Pharmacy

Drug production

Credit: FDA

The US Food and Drug Administration (FDA) has approved the oral, direct factor Xa inhibitor edoxaban (Savaysa) for use in two patient populations.

The anticoagulant is now approved to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and to treat venous thromboembolism (VTE) in patients who have already received parenteral anticoagulation for 5 to 10 days.

The drug has been approved with a Boxed Warning.

The warning states that edoxaban is less effective in NVAF patients with a creatinine clearance greater than 95 mL/min. Patients with creatinine clearance above this limit have an increased risk of stroke if they receive edoxaban (compared to the risk with warfarin), so these patients should not receive edoxaban.

The warning also states that premature discontinuation of edoxaban increases the risk of stroke. Furthermore, spinal or epidural hematomas may occur in patients on edoxaban who are receiving anesthesia injected around the spine or undergoing spinal puncture.

Edoxaban for VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with deep vein thrombosis and 3319 with pulmonary embolism. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

Edoxaban proved superior when it came to the primary safety outcome. Clinically relevant bleeding occurred in 8.5% of edoxaban-treated patients and 10.3% of warfarin-treated patients (P=0.004 for superiority).

In the edoxaban arm, there were 2 fatal bleeds and 13 non-fatal bleeds in a critical site. With warfarin, there were 10 fatal bleeds and 25 non-fatal bleeds in a critical site.

Edoxaban in NVAF

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or SEE was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

Annualized rates for the secondary composite endpoint of stroke, SEE, and cardiovascular death were 4.43% with warfarin, 3.85% with edoxaban at 60 mg (P=0.005), and 4.23% with edoxaban at 30 mg (P=0.32).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Edoxaban is under development by Daiichi Sankyo Co., Ltd.

Drug production

Credit: FDA

The US Food and Drug Administration (FDA) has approved the oral, direct factor Xa inhibitor edoxaban (Savaysa) for use in two patient populations.

The anticoagulant is now approved to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and to treat venous thromboembolism (VTE) in patients who have already received parenteral anticoagulation for 5 to 10 days.

The drug has been approved with a Boxed Warning.

The warning states that edoxaban is less effective in NVAF patients with a creatinine clearance greater than 95 mL/min. Patients with creatinine clearance above this limit have an increased risk of stroke if they receive edoxaban (compared to the risk with warfarin), so these patients should not receive edoxaban.

The warning also states that premature discontinuation of edoxaban increases the risk of stroke. Furthermore, spinal or epidural hematomas may occur in patients on edoxaban who are receiving anesthesia injected around the spine or undergoing spinal puncture.

Edoxaban for VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with deep vein thrombosis and 3319 with pulmonary embolism. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

Edoxaban proved superior when it came to the primary safety outcome. Clinically relevant bleeding occurred in 8.5% of edoxaban-treated patients and 10.3% of warfarin-treated patients (P=0.004 for superiority).

In the edoxaban arm, there were 2 fatal bleeds and 13 non-fatal bleeds in a critical site. With warfarin, there were 10 fatal bleeds and 25 non-fatal bleeds in a critical site.

Edoxaban in NVAF

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or SEE was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

Annualized rates for the secondary composite endpoint of stroke, SEE, and cardiovascular death were 4.43% with warfarin, 3.85% with edoxaban at 60 mg (P=0.005), and 4.23% with edoxaban at 30 mg (P=0.32).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Edoxaban is under development by Daiichi Sankyo Co., Ltd.

Drug production

Credit: FDA

The US Food and Drug Administration (FDA) has approved the oral, direct factor Xa inhibitor edoxaban (Savaysa) for use in two patient populations.

The anticoagulant is now approved to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and to treat venous thromboembolism (VTE) in patients who have already received parenteral anticoagulation for 5 to 10 days.

The drug has been approved with a Boxed Warning.

The warning states that edoxaban is less effective in NVAF patients with a creatinine clearance greater than 95 mL/min. Patients with creatinine clearance above this limit have an increased risk of stroke if they receive edoxaban (compared to the risk with warfarin), so these patients should not receive edoxaban.

The warning also states that premature discontinuation of edoxaban increases the risk of stroke. Furthermore, spinal or epidural hematomas may occur in patients on edoxaban who are receiving anesthesia injected around the spine or undergoing spinal puncture.

Edoxaban for VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with deep vein thrombosis and 3319 with pulmonary embolism. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

Edoxaban proved superior when it came to the primary safety outcome. Clinically relevant bleeding occurred in 8.5% of edoxaban-treated patients and 10.3% of warfarin-treated patients (P=0.004 for superiority).

In the edoxaban arm, there were 2 fatal bleeds and 13 non-fatal bleeds in a critical site. With warfarin, there were 10 fatal bleeds and 25 non-fatal bleeds in a critical site.

Edoxaban in NVAF

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or SEE was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

Annualized rates for the secondary composite endpoint of stroke, SEE, and cardiovascular death were 4.43% with warfarin, 3.85% with edoxaban at 60 mg (P=0.005), and 4.23% with edoxaban at 30 mg (P=0.32).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Edoxaban is under development by Daiichi Sankyo Co., Ltd.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to SGX301 as a first-line treatment for cutaneous T-cell lymphoma (CTCL).

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is set to begin in the first half of this year. In addition to its new fast track status, SGX301 also has orphan designation from the FDA.

About fast track designation

The FDA grants fast track designation to a drug that is intended to treat a serious or life-threatening condition and that demonstrates the potential to address an unmet medical need for the condition.

Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, Soligenix, Inc., the company developing SGX301, is eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, allowing the FDA to review sections of the NDA prior to receiving the complete submission.

Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately 6 months.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan drug designation to treat multiple myeloma (MM).

Selinexor already has orphan designation from the FDA to treat acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL).

The drug has also received orphan designation from the European Medicines Agency (EMA) to treat MM, AML, DLBCL, and chronic lymphocytic leukemia/small lymphocytic lymphoma, including Richter’s transformation.

“Orphan drug designation by the FDA for multiple myeloma is another significant milestone in the selinexor development program,” said Sharon Shacham, PhD, President and Chief Scientific Officer of Karyopharm Therapeutics, Inc., the company developing selinexor.

In the US, orphan designation qualifies a company for certain benefits, including an accelerated approval process, 7 years of market exclusivity following the drug’s approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

About selinexor

Selinexor (KPT-330) is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

Selinexor combos in MM

In a poster presented at the 2014 ASH Annual Meeting (4773), researchers reported results observed with selinexor plus dexamethasone in preclinical models and in patients with heavily pretreated, refractory MM.

The study included 9 evaluable patients who received selinexor at 45 mg/m² twice weekly and dexamethasone at 20 mg twice weekly. The combination prompted an overall response rate of 67%, with one stringent complete response (11%) and 5 partial responses (56%), as well as a clinical benefit rate of 89%.

The combination demonstrated a reduction in nausea grades and very little weight loss compared with selinexor alone. The most common grade 1/2 adverse events were nausea, fatigue, anorexia, and vomiting.

The combination was also associated with an increase in time on study relative to selinexor alone. Sixty-six percent of patients remained on study for at least 16 weeks, including one patient for 28 weeks and one for 43 weeks as of December 1, 2014.

During the dose-evaluation part of the study, the 60 mg/m² selinexor dose was deemed intolerable in this heavily pretreated patient population. So 45 mg/m² is the recommended future study dose.

In another poster presented at the 2014 ASH Annual Meeting (3443), researchers described the activity of selinexor in combination with carfilzomib. This preclinical study revealed a novel, intracellular, membrane-embedded mechanism of caspase activation.

The results suggested a model of synergy wherein the selinexor-carfilzomib combination promotes caspase activation, likely by induced proximity, cleavage of other caspases, and subsequent apoptosis as well as autophagy.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan drug designation to treat multiple myeloma (MM).

Selinexor already has orphan designation from the FDA to treat acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL).

The drug has also received orphan designation from the European Medicines Agency (EMA) to treat MM, AML, DLBCL, and chronic lymphocytic leukemia/small lymphocytic lymphoma, including Richter’s transformation.

“Orphan drug designation by the FDA for multiple myeloma is another significant milestone in the selinexor development program,” said Sharon Shacham, PhD, President and Chief Scientific Officer of Karyopharm Therapeutics, Inc., the company developing selinexor.

In the US, orphan designation qualifies a company for certain benefits, including an accelerated approval process, 7 years of market exclusivity following the drug’s approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

About selinexor

Selinexor (KPT-330) is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

Selinexor combos in MM

In a poster presented at the 2014 ASH Annual Meeting (4773), researchers reported results observed with selinexor plus dexamethasone in preclinical models and in patients with heavily pretreated, refractory MM.

The study included 9 evaluable patients who received selinexor at 45 mg/m² twice weekly and dexamethasone at 20 mg twice weekly. The combination prompted an overall response rate of 67%, with one stringent complete response (11%) and 5 partial responses (56%), as well as a clinical benefit rate of 89%.

The combination demonstrated a reduction in nausea grades and very little weight loss compared with selinexor alone. The most common grade 1/2 adverse events were nausea, fatigue, anorexia, and vomiting.

The combination was also associated with an increase in time on study relative to selinexor alone. Sixty-six percent of patients remained on study for at least 16 weeks, including one patient for 28 weeks and one for 43 weeks as of December 1, 2014.

During the dose-evaluation part of the study, the 60 mg/m² selinexor dose was deemed intolerable in this heavily pretreated patient population. So 45 mg/m² is the recommended future study dose.

In another poster presented at the 2014 ASH Annual Meeting (3443), researchers described the activity of selinexor in combination with carfilzomib. This preclinical study revealed a novel, intracellular, membrane-embedded mechanism of caspase activation.

The results suggested a model of synergy wherein the selinexor-carfilzomib combination promotes caspase activation, likely by induced proximity, cleavage of other caspases, and subsequent apoptosis as well as autophagy.

Micrograph showing MM

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan drug designation to treat multiple myeloma (MM).

Selinexor already has orphan designation from the FDA to treat acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL).

The drug has also received orphan designation from the European Medicines Agency (EMA) to treat MM, AML, DLBCL, and chronic lymphocytic leukemia/small lymphocytic lymphoma, including Richter’s transformation.

“Orphan drug designation by the FDA for multiple myeloma is another significant milestone in the selinexor development program,” said Sharon Shacham, PhD, President and Chief Scientific Officer of Karyopharm Therapeutics, Inc., the company developing selinexor.

In the US, orphan designation qualifies a company for certain benefits, including an accelerated approval process, 7 years of market exclusivity following the drug’s approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

About selinexor

Selinexor (KPT-330) is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

Selinexor combos in MM

In a poster presented at the 2014 ASH Annual Meeting (4773), researchers reported results observed with selinexor plus dexamethasone in preclinical models and in patients with heavily pretreated, refractory MM.

