, neurologic events, febrile neutropenia, and headache.
“Patients with Ph+ relapsed or refractory B-cell precursor ALL typically have lower remission rates, poor long-term prognosis, and shorter duration of remission than patients with Philadelphia chromosome-negative disease, and are especially in need of new treatment options beyond TKIs,” said study author Anthony Stein, MD, of City of Hope in Duarte, California.
“Results from this phase 2 study showed blinatumomab induced complete remission in these high-risk patients, regardless of prior TKI therapy or mutational status . . . .”
This study was supported by Amgen, the company developing and marketing blinatumomab.
The trial enrolled 45 patients with relapsed or refractory Ph+ BCP-ALL. Fifty-nine percent of patients had additional cytogenetic abnormalities. Forty-six percent had ABL1 kinase domain mutations, and 27% had the T315I mutation.
The patients’ median age was 55 (range, 23-78), and 55% were male. The median baseline bone marrow blast percentage was 80% (range, 6% to 98%).
Eighty-four percent of patients had received at least 2 prior TKIs. All patients were refractory to (56%), had relapsed on (33%), or progressed after (11%) TKI therapy. Forty-four percent of patients had undergone an allogeneic hematopoietic stem cell transplant (allo-HSCT).
The patients received blinatumomab in 28-day cycles by continuous intravenous infusion. The median number of cycles received was 2 (range, 1-5).
Efficacy
Thirty-six percent of patients (n=16) had a CR or CR with partial hematologic recovery (CRh) during the first 2 cycles of treatment. For 31% of patients (n=14), their best response was a CR.
Eighty-eight percent of patients who achieved a CR/CRh (n=14) achieved minimal residual disease (MRD) negativity.
Forty percent of patients with a T315I mutation had a CR/CRh (4/10), and all of these responders were MRD negative.
Seven responders (44%) went on to allo-HSCT, 6 of whom were transplant-naïve.
Eight of the 16 responders (50%) ultimately relapsed. Their median time to relapse was 6.7 months. Three patients relapsed during treatment, 2 relapsed without undergoing allo-HSCT, and 3 relapsed after allo-HSCT.
Seven responders (44%) were still alive and had not relapsed at last follow-up. The remaining responder died in CR after allo-HSCT.
The median relapse-free survival was 6.7 months, with or without censoring for allo-HSCT. And the median overall survival was 7.1 months, with or without censoring for allo-HSCT.
Safety
The most common AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Nearly half of patients (47%) had neurologic events.
Eighty-two percent of patients had grade 3 or higher treatment-emergent AEs. The most common were febrile neutropenia (27%), thrombocytopenia (22%), and anemia (16%).
Forty-four percent of patients had grade 3 or higher AEs that were considered possibly related to blinatumomab. The most common were febrile neutropenia and increased levels of alanine aminotransferase (11% each).
Five patients had fatal AEs—multiorgan failure, sepsis, septic shock, cerebral hemorrhage, and respiratory failure. The case of septic shock was considered related to treatment with blinatumomab.
Three patients developed cytokine release syndrome (all grade 1 or 2), but none of them had their treatment interrupted or discontinued as a result.
Three patients had grade 3 neurologic events, and 1 of these events (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events.
FDA lifts partial clinical hold for some selinexor trials
The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.
The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.
The hold meant that no new patients could be enrolled in selinexor trials.
Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.
Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.
In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.
“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.
“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”
About selinexor
Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor.
The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL).
The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.
The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.
The hold meant that no new patients could be enrolled in selinexor trials.
Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.
Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.
In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.
“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.
“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”
About selinexor
Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor.
The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL).
The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.
The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.
The hold meant that no new patients could be enrolled in selinexor trials.
Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.
Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.
In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.
“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.
“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”
About selinexor
Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).
This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor.
The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL).
Phase 2 study of daratumumab in NHL won’t proceed
The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.
In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).
Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.
The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.
Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.
The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.
“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.
In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.
Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab. 
The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.
In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).
Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.
The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.
Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.
The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.
“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.
In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.
Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.
The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.
In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).
Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.
The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.
Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.
The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.
“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.
In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.
Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.
