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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.
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.
Drug receives orphan designation for AML
The US Food and Drug Administration (FDA) has granted annamycin orphan designation for the treatment of acute myeloid leukemia (AML).
Annamycin is a liposomal anthracycline under development by Moleculin Biotech, Inc.
The company said it is working with the FDA on an investigative new drug application for a phase 1/2 trial of annamycin in patients with relapsed or refractory AML.
Annamycin has already been tested in 6 clinical trials, 3 of which focused on leukemia.
Results from one of these trials, in adults with relapsed/refractory acute lymphoblastic leukemia, were published in Clinical Lymphoma, Myeloma & Leukemia in 2013.
Annamycin has been under development by several other pharmaceutical companies. Moleculin Biotech, Inc. acquired rights and development assets relating to the drug in 2015.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted annamycin orphan designation for the treatment of acute myeloid leukemia (AML).
Annamycin is a liposomal anthracycline under development by Moleculin Biotech, Inc.
The company said it is working with the FDA on an investigative new drug application for a phase 1/2 trial of annamycin in patients with relapsed or refractory AML.
Annamycin has already been tested in 6 clinical trials, 3 of which focused on leukemia.
Results from one of these trials, in adults with relapsed/refractory acute lymphoblastic leukemia, were published in Clinical Lymphoma, Myeloma & Leukemia in 2013.
Annamycin has been under development by several other pharmaceutical companies. Moleculin Biotech, Inc. acquired rights and development assets relating to the drug in 2015.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted annamycin orphan designation for the treatment of acute myeloid leukemia (AML).
Annamycin is a liposomal anthracycline under development by Moleculin Biotech, Inc.
The company said it is working with the FDA on an investigative new drug application for a phase 1/2 trial of annamycin in patients with relapsed or refractory AML.
Annamycin has already been tested in 6 clinical trials, 3 of which focused on leukemia.
Results from one of these trials, in adults with relapsed/refractory acute lymphoblastic leukemia, were published in Clinical Lymphoma, Myeloma & Leukemia in 2013.
Annamycin has been under development by several other pharmaceutical companies. Moleculin Biotech, Inc. acquired rights and development assets relating to the drug in 2015.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.
Company again withdraws application for pacritinib
CTI BioPharma has withdrawn its application for marketing authorization of pacritinib (Enpaxiq) in the European Union, according to the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The company was seeking approval for pacritinib, a JAK2/FLT3 inhibitor, to treat splenomegaly or symptoms of myelofibrosis (MF) in adults with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
When the application was withdrawn, the CHMP was of the provisional opinion that pacritinib could not have been approved for this indication.
Last year, CTI BioPharma withdrew its application for approval of pacritinib in the US.
Issues preventing approval
The CHMP said it had a number of concerns related to the PERSIST-1 trial, which was used to support the application for approval in the European Union. In this trial, researchers compared pacritinib to best available therapy, excluding JAK inhibitors, in patients with MF.
The CHMP said the reduction in spleen size, which was the main efficacy outcome in the study, appeared to be lower with pacritinib than with another medicine of its class, with no improvement in symptom scores.
In addition, the incidence of thrombocytopenia was higher in patients treated with pacritinib.
And more deaths occurred in patients taking pacritinib than in those receiving best available therapy, including deaths due to bleeding and adverse effects on the heart.
The CHMP also said it needs more information about the starting materials used in the manufacture of pacritinib and how the drug acts on target proteins.
Given these concerns, the CHMP was of the opinion that pacritinib’s benefits had not been shown to outweigh its risks.
CTI BioPharma said it could address the CHMP’s concerns by providing data from a second study of pacritinib, PERSIST-2.
However, there was not enough time in the current application procedure to provide the data, so the company decided to withdraw the application.
CTI BioPharma said it intends to integrate data from PERSIST-2 into its current dossier before approaching the European Medicines Agency to discuss a new application.
The company also said the withdrawal of its application will not affect patients currently enrolled in clinical trials of pacritinib or compassionate use programs for the drug.
Previous withdrawal, clinical hold
CTI BioPharma withdrew its application for approval of pacritinib in the US after the US Food and Drug Administration (FDA) placed a full clinical hold on trials of the drug.
The FDA placed the hold on pacritinib trials in February 2016 after results from PERSIST-1 and PERSIST-2 showed excess mortality in patients who received pacritinib.
The FDA lifted the hold in January 2017 after CTI BioPharma agreed to conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, and make modifications to protocols and study-related documents.