The study included 9 evaluable patients who received selinexor at 45 mg/m² twice weekly and dexamethasone at 20 mg twice weekly. The combination prompted an overall response rate of 67%, with one stringent complete response (11%) and 5 partial responses (56%), as well as a clinical benefit rate of 89%.

The combination demonstrated a reduction in nausea grades and very little weight loss compared with selinexor alone. The most common grade 1/2 adverse events were nausea, fatigue, anorexia, and vomiting.

The combination was also associated with an increase in time on study relative to selinexor alone. Sixty-six percent of patients remained on study for at least 16 weeks, including one patient for 28 weeks and one for 43 weeks as of December 1, 2014.

During the dose-evaluation part of the study, the 60 mg/m² selinexor dose was deemed intolerable in this heavily pretreated patient population. So 45 mg/m² is the recommended future study dose.

In another poster presented at the 2014 ASH Annual Meeting (3443), researchers described the activity of selinexor in combination with carfilzomib. This preclinical study revealed a novel, intracellular, membrane-embedded mechanism of caspase activation.

The results suggested a model of synergy wherein the selinexor-carfilzomib combination promotes caspase activation, likely by induced proximity, cleavage of other caspases, and subsequent apoptosis as well as autophagy.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation 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.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation 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.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

Blood collection

Credit: Charles Haymond

The European Commission has granted KTE-C19, a chimeric antigen receptor (CAR) T-cell therapy, orphan designation to treat patients with diffuse large B-cell lymphoma (DLBCL) in the European Union (EU).

To create KTE-C19, a patient’s T cells are genetically modified using a gammaretroviral vector to express a CAR designed to target CD19, a protein expressed on B cells.

The product received orphan designation to treat DLBCL in the US last March.

“We are pleased with the approval of orphan drug designation for KTE-C19 in the EU, another important milestone for Kite Pharma and for the progress of our lead program,” said Arie Belldegrun, MD, President and CEO of Kite Pharma, Inc., the company developing KTE-C19.

Orphan designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 persons in the EU, and where no satisfactory treatment is available.

In addition to a 10-year period of marketing exclusivity in the EU after product approval, orphan drug designation 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.

KTE-C19 in DLBCL

In a study published in the Journal of Clinical Oncology last year, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.

The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.

Of the 7 patients with chemotherapy-refractory DLBCL, 4 achieved a complete response to treatment, 2 achieved a partial response, and 1 had stable disease. Three of the complete responses were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.

In the entire patient population, KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.

Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.

For more information on KTE-C19, visit Kite Pharma’s website.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, for the treatment of Waldenström’s macroglobulinemia (WM).

The designation provides the drug’s maker, Idera Pharmaceuticals, with certain incentives, including eligibility for federal grants, research and development tax credits, and 7 years of marketing exclusivity if the product is approved.

Preclinical studies have shown that, in WM and other B‐cell lymphomas characterized by the MYD88 L265P oncogenic mutation, TLR signaling is overactivated. And this enables tumor cell survival and proliferation.

About 90% of WM patients are reported to harbor the MYD88 L265P mutation.

In research presented at the 2014 AACR Annual Meeting, investigators showed that IMO-8400 decreased the viability of mutated WM cells and diffuse large B-cell lymphoma (DLBCL) cells in vitro. The drug also decreased tumor growth and prolonged survival in mice with MYD88 L265P-positive DLBCL.

Now, Idera is conducting a phase 1/2 trial (NCT02092909) of IMO-8400 in patients with WM who have a history of relapse or failure to respond to one or more prior therapies. The protocol includes 3 dose-escalation cohorts of IMO-8400 administered subcutaneously.

The trial’s independent data review committee has completed its review of 4-week safety data from the second dose cohort (1.2 mg/kg/week) and has determined that Idera may open enrollment in the third dose cohort (2.4 mg/kg/week).

Final 24-week safety and clinical activity data are anticipated in the second half of 2015.

Aside from WM, Idera is pursuing clinical development of IMO-8400 in DLBCL patients harboring the MYD88 L265P mutation and in rare autoimmune diseases, including dermatomyositis.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, for the treatment of Waldenström’s macroglobulinemia (WM).

The designation provides the drug’s maker, Idera Pharmaceuticals, with certain incentives, including eligibility for federal grants, research and development tax credits, and 7 years of marketing exclusivity if the product is approved.

Preclinical studies have shown that, in WM and other B‐cell lymphomas characterized by the MYD88 L265P oncogenic mutation, TLR signaling is overactivated. And this enables tumor cell survival and proliferation.

About 90% of WM patients are reported to harbor the MYD88 L265P mutation.

In research presented at the 2014 AACR Annual Meeting, investigators showed that IMO-8400 decreased the viability of mutated WM cells and diffuse large B-cell lymphoma (DLBCL) cells in vitro. The drug also decreased tumor growth and prolonged survival in mice with MYD88 L265P-positive DLBCL.

Now, Idera is conducting a phase 1/2 trial (NCT02092909) of IMO-8400 in patients with WM who have a history of relapse or failure to respond to one or more prior therapies. The protocol includes 3 dose-escalation cohorts of IMO-8400 administered subcutaneously.

The trial’s independent data review committee has completed its review of 4-week safety data from the second dose cohort (1.2 mg/kg/week) and has determined that Idera may open enrollment in the third dose cohort (2.4 mg/kg/week).

Final 24-week safety and clinical activity data are anticipated in the second half of 2015.

Aside from WM, Idera is pursuing clinical development of IMO-8400 in DLBCL patients harboring the MYD88 L265P mutation and in rare autoimmune diseases, including dermatomyositis.

