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Adjunct to HSCT receives orphan designation
The European Commission (EC) has granted orphan designation to NLA101 as an adjunct to hematopoietic stem cell transplant (HSCT).
NLA101 is a universal, off-the-shelf, stem and progenitor cell therapy intended to provide a short-term bridge for hematopoietic recovery while also providing long-term immunologic and clinical benefits in HSCT recipients.
NLA101 is a product of Nohla Therapeutics Inc.
The company says more than 125 infusions of NLA101 have been administered since 2009. The therapy is under investigation in patients receiving intensive chemotherapy as well as in HSCT recipients.
Results from a pilot study of NLA101 in HSCT recipients were presented at the 2014 ASH Annual Meeting.
In this study, 15 patients with hematologic malignancies underwent myeloablative cord blood transplant, with or without NLA101.
Patients who received NLA101 had a significantly reduced median time to platelet and neutrophil recovery, compared to controls. At 5 years, disease-free survival was 86% in the NLA101 group and 67% in the control group.
The rate of grade 3-4 acute graft-versus-host disease was 0% in the NLA101 group and 29% in the control group. The rate of transplant-related mortality was 0% and 22%, respectively.
Phase 2 studies of NLA101 in chemotherapy and HSCT recipients are ongoing.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure. 
The European Commission (EC) has granted orphan designation to NLA101 as an adjunct to hematopoietic stem cell transplant (HSCT).
NLA101 is a universal, off-the-shelf, stem and progenitor cell therapy intended to provide a short-term bridge for hematopoietic recovery while also providing long-term immunologic and clinical benefits in HSCT recipients.
NLA101 is a product of Nohla Therapeutics Inc.
The company says more than 125 infusions of NLA101 have been administered since 2009. The therapy is under investigation in patients receiving intensive chemotherapy as well as in HSCT recipients.
Results from a pilot study of NLA101 in HSCT recipients were presented at the 2014 ASH Annual Meeting.
In this study, 15 patients with hematologic malignancies underwent myeloablative cord blood transplant, with or without NLA101.
Patients who received NLA101 had a significantly reduced median time to platelet and neutrophil recovery, compared to controls. At 5 years, disease-free survival was 86% in the NLA101 group and 67% in the control group.
The rate of grade 3-4 acute graft-versus-host disease was 0% in the NLA101 group and 29% in the control group. The rate of transplant-related mortality was 0% and 22%, respectively.
Phase 2 studies of NLA101 in chemotherapy and HSCT recipients are ongoing.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission (EC) has granted orphan designation to NLA101 as an adjunct to hematopoietic stem cell transplant (HSCT).
NLA101 is a universal, off-the-shelf, stem and progenitor cell therapy intended to provide a short-term bridge for hematopoietic recovery while also providing long-term immunologic and clinical benefits in HSCT recipients.
NLA101 is a product of Nohla Therapeutics Inc.
The company says more than 125 infusions of NLA101 have been administered since 2009. The therapy is under investigation in patients receiving intensive chemotherapy as well as in HSCT recipients.
Results from a pilot study of NLA101 in HSCT recipients were presented at the 2014 ASH Annual Meeting.
In this study, 15 patients with hematologic malignancies underwent myeloablative cord blood transplant, with or without NLA101.
Patients who received NLA101 had a significantly reduced median time to platelet and neutrophil recovery, compared to controls. At 5 years, disease-free survival was 86% in the NLA101 group and 67% in the control group.
The rate of grade 3-4 acute graft-versus-host disease was 0% in the NLA101 group and 29% in the control group. The rate of transplant-related mortality was 0% and 22%, respectively.
Phase 2 studies of NLA101 in chemotherapy and HSCT recipients are ongoing.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
Low inhibitor rate observed in PUPs with hemophilia A
Researchers have observed a low inhibitor rate in previously untreated patients (PUPs) with severe hemophilia A who received treatment with Octanate®.
The study included 51 PUPs who received octanate, a plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate.
Five of these patients (9.8%) developed FVIII inhibitors, all of whom were receiving on-demand treatment.
The hemostatic efficacy of octanate was rated as “excellent” for 99.6% of all infusions, and tolerability was rated “very good” for 99.98% of infusions.