CTI BioPharma has withdrawn its application for marketing authorization of pacritinib (Enpaxiq) in the European Union, according to the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The company was seeking approval for pacritinib, a JAK2/FLT3 inhibitor, to treat splenomegaly or symptoms of myelofibrosis (MF) in adults with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
When the application was withdrawn, the CHMP was of the provisional opinion that pacritinib could not have been approved for this indication.
Last year, CTI BioPharma withdrew its application for approval of pacritinib in the US.
Issues preventing approval
The CHMP said it had a number of concerns related to the PERSIST-1 trial, which was used to support the application for approval in the European Union. In this trial, researchers compared pacritinib to best available therapy, excluding JAK inhibitors, in patients with MF.
The CHMP said the reduction in spleen size, which was the main efficacy outcome in the study, appeared to be lower with pacritinib than with another medicine of its class, with no improvement in symptom scores.
In addition, the incidence of thrombocytopenia was higher in patients treated with pacritinib.
And more deaths occurred in patients taking pacritinib than in those receiving best available therapy, including deaths due to bleeding and adverse effects on the heart.
The CHMP also said it needs more information about the starting materials used in the manufacture of pacritinib and how the drug acts on target proteins.
Given these concerns, the CHMP was of the opinion that pacritinib’s benefits had not been shown to outweigh its risks.
CTI BioPharma said it could address the CHMP’s concerns by providing data from a second study of pacritinib, PERSIST-2.
However, there was not enough time in the current application procedure to provide the data, so the company decided to withdraw the application.
CTI BioPharma said it intends to integrate data from PERSIST-2 into its current dossier before approaching the European Medicines Agency to discuss a new application.
The company also said the withdrawal of its application will not affect patients currently enrolled in clinical trials of pacritinib or compassionate use programs for the drug.
Previous withdrawal, clinical hold
CTI BioPharma withdrew its application for approval of pacritinib in the US after the US Food and Drug Administration (FDA) placed a full clinical hold on trials of the drug.
The FDA placed the hold on pacritinib trials in February 2016 after results from PERSIST-1 and PERSIST-2 showed excess mortality in patients who received pacritinib.
The FDA lifted the hold in January 2017 after CTI BioPharma agreed to conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, and make modifications to protocols and study-related documents.
CTI BioPharma has withdrawn its application for marketing authorization of pacritinib (Enpaxiq) in the European Union, according to the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The company was seeking approval for pacritinib, a JAK2/FLT3 inhibitor, to treat splenomegaly or symptoms of myelofibrosis (MF) in adults with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
When the application was withdrawn, the CHMP was of the provisional opinion that pacritinib could not have been approved for this indication.
Last year, CTI BioPharma withdrew its application for approval of pacritinib in the US.
Issues preventing approval
The CHMP said it had a number of concerns related to the PERSIST-1 trial, which was used to support the application for approval in the European Union. In this trial, researchers compared pacritinib to best available therapy, excluding JAK inhibitors, in patients with MF.
The CHMP said the reduction in spleen size, which was the main efficacy outcome in the study, appeared to be lower with pacritinib than with another medicine of its class, with no improvement in symptom scores.
In addition, the incidence of thrombocytopenia was higher in patients treated with pacritinib.
And more deaths occurred in patients taking pacritinib than in those receiving best available therapy, including deaths due to bleeding and adverse effects on the heart.
The CHMP also said it needs more information about the starting materials used in the manufacture of pacritinib and how the drug acts on target proteins.
Given these concerns, the CHMP was of the opinion that pacritinib’s benefits had not been shown to outweigh its risks.
CTI BioPharma said it could address the CHMP’s concerns by providing data from a second study of pacritinib, PERSIST-2.
However, there was not enough time in the current application procedure to provide the data, so the company decided to withdraw the application.
CTI BioPharma said it intends to integrate data from PERSIST-2 into its current dossier before approaching the European Medicines Agency to discuss a new application.
The company also said the withdrawal of its application will not affect patients currently enrolled in clinical trials of pacritinib or compassionate use programs for the drug.
Previous withdrawal, clinical hold
CTI BioPharma withdrew its application for approval of pacritinib in the US after the US Food and Drug Administration (FDA) placed a full clinical hold on trials of the drug.
The FDA placed the hold on pacritinib trials in February 2016 after results from PERSIST-1 and PERSIST-2 showed excess mortality in patients who received pacritinib.
The FDA lifted the hold in January 2017 after CTI BioPharma agreed to conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, and make modifications to protocols and study-related documents.