FDA grants priority review to sBLA for blinatumomab
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).
The aim of this application is to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s current accelerated approval to a full approval.
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 Prescription Drug User Fee Act target action date for the blinatumomab sBLA is August 14, 2017.
About blinatumomab
Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
Blinatumomab currently has accelerated approval in the US as a treatment for adult and pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.
The FDA-approved prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities.
Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.
Blinatumomab is being developed and marketed by Amgen.
About the sBLA
With this sBLA, Amgen is seeking to make blinatumomab available as a treatment for patients with Philadelphia chromosome-positive (Ph+) relapsed/refractory BCP-ALL (as well as Ph-).
To this end, the application includes data from the ALCANTARA study, which were just published in the Journal of Clinical Oncology.
In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.
Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease negative.
The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.
The sBLA also includes overall survival (OS) data from the phase 3 TOWER trial, which is intended to support the conversion of blinatumomab’s accelerated approval to a full approval.
Results from the TOWER trial were recently published in NEJM.
In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.
Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).
The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).
The aim of this application is to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s current accelerated approval to a full approval.
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 Prescription Drug User Fee Act target action date for the blinatumomab sBLA is August 14, 2017.
About blinatumomab
Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
Blinatumomab currently has accelerated approval in the US as a treatment for adult and pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.
The FDA-approved prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities.
Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.
Blinatumomab is being developed and marketed by Amgen.
About the sBLA
With this sBLA, Amgen is seeking to make blinatumomab available as a treatment for patients with Philadelphia chromosome-positive (Ph+) relapsed/refractory BCP-ALL (as well as Ph-).
To this end, the application includes data from the ALCANTARA study, which were just published in the Journal of Clinical Oncology.
In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.
Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease negative.
The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.
The sBLA also includes overall survival (OS) data from the phase 3 TOWER trial, which is intended to support the conversion of blinatumomab’s accelerated approval to a full approval.
Results from the TOWER trial were recently published in NEJM.
In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.
Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).
The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.
The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).
The aim of this application is to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s current accelerated approval to a full approval.
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 Prescription Drug User Fee Act target action date for the blinatumomab sBLA is August 14, 2017.
About blinatumomab
Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
Blinatumomab currently has accelerated approval in the US as a treatment for adult and pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.
The FDA-approved prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities.
Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.
Blinatumomab is being developed and marketed by Amgen.
About the sBLA
With this sBLA, Amgen is seeking to make blinatumomab available as a treatment for patients with Philadelphia chromosome-positive (Ph+) relapsed/refractory BCP-ALL (as well as Ph-).
To this end, the application includes data from the ALCANTARA study, which were just published in the Journal of Clinical Oncology.
In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.
Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease negative.
The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.
The sBLA also includes overall survival (OS) data from the phase 3 TOWER trial, which is intended to support the conversion of blinatumomab’s accelerated approval to a full approval.
Results from the TOWER trial were recently published in NEJM.
In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.
Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).
The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.
Warfarin, aspirin linked to higher risk of ICH in AFib
An analysis of data from the ARISTOTLE trial suggests patients with atrial fibrillation (AFib) have a higher risk of intracranial hemorrhage (ICH) when they receive warfarin as opposed to apixaban.
The analysis also indicates that concomitant aspirin use increases the risk of ICH among AFib patients taking either warfarin or apixaban as stroke prophylaxis.
“We know that aspirin has only a modest effect in preventing stroke in atrial fibrillation patients, yet it was one of the top predictors of intracranial hemorrhage,” said study author Renato D. Lopes, MD, PhD, of Duke Clinical Research Institute in Durham, North Carolina.
“Our finding demonstrates that aspirin is not as safe as one might think.”
Dr Lopes and his colleagues reported this finding in Blood.
Previous results from the ARISTOTLE trial, published in 2011, suggested that apixaban was superior to warfarin in terms of preventing stroke and systemic embolism, reducing bleeding, and reducing mortality in AFib patients.
However, a report published in 2013 suggested the results of this trial may have been affected by patients at 1 or more clinical trial sites receiving the wrong medication or dose, adverse events going unreported, and records being changed.