“We are very excited by the low inhibitor rates and the excellent efficacy and tolerability achieved with octanate® in this particularly challenging patient population,” said Larisa Belyanskaya, head of IBU Haematology at Octapharma AG, the company marketing octanate.
Octapharma sponsored this study, the results of which were published in Haemophilia.
The study enrolled 51 Caucasian males with previously untreated, severe hemophilia A. They had a median age at study entry of 7.7 months (range, 0.1 months to 67.3 months).
Patients received octanate, either prophylactically or on-demand, for 100 exposure days (EDs) or 5 years, whichever came first.
There were a mean of 136.33 (±246.3) EDs, and the mean dose of octanate was 38.4 (±28.6) IU/kg/ED. Most patients (78.4%) had at least 100 EDs. The total number of EDs was 6953.
Prophylaxis accounted for 3027 EDs, immune tolerance induction for 1869 EDs, treatment of bleeds for 1817 EDs, surgical procedures for 149 EDs, and in vivo recovery assessments for 106 EDs.
Inhibitors
Five patients developed FVIII inhibitors, 4 of which were high titer and 1 low titer.
In 3 cases, the inhibitors were considered clinically relevant. In the other 2 cases, the inhibitors disappeared without a change in dose or treatment frequency.
All inhibitors developed during on-demand treatment, and all 4 high-titer inhibitors developed within the first 20 EDs.
All patients who developed inhibitors had major F8 gene defects (intron 22 inversions or large deletions of exons 7-12) that are associated with a high risk of inhibitor development.
Efficacy
The hemostatic efficacy of octanate was rated as “excellent” in 99.6% of infusions (n=4700), “good” in 0.3% (n=15), and “moderate” in 0.02% (n=1).
Most bleeds resolved within 1 day of treatment (81.2%) or within 2 days (14.3%).
Efficacy was rated as “excellent” for all but 1 of the 2611 prophylactic infusions. One was rated as “good.”
For treatment of bleeds, efficacy was rated as “excellent” for 99.2% of infusions (n=1809), “good” for 0.8% (n=14), and “moderate” for 0.05% (n=1).
There were 23 evaluable surgical procedures in 19 patients. The efficacy of octanate was rated as “excellent” in all cases (201 infusions).
Safety
There were 260 treatment-emergent adverse events (AEs) in 45 patients (88.2%). Seventy-eight of these AEs were serious.
Twenty-one AEs were considered probably or possibly related to octanate—asymptomatic parvovirus B19 seroconversions (n=16) and FVIII inhibitor development (n=5). These were classified as serious AEs according to the study protocol.
The tolerability of octanate was considered “very good” in 99.98% of infusions (n=8674) and “good” in 0.02% (n=2).
Researchers have observed a low inhibitor rate in previously untreated patients (PUPs) with severe hemophilia A who received treatment with Octanate®.
The study included 51 PUPs who received octanate, a plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate.
Five of these patients (9.8%) developed FVIII inhibitors, all of whom were receiving on-demand treatment.
The hemostatic efficacy of octanate was rated as “excellent” for 99.6% of all infusions, and tolerability was rated “very good” for 99.98% of infusions.
“We are very excited by the low inhibitor rates and the excellent efficacy and tolerability achieved with octanate® in this particularly challenging patient population,” said Larisa Belyanskaya, head of IBU Haematology at Octapharma AG, the company marketing octanate.
Octapharma sponsored this study, the results of which were published in Haemophilia.
The study enrolled 51 Caucasian males with previously untreated, severe hemophilia A. They had a median age at study entry of 7.7 months (range, 0.1 months to 67.3 months).
Patients received octanate, either prophylactically or on-demand, for 100 exposure days (EDs) or 5 years, whichever came first.
There were a mean of 136.33 (±246.3) EDs, and the mean dose of octanate was 38.4 (±28.6) IU/kg/ED. Most patients (78.4%) had at least 100 EDs. The total number of EDs was 6953.
Prophylaxis accounted for 3027 EDs, immune tolerance induction for 1869 EDs, treatment of bleeds for 1817 EDs, surgical procedures for 149 EDs, and in vivo recovery assessments for 106 EDs.
Inhibitors
Five patients developed FVIII inhibitors, 4 of which were high titer and 1 low titer.