Micrograph showing WM

The US Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, for the treatment of Waldenström’s macroglobulinemia (WM).

The designation provides the drug’s maker, Idera Pharmaceuticals, with certain incentives, including eligibility for federal grants, research and development tax credits, and 7 years of marketing exclusivity if the product is approved.

Preclinical studies have shown that, in WM and other B‐cell lymphomas characterized by the MYD88 L265P oncogenic mutation, TLR signaling is overactivated. And this enables tumor cell survival and proliferation.

About 90% of WM patients are reported to harbor the MYD88 L265P mutation.

In research presented at the 2014 AACR Annual Meeting, investigators showed that IMO-8400 decreased the viability of mutated WM cells and diffuse large B-cell lymphoma (DLBCL) cells in vitro. The drug also decreased tumor growth and prolonged survival in mice with MYD88 L265P-positive DLBCL.

Now, Idera is conducting a phase 1/2 trial (NCT02092909) of IMO-8400 in patients with WM who have a history of relapse or failure to respond to one or more prior therapies. The protocol includes 3 dose-escalation cohorts of IMO-8400 administered subcutaneously.

The trial’s independent data review committee has completed its review of 4-week safety data from the second dose cohort (1.2 mg/kg/week) and has determined that Idera may open enrollment in the third dose cohort (2.4 mg/kg/week).

Final 24-week safety and clinical activity data are anticipated in the second half of 2015.

Aside from WM, Idera is pursuing clinical development of IMO-8400 in DLBCL patients harboring the MYD88 L265P mutation and in rare autoimmune diseases, including dermatomyositis.

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved a supplemental biologics license application for obinutuzumab (Gazyva) in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

The approval adds to the drug’s label data from stage 2 of the CLL11 study, which showed that obinutuzumab plus chlorambucil offers significant clinical improvements when compared head-to-head with rituximab plus chlorambucil.

This includes progression-free survival (PFS), complete response (CR), and minimal residual disease (MRD) data from stage 2 of the study. In addition, overall survival data was added from stage 1, in which researchers compared obinutuzumab plus chlorambucil to chlorambucil alone.

The label now reflects that obinutuzumab plus chlorambucil improved PFS compared to rituximab plus chlorambucil. The median PFS was 26.7 months and 14.9 months, respectively (hazard ratio=0.42, P<0.0001).

Additionally, obinutuzumab plus chlorambucil nearly tripled the CR rate when compared to rituximab plus chlorambucil. The CR rates were 26.1% and 8.8%, respectively.

Of the patients who achieved a CR with or without complete recovery from abnormal blood cell counts, 19% (18/94) of patients in the obinutuzumab arm and 6% (2/34) in the rituximab arm were MRD negative in the bone marrow.

Forty-one percent (39/94) of patients in the obinutuzumab arm and 12% (4/34) in the rituximab arm were MRD-negative in the peripheral blood.

At nearly 2 years, the rate of death was 9% (22/238) for patients who received obinutuzumab plus chlorambucil and 20% (24/118) for those who received chlorambucil alone (hazard ratio=0.41). The median overall survival has not yet been reached.

About obinutuzumab

Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20 on B cells. The drug attacks targeted cells both directly and together with the body’s immune system.

The prescribing information for obinutuzumab includes warnings that the drug can cause serious or life-threatening side effects. These include hepatitis B reactivation, progressive multifocal leukoencephalopathy, infusion reactions, tumor lysis syndrome, infections, and neutropenia.

The most common side effects of the drug are infusion reactions, neutropenia, thrombocytopenia, anemia, fever, cough, nausea, and diarrhea.

Obinutuzumab was FDA-approved for use in combination with chlorambucil to treat previously untreated CLL in November 2013. The drug (which is known as Gazyvaro in Europe) was approved by the European Commission for the same indication in July 2014.

Obinutuzumab was discovered by Roche Glycart AG, an independent research unit of Roche. In the US, the drug is part of a collaboration between Genentech and Biogen Idec.

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved a supplemental biologics license application for obinutuzumab (Gazyva) in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

The approval adds to the drug’s label data from stage 2 of the CLL11 study, which showed that obinutuzumab plus chlorambucil offers significant clinical improvements when compared head-to-head with rituximab plus chlorambucil.

This includes progression-free survival (PFS), complete response (CR), and minimal residual disease (MRD) data from stage 2 of the study. In addition, overall survival data was added from stage 1, in which researchers compared obinutuzumab plus chlorambucil to chlorambucil alone.

The label now reflects that obinutuzumab plus chlorambucil improved PFS compared to rituximab plus chlorambucil. The median PFS was 26.7 months and 14.9 months, respectively (hazard ratio=0.42, P<0.0001).

Additionally, obinutuzumab plus chlorambucil nearly tripled the CR rate when compared to rituximab plus chlorambucil. The CR rates were 26.1% and 8.8%, respectively.

Of the patients who achieved a CR with or without complete recovery from abnormal blood cell counts, 19% (18/94) of patients in the obinutuzumab arm and 6% (2/34) in the rituximab arm were MRD negative in the bone marrow.

Forty-one percent (39/94) of patients in the obinutuzumab arm and 12% (4/34) in the rituximab arm were MRD-negative in the peripheral blood.

At nearly 2 years, the rate of death was 9% (22/238) for patients who received obinutuzumab plus chlorambucil and 20% (24/118) for those who received chlorambucil alone (hazard ratio=0.41). The median overall survival has not yet been reached.

About obinutuzumab

Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20 on B cells. The drug attacks targeted cells both directly and together with the body’s immune system.

