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Drug granted orphan designation for MM
The US Food and Drug Administration (FDA) has granted orphan designation for the drug CB-5083 to treat multiple myeloma (MM).
CB-5083 works by inhibiting p97, an enzyme that controls various aspects of protein homeostasis.
Inhibiting p97 function in cancers has been shown to generate irresolvable endoplasmic reticulum stress that induces a lethal unfolded protein response, which leads to apoptosis and antitumor activity.
CB-5083 has exhibited anticancer activity in preclinical research, and the drug is currently under investigation in two phase 1 studies—one in MM and one in solid tumor malignancies.
Research in MM
Preclinical research presented at ASH 2014 showed that CB-5083 inhibits MM cell viability in vitro. The drug also inhibited tumor growth in xenograft models of MM and in an orthometastatic model of MM.
In addition, CB-5083 demonstrated synergy with carfilzomib, bortezomib, and combination lenalidomide-dexamethasone.
CB-5083 is now under investigation in a phase 1 dose-escalation/dose-expansion trial of MM patients.
Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the drug in patients who have relapsed/refractory or refractory MM after receiving 2 or more lines of therapy, including an immunomodulatory agent and a proteasome inhibitor.
The goal is to enroll up to 60 patients in this trial at multiple US cancer centers that are part of the Multiple Myeloma Research Consortium. More information about the trial is available at www.clinicaltrials.gov (NCT02223598).
About orphan designation
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US. Orphan designation provides the sponsor of a drug with various development incentives.
The orphan designation for CB-5083 provides Cleave Biosciences with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits. 
The US Food and Drug Administration (FDA) has granted orphan designation for the drug CB-5083 to treat multiple myeloma (MM).
CB-5083 works by inhibiting p97, an enzyme that controls various aspects of protein homeostasis.
Inhibiting p97 function in cancers has been shown to generate irresolvable endoplasmic reticulum stress that induces a lethal unfolded protein response, which leads to apoptosis and antitumor activity.
CB-5083 has exhibited anticancer activity in preclinical research, and the drug is currently under investigation in two phase 1 studies—one in MM and one in solid tumor malignancies.
Research in MM
Preclinical research presented at ASH 2014 showed that CB-5083 inhibits MM cell viability in vitro. The drug also inhibited tumor growth in xenograft models of MM and in an orthometastatic model of MM.
In addition, CB-5083 demonstrated synergy with carfilzomib, bortezomib, and combination lenalidomide-dexamethasone.
CB-5083 is now under investigation in a phase 1 dose-escalation/dose-expansion trial of MM patients.
Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the drug in patients who have relapsed/refractory or refractory MM after receiving 2 or more lines of therapy, including an immunomodulatory agent and a proteasome inhibitor.
The goal is to enroll up to 60 patients in this trial at multiple US cancer centers that are part of the Multiple Myeloma Research Consortium. More information about the trial is available at www.clinicaltrials.gov (NCT02223598).
About orphan designation
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US. Orphan designation provides the sponsor of a drug with various development incentives.
The orphan designation for CB-5083 provides Cleave Biosciences with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.
The US Food and Drug Administration (FDA) has granted orphan designation for the drug CB-5083 to treat multiple myeloma (MM).
CB-5083 works by inhibiting p97, an enzyme that controls various aspects of protein homeostasis.
Inhibiting p97 function in cancers has been shown to generate irresolvable endoplasmic reticulum stress that induces a lethal unfolded protein response, which leads to apoptosis and antitumor activity.
CB-5083 has exhibited anticancer activity in preclinical research, and the drug is currently under investigation in two phase 1 studies—one in MM and one in solid tumor malignancies.
Research in MM
Preclinical research presented at ASH 2014 showed that CB-5083 inhibits MM cell viability in vitro. The drug also inhibited tumor growth in xenograft models of MM and in an orthometastatic model of MM.
In addition, CB-5083 demonstrated synergy with carfilzomib, bortezomib, and combination lenalidomide-dexamethasone.
CB-5083 is now under investigation in a phase 1 dose-escalation/dose-expansion trial of MM patients.
Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the drug in patients who have relapsed/refractory or refractory MM after receiving 2 or more lines of therapy, including an immunomodulatory agent and a proteasome inhibitor.
The goal is to enroll up to 60 patients in this trial at multiple US cancer centers that are part of the Multiple Myeloma Research Consortium. More information about the trial is available at www.clinicaltrials.gov (NCT02223598).
About orphan designation
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US. Orphan designation provides the sponsor of a drug with various development incentives.
The orphan designation for CB-5083 provides Cleave Biosciences with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.
NICE recommends edoxaban for VTE
Image by Keven MacKenzie
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for treating and preventing the recurrence of venous thromboembolism (VTE).
A committee advising NICE concluded that edoxaban is clinically effective, and the drug will be a cost-effective use of National Health Service resources.
“The newer oral anticoagulants like edoxaban tosylate are an alternative to warfarin as the mainstay of treatment to prevent recurrent blood clots,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The committee concluded that patients value newer oral anticoagulants such as edoxaban tosylate, which cause less disruption to their day-to-day lives than warfarin. We are pleased, therefore, to be able to recommend edoxaban tosylate as a further cost-effective option for treating [VTE] and preventing further episodes in adults.”
Clinical effectiveness
Edoxaban was recently approved in the European Union to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE). This approval was based on results of the Hokusai-VTE trial. The committee advising NICE analyzed data from this trial when considering the clinical effectiveness of edoxaban.