Bristol-Myers Squibb and Pfizer (funders of ARISTOTLE) said these issues likely had a negligible effect on the trial results. And the US Food and Drug Administration agreed when it approved apixaban for use in AFib patients in 2013.
Current analysis
For the current analysis, researchers used ARISTOTLE data to investigate the frequency and characteristics of ICH. They analyzed data from 18,140 AFib patients treated with warfarin or apixaban at sites in North America, Latin America, Europe, and Asia.
In all, 174 patients developed ICH. Most of these bleeds were spontaneous (71.2%) rather than traumatic (28.8%).
Apixaban vs warfarin
Patients randomized to receive apixaban had a lower incidence of ICH than those randomized to warfarin—0.33% per year and 0.80% per year, respectively.
The risk of ICH was significantly lower in the apixaban arm than the warfarin arm (hazard ratio [HR]=0.42, 95% CI 0.30–0.58; P<0.0001). The same was true for spontaneous ICH (HR=0.52, 95% CI 190 0.35–0.75; P=0.0006) and traumatic ICH (HR=0.26, 95% CI 0.13–0.53; P=0.0002).
In the warfarin arm, the median time from the most recent international normalized ratio (INR) test to ICH was 13 days (range, 6-21).
Most patients (78.5%) in the warfarin arm who developed ICH had a pre-ICH INR below 3.0. The median INR was 2.6 (range, 2.1-3.0).
Other risk factors
The researchers found that several factors other than study treatment were associated with an increased risk of ICH.
Patients treated at trial sites in Asia (HR=3.19) or Latin America (HR=1.57) had an increased risk of ICH compared to patients treated in Europe.
Each 5-year increase in patient age was associated with an increased risk of ICH (HR=1.25.)
Patients with a prior stroke or transient ischemic attack (HR=1.83) had an increased risk of ICH, as did patients receiving aspirin at baseline (HR=1.37).
The researchers said the increased risk of ICH associated with aspirin use was particularly pronounced in older patients.
An analysis of data from the ARISTOTLE trial suggests patients with atrial fibrillation (AFib) have a higher risk of intracranial hemorrhage (ICH) when they receive warfarin as opposed to apixaban.
The analysis also indicates that concomitant aspirin use increases the risk of ICH among AFib patients taking either warfarin or apixaban as stroke prophylaxis.
“We know that aspirin has only a modest effect in preventing stroke in atrial fibrillation patients, yet it was one of the top predictors of intracranial hemorrhage,” said study author Renato D. Lopes, MD, PhD, of Duke Clinical Research Institute in Durham, North Carolina.
“Our finding demonstrates that aspirin is not as safe as one might think.”
Dr Lopes and his colleagues reported this finding in Blood.
Previous results from the ARISTOTLE trial, published in 2011, suggested that apixaban was superior to warfarin in terms of preventing stroke and systemic embolism, reducing bleeding, and reducing mortality in AFib patients.
However, a report published in 2013 suggested the results of this trial may have been affected by patients at 1 or more clinical trial sites receiving the wrong medication or dose, adverse events going unreported, and records being changed.
Bristol-Myers Squibb and Pfizer (funders of ARISTOTLE) said these issues likely had a negligible effect on the trial results. And the US Food and Drug Administration agreed when it approved apixaban for use in AFib patients in 2013.
Current analysis
For the current analysis, researchers used ARISTOTLE data to investigate the frequency and characteristics of ICH. They analyzed data from 18,140 AFib patients treated with warfarin or apixaban at sites in North America, Latin America, Europe, and Asia.
In all, 174 patients developed ICH. Most of these bleeds were spontaneous (71.2%) rather than traumatic (28.8%).
Apixaban vs warfarin
Patients randomized to receive apixaban had a lower incidence of ICH than those randomized to warfarin—0.33% per year and 0.80% per year, respectively.
The risk of ICH was significantly lower in the apixaban arm than the warfarin arm (hazard ratio [HR]=0.42, 95% CI 0.30–0.58; P<0.0001). The same was true for spontaneous ICH (HR=0.52, 95% CI 190 0.35–0.75; P=0.0006) and traumatic ICH (HR=0.26, 95% CI 0.13–0.53; P=0.0002).