In 3 cases, the inhibitors were considered clinically relevant. In the other 2 cases, the inhibitors disappeared without a change in dose or treatment frequency.
All inhibitors developed during on-demand treatment, and all 4 high-titer inhibitors developed within the first 20 EDs.
All patients who developed inhibitors had major F8 gene defects (intron 22 inversions or large deletions of exons 7-12) that are associated with a high risk of inhibitor development.
Efficacy
The hemostatic efficacy of octanate was rated as “excellent” in 99.6% of infusions (n=4700), “good” in 0.3% (n=15), and “moderate” in 0.02% (n=1).
Most bleeds resolved within 1 day of treatment (81.2%) or within 2 days (14.3%).
Efficacy was rated as “excellent” for all but 1 of the 2611 prophylactic infusions. One was rated as “good.”
For treatment of bleeds, efficacy was rated as “excellent” for 99.2% of infusions (n=1809), “good” for 0.8% (n=14), and “moderate” for 0.05% (n=1).
There were 23 evaluable surgical procedures in 19 patients. The efficacy of octanate was rated as “excellent” in all cases (201 infusions).
Safety
There were 260 treatment-emergent adverse events (AEs) in 45 patients (88.2%). Seventy-eight of these AEs were serious.
Twenty-one AEs were considered probably or possibly related to octanate—asymptomatic parvovirus B19 seroconversions (n=16) and FVIII inhibitor development (n=5). These were classified as serious AEs according to the study protocol.
The tolerability of octanate was considered “very good” in 99.98% of infusions (n=8674) and “good” in 0.02% (n=2).
Researchers have observed a low inhibitor rate in previously untreated patients (PUPs) with severe hemophilia A who received treatment with Octanate®.
The study included 51 PUPs who received octanate, a plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate.
Five of these patients (9.8%) developed FVIII inhibitors, all of whom were receiving on-demand treatment.
The hemostatic efficacy of octanate was rated as “excellent” for 99.6% of all infusions, and tolerability was rated “very good” for 99.98% of infusions.
“We are very excited by the low inhibitor rates and the excellent efficacy and tolerability achieved with octanate® in this particularly challenging patient population,” said Larisa Belyanskaya, head of IBU Haematology at Octapharma AG, the company marketing octanate.
Octapharma sponsored this study, the results of which were published in Haemophilia.
The study enrolled 51 Caucasian males with previously untreated, severe hemophilia A. They had a median age at study entry of 7.7 months (range, 0.1 months to 67.3 months).
Patients received octanate, either prophylactically or on-demand, for 100 exposure days (EDs) or 5 years, whichever came first.
There were a mean of 136.33 (±246.3) EDs, and the mean dose of octanate was 38.4 (±28.6) IU/kg/ED. Most patients (78.4%) had at least 100 EDs. The total number of EDs was 6953.
Prophylaxis accounted for 3027 EDs, immune tolerance induction for 1869 EDs, treatment of bleeds for 1817 EDs, surgical procedures for 149 EDs, and in vivo recovery assessments for 106 EDs.
Inhibitors
Five patients developed FVIII inhibitors, 4 of which were high titer and 1 low titer.
In 3 cases, the inhibitors were considered clinically relevant. In the other 2 cases, the inhibitors disappeared without a change in dose or treatment frequency.
All inhibitors developed during on-demand treatment, and all 4 high-titer inhibitors developed within the first 20 EDs.
All patients who developed inhibitors had major F8 gene defects (intron 22 inversions or large deletions of exons 7-12) that are associated with a high risk of inhibitor development.
Efficacy
The hemostatic efficacy of octanate was rated as “excellent” in 99.6% of infusions (n=4700), “good” in 0.3% (n=15), and “moderate” in 0.02% (n=1).
Most bleeds resolved within 1 day of treatment (81.2%) or within 2 days (14.3%).
Efficacy was rated as “excellent” for all but 1 of the 2611 prophylactic infusions. One was rated as “good.”
For treatment of bleeds, efficacy was rated as “excellent” for 99.2% of infusions (n=1809), “good” for 0.8% (n=14), and “moderate” for 0.05% (n=1).
There were 23 evaluable surgical procedures in 19 patients. The efficacy of octanate was rated as “excellent” in all cases (201 infusions).