The prescribing information for obinutuzumab includes warnings that the drug can cause serious or life-threatening side effects. These include hepatitis B reactivation, progressive multifocal leukoencephalopathy, infusion reactions, tumor lysis syndrome, infections, and neutropenia.

The most common side effects of the drug are infusion reactions, neutropenia, thrombocytopenia, anemia, fever, cough, nausea, and diarrhea.

Obinutuzumab was FDA-approved for use in combination with chlorambucil to treat previously untreated CLL in November 2013. The drug (which is known as Gazyvaro in Europe) was approved by the European Commission for the same indication in July 2014.

Obinutuzumab was discovered by Roche Glycart AG, an independent research unit of Roche. In the US, the drug is part of a collaboration between Genentech and Biogen Idec.

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved a supplemental biologics license application for obinutuzumab (Gazyva) in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

The approval adds to the drug’s label data from stage 2 of the CLL11 study, which showed that obinutuzumab plus chlorambucil offers significant clinical improvements when compared head-to-head with rituximab plus chlorambucil.

This includes progression-free survival (PFS), complete response (CR), and minimal residual disease (MRD) data from stage 2 of the study. In addition, overall survival data was added from stage 1, in which researchers compared obinutuzumab plus chlorambucil to chlorambucil alone.

The label now reflects that obinutuzumab plus chlorambucil improved PFS compared to rituximab plus chlorambucil. The median PFS was 26.7 months and 14.9 months, respectively (hazard ratio=0.42, P<0.0001).

Additionally, obinutuzumab plus chlorambucil nearly tripled the CR rate when compared to rituximab plus chlorambucil. The CR rates were 26.1% and 8.8%, respectively.

Of the patients who achieved a CR with or without complete recovery from abnormal blood cell counts, 19% (18/94) of patients in the obinutuzumab arm and 6% (2/34) in the rituximab arm were MRD negative in the bone marrow.

Forty-one percent (39/94) of patients in the obinutuzumab arm and 12% (4/34) in the rituximab arm were MRD-negative in the peripheral blood.

At nearly 2 years, the rate of death was 9% (22/238) for patients who received obinutuzumab plus chlorambucil and 20% (24/118) for those who received chlorambucil alone (hazard ratio=0.41). The median overall survival has not yet been reached.

About obinutuzumab

Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20 on B cells. The drug attacks targeted cells both directly and together with the body’s immune system.

The prescribing information for obinutuzumab includes warnings that the drug can cause serious or life-threatening side effects. These include hepatitis B reactivation, progressive multifocal leukoencephalopathy, infusion reactions, tumor lysis syndrome, infections, and neutropenia.

The most common side effects of the drug are infusion reactions, neutropenia, thrombocytopenia, anemia, fever, cough, nausea, and diarrhea.

Obinutuzumab was FDA-approved for use in combination with chlorambucil to treat previously untreated CLL in November 2013. The drug (which is known as Gazyvaro in Europe) was approved by the European Commission for the same indication in July 2014.

Obinutuzumab was discovered by Roche Glycart AG, an independent research unit of Roche. In the US, the drug is part of a collaboration between Genentech and Biogen Idec.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

The US Food and Drug Administration (FDA) has approved tbo-filgrastim (Granix) injection for administration by patients and caregivers, allowing physicians to prescribe the drug for in-office or at-home use.

Tbo-filgrastim is a leukocyte growth factor used to reduce the duration of severe neutropenia in patients with non-myeloid malignancies who are receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

The drug has been commercially available in the US since November 2013, but, at present, it can only be administered by a healthcare professional.

Teva Pharmaceutical Industries, Ltd., the company developing tbo-filgrastim, plans to launch the new syringe for administration by patients and caregivers in early 2015.

Clinical trials

Researchers evaluated tbo-filgrastim in 3 phase 3 trials of patients receiving myelosuppressive chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).

In the NHL study, investigators compared tbo-filgrastim to filgrastim for the prevention of chemotherapy-induced neutropenia in 92 patients.

For cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/day) of tbo-filgrastim (n=63) or filgrastim (n=29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.9 days in the filgrastim arm (P=0.1055). The incidence of febrile neutropenia was 11.1% and 20.7%, respectively (P=0.1232).

In the lung cancer trial, researchers compared tbo-filgrastim to filgrastim in 240 patients receiving platinum-based chemotherapy. In cycle 1, patients were randomized to daily injections (subcutaneous 5 µg/kg/d) of tbo-filgrastim  (n=160) or filgrastim (n=80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received tbo-filgrastim.

In cycle 1, the mean duration of severe neutropenia was 0.5 days in the tbo-filgrastim arm and 0.3 days in the filgrastim arm. There was no significant difference in the incidence of febrile neutropenia in cycle 1 between the two arms (P=0.2347).

In the breast cancer trial, investigators compared tbo-filgrastim to filgrastim or placebo in 348 patients receiving chemotherapy. Patients were randomized to daily injections (subcutaneous 5 µg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of tbo-filgrastim (n=140), filgrastim (n=136), or placebo (n=72).

The mean duration of severe neutropenia in cycle 1 was 1.1 days in the tbo-filgrastim arm, 1.1 days in the filgrastim arm, and 3.9 days in the placebo arm.

In all the trials, bone pain was the most frequent treatment-emergent adverse event, occurring in at least 1% of patients treated with tbo-filgrastim at the recommended dose. The overall incidence of bone pain in cycle 1 was 3.4% for tbo-filgrastim, 1.4% for placebo, and 7.5% for filgrastim.