In the warfarin arm, the median time from the most recent international normalized ratio (INR) test to ICH was 13 days (range, 6-21).
Most patients (78.5%) in the warfarin arm who developed ICH had a pre-ICH INR below 3.0. The median INR was 2.6 (range, 2.1-3.0).
Other risk factors
The researchers found that several factors other than study treatment were associated with an increased risk of ICH.
Patients treated at trial sites in Asia (HR=3.19) or Latin America (HR=1.57) had an increased risk of ICH compared to patients treated in Europe.
Each 5-year increase in patient age was associated with an increased risk of ICH (HR=1.25.)
Patients with a prior stroke or transient ischemic attack (HR=1.83) had an increased risk of ICH, as did patients receiving aspirin at baseline (HR=1.37).
The researchers said the increased risk of ICH associated with aspirin use was particularly pronounced in older patients.
An analysis of data from the ARISTOTLE trial suggests patients with atrial fibrillation (AFib) have a higher risk of intracranial hemorrhage (ICH) when they receive warfarin as opposed to apixaban.
The analysis also indicates that concomitant aspirin use increases the risk of ICH among AFib patients taking either warfarin or apixaban as stroke prophylaxis.
“We know that aspirin has only a modest effect in preventing stroke in atrial fibrillation patients, yet it was one of the top predictors of intracranial hemorrhage,” said study author Renato D. Lopes, MD, PhD, of Duke Clinical Research Institute in Durham, North Carolina.
“Our finding demonstrates that aspirin is not as safe as one might think.”
Dr Lopes and his colleagues reported this finding in Blood.
Previous results from the ARISTOTLE trial, published in 2011, suggested that apixaban was superior to warfarin in terms of preventing stroke and systemic embolism, reducing bleeding, and reducing mortality in AFib patients.
However, a report published in 2013 suggested the results of this trial may have been affected by patients at 1 or more clinical trial sites receiving the wrong medication or dose, adverse events going unreported, and records being changed.
Bristol-Myers Squibb and Pfizer (funders of ARISTOTLE) said these issues likely had a negligible effect on the trial results. And the US Food and Drug Administration agreed when it approved apixaban for use in AFib patients in 2013.
Current analysis
For the current analysis, researchers used ARISTOTLE data to investigate the frequency and characteristics of ICH. They analyzed data from 18,140 AFib patients treated with warfarin or apixaban at sites in North America, Latin America, Europe, and Asia.
In all, 174 patients developed ICH. Most of these bleeds were spontaneous (71.2%) rather than traumatic (28.8%).
Apixaban vs warfarin
Patients randomized to receive apixaban had a lower incidence of ICH than those randomized to warfarin—0.33% per year and 0.80% per year, respectively.
The risk of ICH was significantly lower in the apixaban arm than the warfarin arm (hazard ratio [HR]=0.42, 95% CI 0.30–0.58; P<0.0001). The same was true for spontaneous ICH (HR=0.52, 95% CI 190 0.35–0.75; P=0.0006) and traumatic ICH (HR=0.26, 95% CI 0.13–0.53; P=0.0002).
In the warfarin arm, the median time from the most recent international normalized ratio (INR) test to ICH was 13 days (range, 6-21).
Most patients (78.5%) in the warfarin arm who developed ICH had a pre-ICH INR below 3.0. The median INR was 2.6 (range, 2.1-3.0).
Other risk factors
The researchers found that several factors other than study treatment were associated with an increased risk of ICH.
Patients treated at trial sites in Asia (HR=3.19) or Latin America (HR=1.57) had an increased risk of ICH compared to patients treated in Europe.
Each 5-year increase in patient age was associated with an increased risk of ICH (HR=1.25.)
Patients with a prior stroke or transient ischemic attack (HR=1.83) had an increased risk of ICH, as did patients receiving aspirin at baseline (HR=1.37).
The researchers said the increased risk of ICH associated with aspirin use was particularly pronounced in older patients.