Safety
There were 260 treatment-emergent adverse events (AEs) in 45 patients (88.2%). Seventy-eight of these AEs were serious.
Twenty-one AEs were considered probably or possibly related to octanate—asymptomatic parvovirus B19 seroconversions (n=16) and FVIII inhibitor development (n=5). These were classified as serious AEs according to the study protocol.
The tolerability of octanate was considered “very good” in 99.98% of infusions (n=8674) and “good” in 0.02% (n=2).
FDA approves ready-to-use bivalirudin
The US Food and Drug Administration (FDA) has approved a ready-to-use formulation of bivalirudin for use as an anticoagulant in patients undergoing percutaneous coronary intervention.
Baxter International Inc. expects to launch this frozen, premixed formulation of bivalirudin—Bivalirudin in 0.9% Sodium Chloride Injection—in the US early this year.
The product will be available in 2 commonly prescribed dosage forms and strengths: 250 mg of bivalirudin per 50 mL (5 mg/mL) and 500 mg of bivalirudin per 100 mL (5 mg/mL).
This frozen, premixed, ready-to-use bivalirudin makes use of Baxter’s proprietary frozen GALAXY container technology, a non-PVC and non-DEHP system specifically designed to create a ready-to-use format for unstable molecules.
Baxter’s premixed medications are manufactured to current Good Manufacturing Practice regulations established and monitored by the FDA.
The US Food and Drug Administration (FDA) has approved a ready-to-use formulation of bivalirudin for use as an anticoagulant in patients undergoing percutaneous coronary intervention.
Baxter International Inc. expects to launch this frozen, premixed formulation of bivalirudin—Bivalirudin in 0.9% Sodium Chloride Injection—in the US early this year.
The product will be available in 2 commonly prescribed dosage forms and strengths: 250 mg of bivalirudin per 50 mL (5 mg/mL) and 500 mg of bivalirudin per 100 mL (5 mg/mL).
This frozen, premixed, ready-to-use bivalirudin makes use of Baxter’s proprietary frozen GALAXY container technology, a non-PVC and non-DEHP system specifically designed to create a ready-to-use format for unstable molecules.
Baxter’s premixed medications are manufactured to current Good Manufacturing Practice regulations established and monitored by the FDA.
The US Food and Drug Administration (FDA) has approved a ready-to-use formulation of bivalirudin for use as an anticoagulant in patients undergoing percutaneous coronary intervention.
Baxter International Inc. expects to launch this frozen, premixed formulation of bivalirudin—Bivalirudin in 0.9% Sodium Chloride Injection—in the US early this year.
The product will be available in 2 commonly prescribed dosage forms and strengths: 250 mg of bivalirudin per 50 mL (5 mg/mL) and 500 mg of bivalirudin per 100 mL (5 mg/mL).
This frozen, premixed, ready-to-use bivalirudin makes use of Baxter’s proprietary frozen GALAXY container technology, a non-PVC and non-DEHP system specifically designed to create a ready-to-use format for unstable molecules.
Baxter’s premixed medications are manufactured to current Good Manufacturing Practice regulations established and monitored by the FDA.
EC grants orphan designation to gilteritinib for AML
The European Commission (EC) has granted orphan designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication, FLT3 tyrosine kinase domain, and the AXL receptor.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology last June.
The study enrolled 252 adults with relapsed/refractory AML. They received gilteritinib once daily in 1 of 7 dose-escalation (n=23) or dose-expansion (n=229) cohorts.
The maximum tolerated dose was 300 mg/day. There were 2 dose-limiting toxicities in the 450 mg dose-escalation cohort—grade 3 diarrhea and grade 3 elevated aspartate aminotransferase.
Common treatment-related adverse events were diarrhea (37%), anemia (34%), fatigue (33%), elevated aspartate aminotransferase (26%), and increased alanine aminotransferase (19%).
Serious adverse events related to treatment included febrile neutropenia (n=5), sepsis (n=2), acute renal failure (n=5), pyrexia (n=3), and bacteremia (n=1).
There were 7 deaths considered possibly or probably related to treatment—pulmonary embolism (200 mg/day), respiratory failure (120 mg/day), hemoptysis (80 mg/day), intracranial hemorrhage (20 mg/day), ventricular fibrillation (120 mg/day), septic shock (80 mg/day), and neutropenia (120 mg/day).