According to the drug’s prescribing information, tbo-filgrastim may pose a risk of splenic rupture, acute respiratory distress syndrome, serious allergic reactions, severe and sometimes fatal sickle cell crises, and capillary leak syndrome. The possibility that the drug acts as a growth factor for tumors cannot be excluded.

Vials of drug

Credit: Bill Branson

Hospira, Inc. has initiated a worldwide, user-level recall of 10 lots of Mitoxantrone (both human and veterinary) due to confirmed subpotency and elevated impurity levels.

Drugs in the affected lots may exhibit decreased effectiveness, require additional dosing, or prompt cumulative impurity toxicity requiring medical intervention.

However, Hospira has not received reports of any adverse events associated with subpotency and impurities for these lots to date.

The lots were distributed to hospitals and veterinary clinics worldwide from February 2013 through November 2014.

The following lots are affected by the recall. (To ensure this list displays properly, click the “Hide” icon on the right side of this page to hide the “In this Section” column.)

United States

Product                                           NDC Number                 Lot                      Expiration Date

MitoXANTRONE Injection, USP,        61703-343-18             Z054636AA          December 2014

(concentrate) 20 mg/10 mL,                                                        A014636AA          April 2015

2 mg/mL in 10 mL, 10 mL Vial,                                                  A024636AB          July 2015

Multi Dose Vial

MitoXANTRONE Injection, USP,        61703-343-65              A014643AA          April 2015

(concentrate) 25 mg/12.5 mL,

2 mg/mL in 12.5 mL, 12.5 mL Vial,

Multi Dose Vial

MitoXANTRONE Injection, USP,         61703-343-66             A014645AA          November 2015

(concentrate) 30 mg/15 mL,

2 mg/mL in 15 mL, 15 mL Vial,

Multi Dose Vial

Australia and New Zealand

Product                                            Product Code               Batch Number     Expiration Date

DBL™ MitoXANTRONE                        M4636A                        A024636AA           July 2015

Hydrochloride Injection

(concentrate) 20mg/10mL

Injection Vial

United Kingdom, Ireland, Cyprus, Saudi Arabia, Qatar, Oman and Bahrain

Product                                             List Number                Lot                      Expiration Date

MitoXANTRONE 2 mg/mL;                M4636AGB1                 A014636AB         April 2015

Concentrate for Infusion                                                              A024636AD         July 2015

Z054636AB         Dec 2014

Canada

Product                                 List Number       DIN               Lot                      Expiration Date

MitoXANTRONE for

Injection 20mg /10mL USP    4636A001           02244614      A024636AC         July 2015

Anyone with an existing inventory of the recalled lots should stop use and distribution, and quarantine the product immediately. This recall is being carried out to the user level (both human and veterinary).

Hospira has notified its direct customers via a recall letter and is arranging for impacted product to be returned to Stericycle in the US. For additional assistance in the US, call Stericycle at 1-844-265-7407 between the hours of 8 am and 5 pm ET, Monday through Friday. Customers outside the US should work with their local Hospira offices to return the product per local recall notifications.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or medcom@hospira.com (Available 24 hours a day/7 days per week).

To report adverse events or for product complaints, contact Hospira Global Complaint Management at 1-800-441-4100 (M-F, 8 am to 5 pm CT).

Adverse events or quality problems associated with Mitoxantrone can also be reported to the FDA’s MedWatch Adverse Event Reporting Program.

Vials of drug

Credit: Bill Branson

Hospira, Inc. has initiated a worldwide, user-level recall of 10 lots of Mitoxantrone (both human and veterinary) due to confirmed subpotency and elevated impurity levels.

Drugs in the affected lots may exhibit decreased effectiveness, require additional dosing, or prompt cumulative impurity toxicity requiring medical intervention.

However, Hospira has not received reports of any adverse events associated with subpotency and impurities for these lots to date.

The lots were distributed to hospitals and veterinary clinics worldwide from February 2013 through November 2014.

The following lots are affected by the recall. (To ensure this list displays properly, click the “Hide” icon on the right side of this page to hide the “In this Section” column.)

United States

Product                                           NDC Number                 Lot                      Expiration Date

MitoXANTRONE Injection, USP,        61703-343-18             Z054636AA          December 2014

(concentrate) 20 mg/10 mL,                                                        A014636AA          April 2015

2 mg/mL in 10 mL, 10 mL Vial,                                                  A024636AB          July 2015

Multi Dose Vial

MitoXANTRONE Injection, USP,        61703-343-65              A014643AA          April 2015

(concentrate) 25 mg/12.5 mL,

2 mg/mL in 12.5 mL, 12.5 mL Vial,

Multi Dose Vial

MitoXANTRONE Injection, USP,         61703-343-66             A014645AA          November 2015

(concentrate) 30 mg/15 mL,

2 mg/mL in 15 mL, 15 mL Vial,

Multi Dose Vial

Australia and New Zealand

Product                                            Product Code               Batch Number     Expiration Date

DBL™ MitoXANTRONE                        M4636A                        A024636AA           July 2015

Hydrochloride Injection

(concentrate) 20mg/10mL

Injection Vial

United Kingdom, Ireland, Cyprus, Saudi Arabia, Qatar, Oman and Bahrain

Product                                             List Number                Lot                      Expiration Date

MitoXANTRONE 2 mg/mL;                M4636AGB1                 A014636AB         April 2015

Concentrate for Infusion                                                              A024636AD         July 2015

Z054636AB         Dec 2014

Canada

Product                                 List Number       DIN               Lot                      Expiration Date

MitoXANTRONE for

Injection 20mg /10mL USP    4636A001           02244614      A024636AC         July 2015

Anyone with an existing inventory of the recalled lots should stop use and distribution, and quarantine the product immediately. This recall is being carried out to the user level (both human and veterinary).