Studies support Zika screening in entire US blood supply
Results from a pair of studies suggest it is necessary to test for Zika virus in all blood donated in the US, even blood collected outside areas of active Zika transmission.
Last year, the US Food and Drug Administration recommended that all states and US territories screen donated whole blood and blood components for the Zika virus.
Two studies published in Transfusion support that recommendation by revealing the presence of blood donors who tested positive for Zika and may have acquired the infection via travel or sexual contact.
In the first study, researchers screened donor plasma samples using the cobas Zika test. Some of the researchers are employees/contractors of Roche Molecular Systems, Inc., which developed the test.
The study included 358,786 blood donations made in US states. Plasma samples from 23 of the donors were reactive on the first test.
For these cases, the testing lab performed repeat tests with cobas Zika. The lab also simulated minipool testing by diluting a donor sample 1:6 with Zika-negative human plasma. In addition, the reactive samples were sent out for alternate nucleic acid testing and serology testing.
The additional tests suggested 14 of the samples were positive for the Zika virus.
Ten of the 14 donors said they had traveled to an area of active Zika transmission within 90 days of their donation, and 3 of the 10 donors also had a sexual exposure risk. The median time from the end of the donors’ travel to their donation was 25 days (range, 6-71).
Three donors had not traveled to an area of active Zika transmission outside the US, but they lived in Miami-Dade County and were thought to have contracted the virus there.
For the remaining donor, there was no information on travel or sexual exposure risk.
The researchers said minipool testing likely would have identified half of the Zika-positive donations, as only 7 of the 14 donations with probable Zika virus infection were detectable via the simulated minipool testing.
The team also said the estimated specificity of the cobas Zika test was 99.997%.
In the second study, researchers screened donor plasma samples using the Procleix Zika virus assay. Some of the researchers are employees/contractors of Hologic, Inc., and Grifols Diagnostic Solutions, Inc., the companies that co-developed the assay.
The study included 466,834 blood donations in the US (outside of Puerto Rico and Florida). Twenty donor samples were reactive on the initial test.
These 20 samples (and additional samples from these donors) underwent subsequent testing with the Procleix Zika virus assay, real-time polymerase chain reaction, and Zika virus IgG and IgM capture ELISAs.
According to subsequent tests, 5 donors were reactive for Zika virus RNA. All of these donations were collected outside areas of active Zika transmission, but all 5 donors had traveled to areas of active transmission.
The researchers said the estimated specificity of the Procleix Zika virus assay was 99.997%.
The team also reported transfusion of an apheresis platelet donation from 1 of the 5 Zika-positive donors. The recipient of this product did not develop Zika infection, which suggests these units may not be infectious.
However, other researchers previously reported what they believed to be transmission of the Zika virus via platelet transfusion.
Results from a pair of studies suggest it is necessary to test for Zika virus in all blood donated in the US, even blood collected outside areas of active Zika transmission.
Last year, the US Food and Drug Administration recommended that all states and US territories screen donated whole blood and blood components for the Zika virus.
Two studies published in Transfusion support that recommendation by revealing the presence of blood donors who tested positive for Zika and may have acquired the infection via travel or sexual contact.
In the first study, researchers screened donor plasma samples using the cobas Zika test. Some of the researchers are employees/contractors of Roche Molecular Systems, Inc., which developed the test.
The study included 358,786 blood donations made in US states. Plasma samples from 23 of the donors were reactive on the first test.
For these cases, the testing lab performed repeat tests with cobas Zika. The lab also simulated minipool testing by diluting a donor sample 1:6 with Zika-negative human plasma. In addition, the reactive samples were sent out for alternate nucleic acid testing and serology testing.
The additional tests suggested 14 of the samples were positive for the Zika virus.
Ten of the 14 donors said they had traveled to an area of active Zika transmission within 90 days of their donation, and 3 of the 10 donors also had a sexual exposure risk. The median time from the end of the donors’ travel to their donation was 25 days (range, 6-71).
Three donors had not traveled to an area of active Zika transmission outside the US, but they lived in Miami-Dade County and were thought to have contracted the virus there.
For the remaining donor, there was no information on travel or sexual exposure risk.