The overall response rate was 40% (100/249), and the complete response (CR) rate was 8% (n=19).
Four percent of patients (n=10) had a CR with incomplete platelet recovery, 18% (n=46) had a CR with incomplete hematological recovery, and 10% (n=25) had a partial response.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission (EC) has granted orphan designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication, FLT3 tyrosine kinase domain, and the AXL receptor.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology last June.
The study enrolled 252 adults with relapsed/refractory AML. They received gilteritinib once daily in 1 of 7 dose-escalation (n=23) or dose-expansion (n=229) cohorts.
The maximum tolerated dose was 300 mg/day. There were 2 dose-limiting toxicities in the 450 mg dose-escalation cohort—grade 3 diarrhea and grade 3 elevated aspartate aminotransferase.
Common treatment-related adverse events were diarrhea (37%), anemia (34%), fatigue (33%), elevated aspartate aminotransferase (26%), and increased alanine aminotransferase (19%).
Serious adverse events related to treatment included febrile neutropenia (n=5), sepsis (n=2), acute renal failure (n=5), pyrexia (n=3), and bacteremia (n=1).
There were 7 deaths considered possibly or probably related to treatment—pulmonary embolism (200 mg/day), respiratory failure (120 mg/day), hemoptysis (80 mg/day), intracranial hemorrhage (20 mg/day), ventricular fibrillation (120 mg/day), septic shock (80 mg/day), and neutropenia (120 mg/day).
The overall response rate was 40% (100/249), and the complete response (CR) rate was 8% (n=19).
Four percent of patients (n=10) had a CR with incomplete platelet recovery, 18% (n=46) had a CR with incomplete hematological recovery, and 10% (n=25) had a partial response.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Commission (EC) has granted orphan designation to gilteritinib for the treatment of patients with acute myeloid leukemia (AML).
Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication, FLT3 tyrosine kinase domain, and the AXL receptor.
Astellas Pharma Inc. is currently investigating gilteritinib in phase 3 trials of AML patients.
Results from a phase 1/2 study of gilteritinib in AML were published in The Lancet Oncology last June.
The study enrolled 252 adults with relapsed/refractory AML. They received gilteritinib once daily in 1 of 7 dose-escalation (n=23) or dose-expansion (n=229) cohorts.
The maximum tolerated dose was 300 mg/day. There were 2 dose-limiting toxicities in the 450 mg dose-escalation cohort—grade 3 diarrhea and grade 3 elevated aspartate aminotransferase.
Common treatment-related adverse events were diarrhea (37%), anemia (34%), fatigue (33%), elevated aspartate aminotransferase (26%), and increased alanine aminotransferase (19%).
Serious adverse events related to treatment included febrile neutropenia (n=5), sepsis (n=2), acute renal failure (n=5), pyrexia (n=3), and bacteremia (n=1).
There were 7 deaths considered possibly or probably related to treatment—pulmonary embolism (200 mg/day), respiratory failure (120 mg/day), hemoptysis (80 mg/day), intracranial hemorrhage (20 mg/day), ventricular fibrillation (120 mg/day), septic shock (80 mg/day), and neutropenia (120 mg/day).
The overall response rate was 40% (100/249), and the complete response (CR) rate was 8% (n=19).
Four percent of patients (n=10) had a CR with incomplete platelet recovery, 18% (n=46) had a CR with incomplete hematological recovery, and 10% (n=25) had a partial response.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
EC authorizes brentuximab vedotin for CTCL
The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).
The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.
Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.
With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.
Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.
The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:
- Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.
Phase 3 data
The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.
Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.
The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.
Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.
For the update, the median follow-up was 33.9 months.
There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).
The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).
At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).
Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.
In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.
The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).
The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.
Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.
With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.
Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.
The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:
- Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.
Phase 3 data
The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.
Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.
The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.
Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.
For the update, the median follow-up was 33.9 months.
There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).
The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).
At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).
Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.
In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.
The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).
The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.
Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.
With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.
Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.
The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:
- Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.
Phase 3 data
The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.
Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.
The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.
Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.
For the update, the median follow-up was 33.9 months.
There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).
The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).
At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).
Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.
In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.
Ofatumumab to be pulled from non-US markets
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.