CHMP recommends product for hemophilia B
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).
N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.
The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.
The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.
Trial results
The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.
Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.
In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.
Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.
Safety
None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.
Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.
There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.
These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.
Efficacy
The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.
The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.
There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.
The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).
N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.
The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.
The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.
Trial results
The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.
Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.
In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.
Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.
Safety
None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.
Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.
There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.
These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.
Efficacy
The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.
The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.
There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.
The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).
N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.
The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.
The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.
Trial results
The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.
Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.
In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.
Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.
Safety
None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.
Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.
There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.
These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.
Efficacy
The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.
The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.
There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.
The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.
CHMP recommends drug for relapsed/refractory cHL
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.
The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.
Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.
The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).
KEYNOTE-087
KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
- Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
- Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
- Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.
KEYNOTE-013
KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.
Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.
The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.
The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.
The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.
The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.
The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).
The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).
AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.
The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.
Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.
The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).
KEYNOTE-087
KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
- Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
- Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
- Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.
KEYNOTE-013
KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.
Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.
The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.
The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.
The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.
The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.
The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).
The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).
AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.
The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.
Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.
The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).
KEYNOTE-087
KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
- Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
- Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
- Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.
KEYNOTE-013
KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.
Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.
The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.
The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.
The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.
The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.
The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).
The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).
AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.
New resource designed to help prevent CINV
The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.
The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.
The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.
The entire toolkit is available for free download at TimeToTalkCINV.com.
The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).
The campaign began in response to results from a survey of cancer patients.
“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.
“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”
The Time to Talk CINV toolkit includes the following resources:
- A list of myths and truths about CINV intended to eliminate common misperceptions
- A checklist of questions patients can ask healthcare providers to better understand CINV
- A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
- A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.
Each tool can be printed or filled out digitally.
Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.
The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.
The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.
The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.
The entire toolkit is available for free download at TimeToTalkCINV.com.
The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).
The campaign began in response to results from a survey of cancer patients.
“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.
“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”
The Time to Talk CINV toolkit includes the following resources:
- A list of myths and truths about CINV intended to eliminate common misperceptions
- A checklist of questions patients can ask healthcare providers to better understand CINV
- A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
- A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.
Each tool can be printed or filled out digitally.
Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.
The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.
The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.
The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.
The entire toolkit is available for free download at TimeToTalkCINV.com.
The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).
The campaign began in response to results from a survey of cancer patients.
“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.
“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”
The Time to Talk CINV toolkit includes the following resources:
- A list of myths and truths about CINV intended to eliminate common misperceptions
- A checklist of questions patients can ask healthcare providers to better understand CINV
- A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
- A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.
Each tool can be printed or filled out digitally.
Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.
FDA approves pembrolizumab to treat cHL
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
Selinexor trials placed on partial hold
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce 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 several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce 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 several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce 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 several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
Drug granted priority review for relapsed/refractory AML
The US Food and Drug Administration (FDA) has granted priority review for the new drug application (NDA) for enasidenib (AG-221), an inhibitor of mutant IDH2.
The drug is under review for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation.
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-month period.
The NDA for enasidenib has been given a Prescription Drug User Fee Act action date of August 30, 2017.
Enasidenib is being developed by Celgene Corporation and Agios Pharmaceuticals.
Phase 1/2 trial
The NDA submission for enasidenib is based on results from AG221-C-001, a single-arm, phase 1/2 study of the drug in patients with advanced hematologic malignancies with an IDH2 mutation.
Early data from the relapsed or refractory AML patients in this study were presented at the 2015 ASH Annual Meeting. (The presentation included updated data that differ from the data in the abstract.)
The trial included a dose-escalation phase and 5 expansion cohorts. The first 4 expansion cohorts had completed enrollment as of the presentation.
- Arm 1: 25 patients with IDH2-mutant-positive relapsed or refractory AML age ≥60 years, or any patient with AML regardless of age who relapsed after a bone marrow transplant (BMT)
- Arm 2: 25 patients with IDH2-mutant-positive relapsed or refractory AML age <60 years, excluding patients with AML who relapsed after a BMT
- Arm 3: 25 patients with IDH2-mutant-positive untreated AML age ≥60 years who decline standard of care chemotherapy
- Arm 4: 25 patients with IDH2-mutant-positive advanced hematologic malignancies not eligible for arms 1 to 3
- Arm 5: The phase 2 portion of the trial included 125 patients with IDH2-mutant-positive AML who were in second or later relapse, refractory to second-line induction or reinduction treatment, or relapsed after allogeneic transplant.