The researchers said minipool testing likely would have identified half of the Zika-positive donations, as only 7 of the 14 donations with probable Zika virus infection were detectable via the simulated minipool testing.
The team also said the estimated specificity of the cobas Zika test was 99.997%.
In the second study, researchers screened donor plasma samples using the Procleix Zika virus assay. Some of the researchers are employees/contractors of Hologic, Inc., and Grifols Diagnostic Solutions, Inc., the companies that co-developed the assay.
The study included 466,834 blood donations in the US (outside of Puerto Rico and Florida). Twenty donor samples were reactive on the initial test.
These 20 samples (and additional samples from these donors) underwent subsequent testing with the Procleix Zika virus assay, real-time polymerase chain reaction, and Zika virus IgG and IgM capture ELISAs.
According to subsequent tests, 5 donors were reactive for Zika virus RNA. All of these donations were collected outside areas of active Zika transmission, but all 5 donors had traveled to areas of active transmission.
The researchers said the estimated specificity of the Procleix Zika virus assay was 99.997%.
The team also reported transfusion of an apheresis platelet donation from 1 of the 5 Zika-positive donors. The recipient of this product did not develop Zika infection, which suggests these units may not be infectious.
However, other researchers previously reported what they believed to be transmission of the Zika virus via platelet transfusion.
Results from a pair of studies suggest it is necessary to test for Zika virus in all blood donated in the US, even blood collected outside areas of active Zika transmission.
Last year, the US Food and Drug Administration recommended that all states and US territories screen donated whole blood and blood components for the Zika virus.
Two studies published in Transfusion support that recommendation by revealing the presence of blood donors who tested positive for Zika and may have acquired the infection via travel or sexual contact.
In the first study, researchers screened donor plasma samples using the cobas Zika test. Some of the researchers are employees/contractors of Roche Molecular Systems, Inc., which developed the test.
The study included 358,786 blood donations made in US states. Plasma samples from 23 of the donors were reactive on the first test.
For these cases, the testing lab performed repeat tests with cobas Zika. The lab also simulated minipool testing by diluting a donor sample 1:6 with Zika-negative human plasma. In addition, the reactive samples were sent out for alternate nucleic acid testing and serology testing.
The additional tests suggested 14 of the samples were positive for the Zika virus.
Ten of the 14 donors said they had traveled to an area of active Zika transmission within 90 days of their donation, and 3 of the 10 donors also had a sexual exposure risk. The median time from the end of the donors’ travel to their donation was 25 days (range, 6-71).
Three donors had not traveled to an area of active Zika transmission outside the US, but they lived in Miami-Dade County and were thought to have contracted the virus there.
For the remaining donor, there was no information on travel or sexual exposure risk.
The researchers said minipool testing likely would have identified half of the Zika-positive donations, as only 7 of the 14 donations with probable Zika virus infection were detectable via the simulated minipool testing.
The team also said the estimated specificity of the cobas Zika test was 99.997%.
In the second study, researchers screened donor plasma samples using the Procleix Zika virus assay. Some of the researchers are employees/contractors of Hologic, Inc., and Grifols Diagnostic Solutions, Inc., the companies that co-developed the assay.
The study included 466,834 blood donations in the US (outside of Puerto Rico and Florida). Twenty donor samples were reactive on the initial test.
These 20 samples (and additional samples from these donors) underwent subsequent testing with the Procleix Zika virus assay, real-time polymerase chain reaction, and Zika virus IgG and IgM capture ELISAs.
According to subsequent tests, 5 donors were reactive for Zika virus RNA. All of these donations were collected outside areas of active Zika transmission, but all 5 donors had traveled to areas of active transmission.
The researchers said the estimated specificity of the Procleix Zika virus assay was 99.997%.
The team also reported transfusion of an apheresis platelet donation from 1 of the 5 Zika-positive donors. The recipient of this product did not develop Zika infection, which suggests these units may not be infectious.
However, other researchers previously reported what they believed to be transmission of the Zika virus via platelet transfusion.