The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.
Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.
And Novartis will continue to market ofatumumab for CLL in the US.
“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.
Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.
The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.
About ofatumumab
Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.
In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.
Other approved indications for ofatumumab in the European Union include:
- In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
- In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.
Other approved indications for ofatumumab in the US include:
- In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
- In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
- For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
Health systems plan to produce drugs themselves
A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.
The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.
“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.
“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”
The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).
The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.
“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.
“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”
The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:
- Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
- Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
- Clayton Christensen, professor at Harvard Business School and founder of Innosight
- Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
- Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
- Senior-level leaders from the organizations founding the company.
A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.
The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.
“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.
“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”
The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).
The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.
“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.
“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”
The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:
- Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
- Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
- Clayton Christensen, professor at Harvard Business School and founder of Innosight
- Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
- Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
- Senior-level leaders from the organizations founding the company.
A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.
The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.
“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.
“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”
The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).
The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.
“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.
“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”
The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:
- Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
- Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
- Clayton Christensen, professor at Harvard Business School and founder of Innosight
- Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
- Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
- Senior-level leaders from the organizations founding the company.
FDA grants priority review to daratumumab sBLA
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.
The FDA expects to make a decision on the sBLA by May 21, 2018.
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 grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.
In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.
D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).
D-VMP also prolonged progression-free survival (PFS) compared to VMP.
The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.
The median overall survival was not reached in either treatment arm.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.
There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.
About daratumumab
Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:
- In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
- In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
- As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.
The FDA expects to make a decision on the sBLA by May 21, 2018.
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 grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.
In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.
D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).
D-VMP also prolonged progression-free survival (PFS) compared to VMP.
The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.
The median overall survival was not reached in either treatment arm.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.
There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.
About daratumumab
Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:
- In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
- In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
- As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).
This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.
The FDA expects to make a decision on the sBLA by May 21, 2018.
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 grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.
In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.
D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).
D-VMP also prolonged progression-free survival (PFS) compared to VMP.
The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.
The median overall survival was not reached in either treatment arm.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.
There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.
About daratumumab
Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:
- In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
- In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
- As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
Predicting response to AZA in MDS, CMML
Researchers have developed a technique that may help predict whether patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) will respond to treatment with azacytidine (AZA).
“The new method, called AZA-MS, utilizes a cutting-edge technique known as mass spectrometry to measure the different forms of AZA inside blood cells of patients—such as the AZA molecules that are incorporated into the DNA or RNA,” said Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
With this method, Dr Unnikrishnan and his colleagues found that patients who do not respond to AZA may incorporate fewer AZA molecules in their DNA and have lower DNA demethylation than responders. However, this is not always the case.
The researchers reported these findings in Leukemia.
The team initially tested AZA-MS in AZA-treated RKO cells and found that AZA-MS could quantify the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA, and the cytoplasm—all in the same sample.
The researchers also found that AZA induced dose-dependent DNA demethylation but did not have an effect on RNA methylation.
The team then used AZA-MS to analyze bone marrow samples from patients with MDS (n=4) or CMML (n=4) who were undergoing treatment with AZA. All of the patients had received at least 6 cycles of the drug.
Each patient had 3 bone marrow samples collected—one immediately before starting treatment; one on day 8 of cycle 1 (C1d8); and one on day 28 of cycle 1 (C1d28), when they had spent 20 days off the drug.
Four of the patients were complete responders, and 4 were nonresponders. In each group, 2 patients had MDS, and 2 had CMML.
At C1d8, DNA-5-AZA-CdR was significantly greater in responders than nonresponders. And, overall, responders had increased DNA demethylation compared to nonresponders.
However, the researchers also observed differences among the nonresponders. Two nonresponders had very low levels of DNA-5-AZA-CdR at C1d8 and no demethylation. The other 2 nonresponders had much higher DNA-5-AZA-CdR and DNA demethylation levels, which were comparable to levels in responders.
The researchers said they could detect AZA and DNA-5-AZA-CdR intracellularly, as well as RNA-AZA, in the nonresponders with minimal DNA-5-AZA-CdR and DNA demethylation.
The team said this suggests that neither cellular uptake nor intracellular metabolism explain the low DNA-5-AZA-CdR in these patients. Instead, the researchers believe these patients may have a greater proportion of bone marrow cells that are quiescent and not undergoing DNA replication.