Hospira has notified its direct customers via a recall letter and is arranging for impacted product to be returned to Stericycle in the US. For additional assistance in the US, call Stericycle at 1-844-265-7407 between the hours of 8 am and 5 pm ET, Monday through Friday. Customers outside the US should work with their local Hospira offices to return the product per local recall notifications.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or medcom@hospira.com (Available 24 hours a day/7 days per week).

To report adverse events or for product complaints, contact Hospira Global Complaint Management at 1-800-441-4100 (M-F, 8 am to 5 pm CT).

Adverse events or quality problems associated with Mitoxantrone can also be reported to the FDA’s MedWatch Adverse Event Reporting Program.

Vials of drug

Credit: Bill Branson

Hospira, Inc. has initiated a worldwide, user-level recall of 10 lots of Mitoxantrone (both human and veterinary) due to confirmed subpotency and elevated impurity levels.

Drugs in the affected lots may exhibit decreased effectiveness, require additional dosing, or prompt cumulative impurity toxicity requiring medical intervention.

However, Hospira has not received reports of any adverse events associated with subpotency and impurities for these lots to date.

The lots were distributed to hospitals and veterinary clinics worldwide from February 2013 through November 2014.

The following lots are affected by the recall. (To ensure this list displays properly, click the “Hide” icon on the right side of this page to hide the “In this Section” column.)

United States

Product                                           NDC Number                 Lot                      Expiration Date

MitoXANTRONE Injection, USP,        61703-343-18             Z054636AA          December 2014

(concentrate) 20 mg/10 mL,                                                        A014636AA          April 2015

2 mg/mL in 10 mL, 10 mL Vial,                                                  A024636AB          July 2015

Multi Dose Vial

MitoXANTRONE Injection, USP,        61703-343-65              A014643AA          April 2015

(concentrate) 25 mg/12.5 mL,

2 mg/mL in 12.5 mL, 12.5 mL Vial,

Multi Dose Vial

MitoXANTRONE Injection, USP,         61703-343-66             A014645AA          November 2015

(concentrate) 30 mg/15 mL,

2 mg/mL in 15 mL, 15 mL Vial,

Multi Dose Vial

Australia and New Zealand

Product                                            Product Code               Batch Number     Expiration Date

DBL™ MitoXANTRONE                        M4636A                        A024636AA           July 2015

Hydrochloride Injection

(concentrate) 20mg/10mL

Injection Vial

United Kingdom, Ireland, Cyprus, Saudi Arabia, Qatar, Oman and Bahrain

Product                                             List Number                Lot                      Expiration Date

MitoXANTRONE 2 mg/mL;                M4636AGB1                 A014636AB         April 2015

Concentrate for Infusion                                                              A024636AD         July 2015

Z054636AB         Dec 2014

Canada

Product                                 List Number       DIN               Lot                      Expiration Date

MitoXANTRONE for

Injection 20mg /10mL USP    4636A001           02244614      A024636AC         July 2015

Anyone with an existing inventory of the recalled lots should stop use and distribution, and quarantine the product immediately. This recall is being carried out to the user level (both human and veterinary).

Hospira has notified its direct customers via a recall letter and is arranging for impacted product to be returned to Stericycle in the US. For additional assistance in the US, call Stericycle at 1-844-265-7407 between the hours of 8 am and 5 pm ET, Monday through Friday. Customers outside the US should work with their local Hospira offices to return the product per local recall notifications.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 or medcom@hospira.com (Available 24 hours a day/7 days per week).

To report adverse events or for product complaints, contact Hospira Global Complaint Management at 1-800-441-4100 (M-F, 8 am to 5 pm CT).

Adverse events or quality problems associated with Mitoxantrone can also be reported to the FDA’s MedWatch Adverse Event Reporting Program.

Vials of a drug

The US Food and Drug Administration (FDA) has approved the intravenous administration of asparaginase Erwinia chrysanthemi (Erwinaze).

The product is indicated as a component of a multi-agent chemotherapy regimen to treat patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E coli-derived asparaginase.

Previously, the only FDA-approved route of administration for asparaginase Erwinia chrysanthemi was through intramuscular injection.

The FDA’s decision to expand the drug’s use was based on a pharmacokinetic study (published in Blood in 2013) of intravenous asparaginase Erwinia chrysanthemi.

The trial included 30 patients with ALL or lymphoblastic lymphoma who developed hypersensitivity (grade ≥ 2) to E coli–derived asparaginase. The patients’ median age was 6.5 years (range, 1-17), 63% were male, and 83% were Caucasian.

Patients received intravenous asparaginase Erwinia chrysanthemi at 25,000 IU/m²/dose, on a Monday/Wednesday/Friday schedule for 2 consecutive weeks (6 doses=1 cycle) for each dose of pegaspargase remaining in their original treatment plan. All other chemotherapy was continued per the original treatment plan.

Before the first dose of intravenous asparaginase Erwinia chrysanthemi, nadir serum asparaginase activity (NSAA) levels were below the limit of quantification (defined as 0.0129 IU/mL) for 91% of patients.

The study’s primary endpoint was the proportion of patients who achieved NSAA ≥ 0.1 IU/mL, which has been associated with complete asparagine depletion, at 48 hours after dose 5 in cycle 1. Nineteen of the 23 evaluable patients (83%) achieved this endpoint.