The data reported at ASH were from patients receiving enasidenib administered from 50-mg to 650-mg total daily doses in the dose-escalation arm and 100 mg once daily in the first 4 expansion arms, as of September 1, 2015.
The median age of these patients was 69 (range, 19-100). Patients with relapsed or refractory AML received a median of 2 prior lines of therapy (range, 1-6).
Safety data
A safety analysis was conducted for all 231 treated patients. As of the ASH presentation, a maximum tolerated dose of enasidenib had not been reached.
The majority of adverse events were mild to moderate, with the most common being nausea, diarrhea, fatigue, and febrile neutropenia.
Twenty-three percent of patients had treatment-related serious adverse events—notably, differentiation syndrome (4%), leukocytosis (4%), and nausea (2%).
Drug-related grade 5 serious adverse events include atrial flutter (n=1), cardiac tamponade (n=1), pericardial effusion (n=1), and respiratory failure (n=1).
Efficacy Data
Seventy-nine of the 209 response-evaluable patients achieved investigator-assessed objective responses, for an overall response rate of 38%.
There were 37 (18%) complete remissions (CR), 3 CRs with incomplete platelet recovery (CRp), 14 marrow CRs (mCR), 3 CRs with incomplete hematologic recovery (CRi), and 22 partial remissions (PR).
Of the 159 patients with relapsed or refractory AML, 59 (37%) achieved an objective response, including 29 (18%) CRs, 1 CRp, 9 mCRs, 3 CRis, and 17 PRs.
Of the 24 patients with AML who declined standard of care chemotherapy, 10 achieved an objective response, including 4 CRs, 1 CRp, 1 mCR, and 4 PRs.
The median duration of response was 6.9 months in patients with relapsed or refractory AML.
Responding relapsed/refractory AML patients were on study treatment for up to 18 months. The median duration of treatment was 6.8 months (range, 1.8 to 18 months). 
The US Food and Drug Administration (FDA) has granted priority review for the new drug application (NDA) for enasidenib (AG-221), an inhibitor of mutant IDH2.
The drug is under review for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation.
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-month period.
The NDA for enasidenib has been given a Prescription Drug User Fee Act action date of August 30, 2017.
Enasidenib is being developed by Celgene Corporation and Agios Pharmaceuticals.
Phase 1/2 trial
The NDA submission for enasidenib is based on results from AG221-C-001, a single-arm, phase 1/2 study of the drug in patients with advanced hematologic malignancies with an IDH2 mutation.
Early data from the relapsed or refractory AML patients in this study were presented at the 2015 ASH Annual Meeting. (The presentation included updated data that differ from the data in the abstract.)
The trial included a dose-escalation phase and 5 expansion cohorts. The first 4 expansion cohorts had completed enrollment as of the presentation.
- Arm 1: 25 patients with IDH2-mutant-positive relapsed or refractory AML age ≥60 years, or any patient with AML regardless of age who relapsed after a bone marrow transplant (BMT)
- Arm 2: 25 patients with IDH2-mutant-positive relapsed or refractory AML age <60 years, excluding patients with AML who relapsed after a BMT
- Arm 3: 25 patients with IDH2-mutant-positive untreated AML age ≥60 years who decline standard of care chemotherapy
- Arm 4: 25 patients with IDH2-mutant-positive advanced hematologic malignancies not eligible for arms 1 to 3
- Arm 5: The phase 2 portion of the trial included 125 patients with IDH2-mutant-positive AML who were in second or later relapse, refractory to second-line induction or reinduction treatment, or relapsed after allogeneic transplant.
The data reported at ASH were from patients receiving enasidenib administered from 50-mg to 650-mg total daily doses in the dose-escalation arm and 100 mg once daily in the first 4 expansion arms, as of September 1, 2015.
The median age of these patients was 69 (range, 19-100). Patients with relapsed or refractory AML received a median of 2 prior lines of therapy (range, 1-6).
Safety data
A safety analysis was conducted for all 231 treated patients. As of the ASH presentation, a maximum tolerated dose of enasidenib had not been reached.
The majority of adverse events were mild to moderate, with the most common being nausea, diarrhea, fatigue, and febrile neutropenia.
Twenty-three percent of patients had treatment-related serious adverse events—notably, differentiation syndrome (4%), leukocytosis (4%), and nausea (2%).
Drug-related grade 5 serious adverse events include atrial flutter (n=1), cardiac tamponade (n=1), pericardial effusion (n=1), and respiratory failure (n=1).