FDA grants priority review for BLA of CAR T-cell therapy
The US Food and Drug Administration (FDA) has granted priority review for a biologics license application (BLA) for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
The BLA is for CTL019 as a treatment for pediatric patients and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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 accepted the BLA for CTL019 yesterday, according to Novartis.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
CTL019 already has breakthrough therapy designation for the treatment of adults and children with relapsed/refractory ALL.
Novartis said it is planning additional filings for CTL019 in the US and European Union later this year, including a BLA with the FDA for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and applications for marketing authorization with the European Medicines Agency in relapsed/refractory B-cell ALL and relapsed/refractory DLBCL.
Trials of CTL019 in ALL
The priority review designation for CTL019 is based on results from the Novartis-sponsored ELIANA study (NCT02435849). Results from this international, phase 2 trial were presented at ASH 2016.
The trial enrolled patients who had CD19-positive B-ALL with morphologic marrow tumor involvement at registration (>5% blasts) and were primary refractory, were chemo-refractory after first relapse, had relapsed after second-line therapy, or were ineligible for allogeneic hematopoietic stem cell transplant.
Most patients received fludarabine/cyclophosphamide lymphodepleting chemotherapy followed by a single dose of CTL019.
Three months post-infusion, 82% of patients (41/50) had achieved a complete response or complete response with incomplete blood count recovery.
Nearly half of the patients in the trial (48%) experienced grade 3/4 cytokine release syndrome (CRS), though there were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events, including confusion, delirium, encephalopathy, agitation, and seizure.
The BLA for CTL019 is also supported by results from the phase 2 ENSIGN trial, which were presented at ASH 2016, and results of a pilot study in patients with relapsed/refractory ALL, which were presented at ASH 2015.
The US Food and Drug Administration (FDA) has granted priority review for a biologics license application (BLA) for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
The BLA is for CTL019 as a treatment for pediatric patients and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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 accepted the BLA for CTL019 yesterday, according to Novartis.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
CTL019 already has breakthrough therapy designation for the treatment of adults and children with relapsed/refractory ALL.
Novartis said it is planning additional filings for CTL019 in the US and European Union later this year, including a BLA with the FDA for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and applications for marketing authorization with the European Medicines Agency in relapsed/refractory B-cell ALL and relapsed/refractory DLBCL.
Trials of CTL019 in ALL
The priority review designation for CTL019 is based on results from the Novartis-sponsored ELIANA study (NCT02435849). Results from this international, phase 2 trial were presented at ASH 2016.
The trial enrolled patients who had CD19-positive B-ALL with morphologic marrow tumor involvement at registration (>5% blasts) and were primary refractory, were chemo-refractory after first relapse, had relapsed after second-line therapy, or were ineligible for allogeneic hematopoietic stem cell transplant.
Most patients received fludarabine/cyclophosphamide lymphodepleting chemotherapy followed by a single dose of CTL019.
Three months post-infusion, 82% of patients (41/50) had achieved a complete response or complete response with incomplete blood count recovery.
Nearly half of the patients in the trial (48%) experienced grade 3/4 cytokine release syndrome (CRS), though there were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events, including confusion, delirium, encephalopathy, agitation, and seizure.
The BLA for CTL019 is also supported by results from the phase 2 ENSIGN trial, which were presented at ASH 2016, and results of a pilot study in patients with relapsed/refractory ALL, which were presented at ASH 2015.
The US Food and Drug Administration (FDA) has granted priority review for a biologics license application (BLA) for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
The BLA is for CTL019 as a treatment for pediatric patients and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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 accepted the BLA for CTL019 yesterday, according to Novartis.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
CTL019 already has breakthrough therapy designation for the treatment of adults and children with relapsed/refractory ALL.
Novartis said it is planning additional filings for CTL019 in the US and European Union later this year, including a BLA with the FDA for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and applications for marketing authorization with the European Medicines Agency in relapsed/refractory B-cell ALL and relapsed/refractory DLBCL.
Trials of CTL019 in ALL
The priority review designation for CTL019 is based on results from the Novartis-sponsored ELIANA study (NCT02435849). Results from this international, phase 2 trial were presented at ASH 2016.