A secondary objective of the study was to determine the proportion of patients who achieved NSAA ≥ 0.1 IU/mL at 72 hours after dose 6 in cycle 1. Nine patients (45%) achieved this endpoint.

In all 30 patients, the most common asparaginase-related toxicities reported during cycle 1 were hypersensitivity (23%), vomiting (20%), nausea (20%), and hyperglycemia (13%). Pancreatitis and thrombosis each occurred in 3% of patients. One patient experienced a transient ischemic attack.

The most common grade 3 or 4 adverse event was febrile neutropenia (7%). Four patients discontinued treatment before completing cycle 1—3 of them due to hypersensitivity and 1 due to pancreatitis. There were no deaths.

This study was funded by Jazz Pharmaceuticals, the company developing asparaginase Erwinia chrysanthemi.

Vials of a drug

The US Food and Drug Administration (FDA) has approved the intravenous administration of asparaginase Erwinia chrysanthemi (Erwinaze).

The product is indicated as a component of a multi-agent chemotherapy regimen to treat patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E coli-derived asparaginase.

Previously, the only FDA-approved route of administration for asparaginase Erwinia chrysanthemi was through intramuscular injection.

The FDA’s decision to expand the drug’s use was based on a pharmacokinetic study (published in Blood in 2013) of intravenous asparaginase Erwinia chrysanthemi.

The trial included 30 patients with ALL or lymphoblastic lymphoma who developed hypersensitivity (grade ≥ 2) to E coli–derived asparaginase. The patients’ median age was 6.5 years (range, 1-17), 63% were male, and 83% were Caucasian.

Patients received intravenous asparaginase Erwinia chrysanthemi at 25,000 IU/m²/dose, on a Monday/Wednesday/Friday schedule for 2 consecutive weeks (6 doses=1 cycle) for each dose of pegaspargase remaining in their original treatment plan. All other chemotherapy was continued per the original treatment plan.

Before the first dose of intravenous asparaginase Erwinia chrysanthemi, nadir serum asparaginase activity (NSAA) levels were below the limit of quantification (defined as 0.0129 IU/mL) for 91% of patients.

The study’s primary endpoint was the proportion of patients who achieved NSAA ≥ 0.1 IU/mL, which has been associated with complete asparagine depletion, at 48 hours after dose 5 in cycle 1. Nineteen of the 23 evaluable patients (83%) achieved this endpoint.

A secondary objective of the study was to determine the proportion of patients who achieved NSAA ≥ 0.1 IU/mL at 72 hours after dose 6 in cycle 1. Nine patients (45%) achieved this endpoint.

In all 30 patients, the most common asparaginase-related toxicities reported during cycle 1 were hypersensitivity (23%), vomiting (20%), nausea (20%), and hyperglycemia (13%). Pancreatitis and thrombosis each occurred in 3% of patients. One patient experienced a transient ischemic attack.

The most common grade 3 or 4 adverse event was febrile neutropenia (7%). Four patients discontinued treatment before completing cycle 1—3 of them due to hypersensitivity and 1 due to pancreatitis. There were no deaths.

This study was funded by Jazz Pharmaceuticals, the company developing asparaginase Erwinia chrysanthemi.

Vials of a drug

The US Food and Drug Administration (FDA) has approved the intravenous administration of asparaginase Erwinia chrysanthemi (Erwinaze).

The product is indicated as a component of a multi-agent chemotherapy regimen to treat patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E coli-derived asparaginase.

Previously, the only FDA-approved route of administration for asparaginase Erwinia chrysanthemi was through intramuscular injection.

The FDA’s decision to expand the drug’s use was based on a pharmacokinetic study (published in Blood in 2013) of intravenous asparaginase Erwinia chrysanthemi.

The trial included 30 patients with ALL or lymphoblastic lymphoma who developed hypersensitivity (grade ≥ 2) to E coli–derived asparaginase. The patients’ median age was 6.5 years (range, 1-17), 63% were male, and 83% were Caucasian.

Patients received intravenous asparaginase Erwinia chrysanthemi at 25,000 IU/m²/dose, on a Monday/Wednesday/Friday schedule for 2 consecutive weeks (6 doses=1 cycle) for each dose of pegaspargase remaining in their original treatment plan. All other chemotherapy was continued per the original treatment plan.

Before the first dose of intravenous asparaginase Erwinia chrysanthemi, nadir serum asparaginase activity (NSAA) levels were below the limit of quantification (defined as 0.0129 IU/mL) for 91% of patients.

The study’s primary endpoint was the proportion of patients who achieved NSAA ≥ 0.1 IU/mL, which has been associated with complete asparagine depletion, at 48 hours after dose 5 in cycle 1. Nineteen of the 23 evaluable patients (83%) achieved this endpoint.

A secondary objective of the study was to determine the proportion of patients who achieved NSAA ≥ 0.1 IU/mL at 72 hours after dose 6 in cycle 1. Nine patients (45%) achieved this endpoint.

In all 30 patients, the most common asparaginase-related toxicities reported during cycle 1 were hypersensitivity (23%), vomiting (20%), nausea (20%), and hyperglycemia (13%). Pancreatitis and thrombosis each occurred in 3% of patients. One patient experienced a transient ischemic attack.

The most common grade 3 or 4 adverse event was febrile neutropenia (7%). Four patients discontinued treatment before completing cycle 1—3 of them due to hypersensitivity and 1 due to pancreatitis. There were no deaths.

This study was funded by Jazz Pharmaceuticals, the company developing asparaginase Erwinia chrysanthemi.