Efficacy Data
Seventy-nine of the 209 response-evaluable patients achieved investigator-assessed objective responses, for an overall response rate of 38%.
There were 37 (18%) complete remissions (CR), 3 CRs with incomplete platelet recovery (CRp), 14 marrow CRs (mCR), 3 CRs with incomplete hematologic recovery (CRi), and 22 partial remissions (PR).
Of the 159 patients with relapsed or refractory AML, 59 (37%) achieved an objective response, including 29 (18%) CRs, 1 CRp, 9 mCRs, 3 CRis, and 17 PRs.
Of the 24 patients with AML who declined standard of care chemotherapy, 10 achieved an objective response, including 4 CRs, 1 CRp, 1 mCR, and 4 PRs.
The median duration of response was 6.9 months in patients with relapsed or refractory AML.
Responding relapsed/refractory AML patients were on study treatment for up to 18 months. The median duration of treatment was 6.8 months (range, 1.8 to 18 months).
The US Food and Drug Administration (FDA) has granted priority review for the new drug application (NDA) for enasidenib (AG-221), an inhibitor of mutant IDH2.
The drug is under review for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation.
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-month period.
The NDA for enasidenib has been given a Prescription Drug User Fee Act action date of August 30, 2017.
Enasidenib is being developed by Celgene Corporation and Agios Pharmaceuticals.
Phase 1/2 trial
The NDA submission for enasidenib is based on results from AG221-C-001, a single-arm, phase 1/2 study of the drug in patients with advanced hematologic malignancies with an IDH2 mutation.
Early data from the relapsed or refractory AML patients in this study were presented at the 2015 ASH Annual Meeting. (The presentation included updated data that differ from the data in the abstract.)
The trial included a dose-escalation phase and 5 expansion cohorts. The first 4 expansion cohorts had completed enrollment as of the presentation.
- Arm 1: 25 patients with IDH2-mutant-positive relapsed or refractory AML age ≥60 years, or any patient with AML regardless of age who relapsed after a bone marrow transplant (BMT)
- Arm 2: 25 patients with IDH2-mutant-positive relapsed or refractory AML age <60 years, excluding patients with AML who relapsed after a BMT
- Arm 3: 25 patients with IDH2-mutant-positive untreated AML age ≥60 years who decline standard of care chemotherapy
- Arm 4: 25 patients with IDH2-mutant-positive advanced hematologic malignancies not eligible for arms 1 to 3
- Arm 5: The phase 2 portion of the trial included 125 patients with IDH2-mutant-positive AML who were in second or later relapse, refractory to second-line induction or reinduction treatment, or relapsed after allogeneic transplant.
The data reported at ASH were from patients receiving enasidenib administered from 50-mg to 650-mg total daily doses in the dose-escalation arm and 100 mg once daily in the first 4 expansion arms, as of September 1, 2015.
The median age of these patients was 69 (range, 19-100). Patients with relapsed or refractory AML received a median of 2 prior lines of therapy (range, 1-6).
Safety data
A safety analysis was conducted for all 231 treated patients. As of the ASH presentation, a maximum tolerated dose of enasidenib had not been reached.
The majority of adverse events were mild to moderate, with the most common being nausea, diarrhea, fatigue, and febrile neutropenia.
Twenty-three percent of patients had treatment-related serious adverse events—notably, differentiation syndrome (4%), leukocytosis (4%), and nausea (2%).
Drug-related grade 5 serious adverse events include atrial flutter (n=1), cardiac tamponade (n=1), pericardial effusion (n=1), and respiratory failure (n=1).
Efficacy Data
Seventy-nine of the 209 response-evaluable patients achieved investigator-assessed objective responses, for an overall response rate of 38%.
There were 37 (18%) complete remissions (CR), 3 CRs with incomplete platelet recovery (CRp), 14 marrow CRs (mCR), 3 CRs with incomplete hematologic recovery (CRi), and 22 partial remissions (PR).
Of the 159 patients with relapsed or refractory AML, 59 (37%) achieved an objective response, including 29 (18%) CRs, 1 CRp, 9 mCRs, 3 CRis, and 17 PRs.
Of the 24 patients with AML who declined standard of care chemotherapy, 10 achieved an objective response, including 4 CRs, 1 CRp, 1 mCR, and 4 PRs.
The median duration of response was 6.9 months in patients with relapsed or refractory AML.
Responding relapsed/refractory AML patients were on study treatment for up to 18 months. The median duration of treatment was 6.8 months (range, 1.8 to 18 months).