The trial enrolled patients who had CD19-positive B-ALL with morphologic marrow tumor involvement at registration (>5% blasts) and were primary refractory, were chemo-refractory after first relapse, had relapsed after second-line therapy, or were ineligible for allogeneic hematopoietic stem cell transplant.
Most patients received fludarabine/cyclophosphamide lymphodepleting chemotherapy followed by a single dose of CTL019.
Three months post-infusion, 82% of patients (41/50) had achieved a complete response or complete response with incomplete blood count recovery.
Nearly half of the patients in the trial (48%) experienced grade 3/4 cytokine release syndrome (CRS), though there were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events, including confusion, delirium, encephalopathy, agitation, and seizure.
The BLA for CTL019 is also supported by results from the phase 2 ENSIGN trial, which were presented at ASH 2016, and results of a pilot study in patients with relapsed/refractory ALL, which were presented at ASH 2015.
Team identifies proteins that give malaria parasites ‘superpower’
Researchers say they have identified proteins that enable the malaria parasite Plasmodium falciparum to “walk through cell walls.”
The team believes the proteins—SPECT and PLP1—could be targeted to develop antimalarial drugs or vaccines.
Justin Boddey, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues described this research in Cell Reports.
“The malaria infection cycle begins with a mosquito bite, when parasites are injected into the skin, and then rapidly move to the liver,” Dr Boddey explained. “We have shown that P falciparum employs a technique called cell traversal to quickly move through host cells in their path as they seek out liver cells to infect.”
“Our study identified that P falciparum parasites traverse human cells—effectively walking through cell walls—using 2 proteins called SPECT and PLP1 to achieve this superpower. This allows parasites to get from the skin to the liver very quickly following a mosquito bite.”
Dr Boddey said pinpointing these proteins was a good avenue for new therapies.
“Our long-term goal is to eradicate malaria, so we have to look at ways of breaking the cycle of infection,” he said. “A vaccine or treatment that halts the liver-stage infection offers the best chance of eradication because it stops parasites before they take hold.”
Researchers say they have identified proteins that enable the malaria parasite Plasmodium falciparum to “walk through cell walls.”
The team believes the proteins—SPECT and PLP1—could be targeted to develop antimalarial drugs or vaccines.
Justin Boddey, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues described this research in Cell Reports.
“The malaria infection cycle begins with a mosquito bite, when parasites are injected into the skin, and then rapidly move to the liver,” Dr Boddey explained. “We have shown that P falciparum employs a technique called cell traversal to quickly move through host cells in their path as they seek out liver cells to infect.”
“Our study identified that P falciparum parasites traverse human cells—effectively walking through cell walls—using 2 proteins called SPECT and PLP1 to achieve this superpower. This allows parasites to get from the skin to the liver very quickly following a mosquito bite.”
Dr Boddey said pinpointing these proteins was a good avenue for new therapies.
“Our long-term goal is to eradicate malaria, so we have to look at ways of breaking the cycle of infection,” he said. “A vaccine or treatment that halts the liver-stage infection offers the best chance of eradication because it stops parasites before they take hold.”
Researchers say they have identified proteins that enable the malaria parasite Plasmodium falciparum to “walk through cell walls.”
The team believes the proteins—SPECT and PLP1—could be targeted to develop antimalarial drugs or vaccines.
Justin Boddey, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues described this research in Cell Reports.
“The malaria infection cycle begins with a mosquito bite, when parasites are injected into the skin, and then rapidly move to the liver,” Dr Boddey explained. “We have shown that P falciparum employs a technique called cell traversal to quickly move through host cells in their path as they seek out liver cells to infect.”
“Our study identified that P falciparum parasites traverse human cells—effectively walking through cell walls—using 2 proteins called SPECT and PLP1 to achieve this superpower. This allows parasites to get from the skin to the liver very quickly following a mosquito bite.”
Dr Boddey said pinpointing these proteins was a good avenue for new therapies.
“Our long-term goal is to eradicate malaria, so we have to look at ways of breaking the cycle of infection,” he said. “A vaccine or treatment that halts the liver-stage infection offers the best chance of eradication because it stops parasites before they take hold.”