The researchers also believe the nonresponders with higher DNA-5-AZA-CdR may be explained by a failure to induce an interferon response, which is necessary for a clinical response.
On the other hand, these nonresponders could have defective immune cell-mediated clearance of dysplastic cells or increased tolerance to this clearance, the researchers said.
The team also noted that, at C1d28, DNA-5-AZA-CdR levels dropped (but were still detectable) in all 8 patients, and DNA methylation had nearly returned to pretreatment levels in all patients.
Researchers have developed a technique that may help predict whether patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) will respond to treatment with azacytidine (AZA).
“The new method, called AZA-MS, utilizes a cutting-edge technique known as mass spectrometry to measure the different forms of AZA inside blood cells of patients—such as the AZA molecules that are incorporated into the DNA or RNA,” said Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
With this method, Dr Unnikrishnan and his colleagues found that patients who do not respond to AZA may incorporate fewer AZA molecules in their DNA and have lower DNA demethylation than responders. However, this is not always the case.
The researchers reported these findings in Leukemia.
The team initially tested AZA-MS in AZA-treated RKO cells and found that AZA-MS could quantify the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA, and the cytoplasm—all in the same sample.
The researchers also found that AZA induced dose-dependent DNA demethylation but did not have an effect on RNA methylation.
The team then used AZA-MS to analyze bone marrow samples from patients with MDS (n=4) or CMML (n=4) who were undergoing treatment with AZA. All of the patients had received at least 6 cycles of the drug.
Each patient had 3 bone marrow samples collected—one immediately before starting treatment; one on day 8 of cycle 1 (C1d8); and one on day 28 of cycle 1 (C1d28), when they had spent 20 days off the drug.
Four of the patients were complete responders, and 4 were nonresponders. In each group, 2 patients had MDS, and 2 had CMML.
At C1d8, DNA-5-AZA-CdR was significantly greater in responders than nonresponders. And, overall, responders had increased DNA demethylation compared to nonresponders.
However, the researchers also observed differences among the nonresponders. Two nonresponders had very low levels of DNA-5-AZA-CdR at C1d8 and no demethylation. The other 2 nonresponders had much higher DNA-5-AZA-CdR and DNA demethylation levels, which were comparable to levels in responders.
The researchers said they could detect AZA and DNA-5-AZA-CdR intracellularly, as well as RNA-AZA, in the nonresponders with minimal DNA-5-AZA-CdR and DNA demethylation.
The team said this suggests that neither cellular uptake nor intracellular metabolism explain the low DNA-5-AZA-CdR in these patients. Instead, the researchers believe these patients may have a greater proportion of bone marrow cells that are quiescent and not undergoing DNA replication.
The researchers also believe the nonresponders with higher DNA-5-AZA-CdR may be explained by a failure to induce an interferon response, which is necessary for a clinical response.
On the other hand, these nonresponders could have defective immune cell-mediated clearance of dysplastic cells or increased tolerance to this clearance, the researchers said.
The team also noted that, at C1d28, DNA-5-AZA-CdR levels dropped (but were still detectable) in all 8 patients, and DNA methylation had nearly returned to pretreatment levels in all patients.
Researchers have developed a technique that may help predict whether patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) will respond to treatment with azacytidine (AZA).
“The new method, called AZA-MS, utilizes a cutting-edge technique known as mass spectrometry to measure the different forms of AZA inside blood cells of patients—such as the AZA molecules that are incorporated into the DNA or RNA,” said Ashwin Unnikrishnan, PhD, of the University of New South Wales in Sydney, Australia.
With this method, Dr Unnikrishnan and his colleagues found that patients who do not respond to AZA may incorporate fewer AZA molecules in their DNA and have lower DNA demethylation than responders. However, this is not always the case.
The researchers reported these findings in Leukemia.
The team initially tested AZA-MS in AZA-treated RKO cells and found that AZA-MS could quantify the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA, and the cytoplasm—all in the same sample.
The researchers also found that AZA induced dose-dependent DNA demethylation but did not have an effect on RNA methylation.
The team then used AZA-MS to analyze bone marrow samples from patients with MDS (n=4) or CMML (n=4) who were undergoing treatment with AZA. All of the patients had received at least 6 cycles of the drug.
Each patient had 3 bone marrow samples collected—one immediately before starting treatment; one on day 8 of cycle 1 (C1d8); and one on day 28 of cycle 1 (C1d28), when they had spent 20 days off the drug.
Four of the patients were complete responders, and 4 were nonresponders. In each group, 2 patients had MDS, and 2 had CMML.
At C1d8, DNA-5-AZA-CdR was significantly greater in responders than nonresponders. And, overall, responders had increased DNA demethylation compared to nonresponders.
However, the researchers also observed differences among the nonresponders. Two nonresponders had very low levels of DNA-5-AZA-CdR at C1d8 and no demethylation. The other 2 nonresponders had much higher DNA-5-AZA-CdR and DNA demethylation levels, which were comparable to levels in responders.
The researchers said they could detect AZA and DNA-5-AZA-CdR intracellularly, as well as RNA-AZA, in the nonresponders with minimal DNA-5-AZA-CdR and DNA demethylation.
The team said this suggests that neither cellular uptake nor intracellular metabolism explain the low DNA-5-AZA-CdR in these patients. Instead, the researchers believe these patients may have a greater proportion of bone marrow cells that are quiescent and not undergoing DNA replication.
The researchers also believe the nonresponders with higher DNA-5-AZA-CdR may be explained by a failure to induce an interferon response, which is necessary for a clinical response.
On the other hand, these nonresponders could have defective immune cell-mediated clearance of dysplastic cells or increased tolerance to this clearance, the researchers said.
The team also noted that, at C1d28, DNA-5-AZA-CdR levels dropped (but were still detectable) in all 8 patients, and DNA methylation had nearly returned to pretreatment levels in all patients.
Bright light therapy improves sleep in cancer survivors
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.
Results of a pilot study suggest that systematic bright light exposure can improve sleep in fatigued cancer survivors.
Subjects who were exposed to bright light every morning for 4 weeks had a significantly greater improvement in sleep efficiency than those who were exposed to dim light over the same period.
In fact, subjects in the bright light group were able to achieve clinically normal levels of sleep efficiency, and subjects in the dim light group were not.
Sleep efficiency is the percentage of time in bed that subjects spent sleeping.
Lisa M. Wu, PhD, of Northwestern University in Chicago, Illinois, and her colleagues reported these results in the Journal of Clinical Sleep Medicine.
The team noted that cancer patients report sleep disturbances at a significantly higher rate than the general population. Between 23% and 44% of cancer patients experience insomnia symptoms even years after treatment.
With this in mind, the researchers studied 44 individuals who had completed cancer treatment and met criteria for clinically significant fatigue at screening.
The subjects had an average age of 53.6, and 75% percent were female. Roughly 55% (n=24) had been diagnosed with a hematologic malignancy.
The subjects were randomized to a bright white light intervention or a dim red light intervention. Subjects in both treatment arms were provided with a light box and instructed to use it every morning for 30 minutes for 4 weeks. Sleep was evaluated using wrist actigraphy and the Pittsburgh Sleep Quality Index.
At baseline, 52.6% of subjects in the dim light group and 60% in the bright light group exceeded the clinical cutoff for poor sleep efficiency (≤ 85%). The mean sleep efficiency was 81.8% and 82.8%, respectively.
During the study period, sleep efficiency improved significantly more among subjects exposed to the bright light than those exposed to the dim light (P=0.003).
The mean sleep efficiency was in the clinically normal range for subjects in the bright light group at the end of the intervention (86.06%) and 3 weeks after (85.77%).
However, the cutoff for poor sleep efficiency was not reached in the dim light group, either at the end of the intervention (mean=79.35%) or 3 weeks after (mean=80.88%).
Total sleep time tended to increase over the study period for subjects in the bright light group, but there was no significant difference in total sleep time between the bright light and dim light groups.
Likewise, there was no significant between-group difference in waking after sleep onset, although this outcome tended to decrease over the study period for subjects in the bright light group.
“Systematic light exposure using bright white light is a low-cost and easily disseminated intervention that offers a feasible and potentially effective alternative to improve sleep in cancer survivors,” Dr Wu said.
However, she and her colleagues noted that larger-scale studies are needed.