For Hokusai-VTE, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
Cost-effectiveness
The recommended dose of edoxaban is 60 mg once daily, or 30 mg once daily in specific patient groups—those with renal impairment, low body weight (60 kg or less), or concomitant use of potent permeability glycoprotein inhibitors—following treatment with a parenteral anticoagulant for at least 5 days.
Edoxaban costs £2.10 per 15 mg, 30 mg, or 60 mg tablet (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
Taking into account the lack of any clear evidence that edoxaban is significantly different from the other new oral anticoagulants, as well as the testimony of experts, the committee advising NICE concluded that the most plausible incremental cost-effectiveness ratio for edoxaban was likely to be in line with the other oral anticoagulants already recommended by NICE.
The draft guidance for edoxaban is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Image by Keven MacKenzie
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for treating and preventing the recurrence of venous thromboembolism (VTE).
A committee advising NICE concluded that edoxaban is clinically effective, and the drug will be a cost-effective use of National Health Service resources.
“The newer oral anticoagulants like edoxaban tosylate are an alternative to warfarin as the mainstay of treatment to prevent recurrent blood clots,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The committee concluded that patients value newer oral anticoagulants such as edoxaban tosylate, which cause less disruption to their day-to-day lives than warfarin. We are pleased, therefore, to be able to recommend edoxaban tosylate as a further cost-effective option for treating [VTE] and preventing further episodes in adults.”
Clinical effectiveness
Edoxaban was recently approved in the European Union to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE). This approval was based on results of the Hokusai-VTE trial. The committee advising NICE analyzed data from this trial when considering the clinical effectiveness of edoxaban.
For Hokusai-VTE, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
Cost-effectiveness
The recommended dose of edoxaban is 60 mg once daily, or 30 mg once daily in specific patient groups—those with renal impairment, low body weight (60 kg or less), or concomitant use of potent permeability glycoprotein inhibitors—following treatment with a parenteral anticoagulant for at least 5 days.
Edoxaban costs £2.10 per 15 mg, 30 mg, or 60 mg tablet (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
Taking into account the lack of any clear evidence that edoxaban is significantly different from the other new oral anticoagulants, as well as the testimony of experts, the committee advising NICE concluded that the most plausible incremental cost-effectiveness ratio for edoxaban was likely to be in line with the other oral anticoagulants already recommended by NICE.
The draft guidance for edoxaban is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Image by Keven MacKenzie
The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for treating and preventing the recurrence of venous thromboembolism (VTE).
A committee advising NICE concluded that edoxaban is clinically effective, and the drug will be a cost-effective use of National Health Service resources.
“The newer oral anticoagulants like edoxaban tosylate are an alternative to warfarin as the mainstay of treatment to prevent recurrent blood clots,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The committee concluded that patients value newer oral anticoagulants such as edoxaban tosylate, which cause less disruption to their day-to-day lives than warfarin. We are pleased, therefore, to be able to recommend edoxaban tosylate as a further cost-effective option for treating [VTE] and preventing further episodes in adults.”
Clinical effectiveness
Edoxaban was recently approved in the European Union to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE). This approval was based on results of the Hokusai-VTE trial. The committee advising NICE analyzed data from this trial when considering the clinical effectiveness of edoxaban.
For Hokusai-VTE, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
Cost-effectiveness
The recommended dose of edoxaban is 60 mg once daily, or 30 mg once daily in specific patient groups—those with renal impairment, low body weight (60 kg or less), or concomitant use of potent permeability glycoprotein inhibitors—following treatment with a parenteral anticoagulant for at least 5 days.
Edoxaban costs £2.10 per 15 mg, 30 mg, or 60 mg tablet (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
Taking into account the lack of any clear evidence that edoxaban is significantly different from the other new oral anticoagulants, as well as the testimony of experts, the committee advising NICE concluded that the most plausible incremental cost-effectiveness ratio for edoxaban was likely to be in line with the other oral anticoagulants already recommended by NICE.
The draft guidance for edoxaban is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Ibrutinib approved to treat WM in EU
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
The European Commission has granted marketing authorization for ibrutinib (Imbruvica) to treat Waldenstrom’s macroglobulinemia (WM).
The Bruton’s tyrosine kinase inhibitor is now approved to treat adults with WM who have received at least one prior therapy or as first-line treatment for patients considered unsuitable for chemo-immunotherapy.
Ibrutinib is the first therapy approved specifically for WM in the European Union (EU). The approval applies to all 28 EU member states, plus Iceland, Norway, and Liechtenstein.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the EU, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The European Commission’s approval of ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug (given at 420 mg once daily) in 63 patients with previously treated WM.
Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
EC approves edoxaban for patients with VTE, NVAF
Image by Andre E.X. Brown
The European Commission (EC) has approved edoxaban (Lixiana), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).
The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).
It can also be used to prevent stroke and systemic embolism in adults with NVAF who have one or more risk factors for stroke or systemic embolism, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, or transient ischemic attack.
The EC’s decision affects all 28 European Union member states, plus Iceland, Norway, and Liechtenstein. Edoxaban is already approved for use in the US, Japan, and Switzerland.
The EC based its approval of edoxaban on results of 2 phase 3 clinical trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.
Hokusai-VTE
In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
ENGAGE-AF TIMI 48
In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism 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 systemic embolism 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).
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.
Image by Andre E.X. Brown
The European Commission (EC) has approved edoxaban (Lixiana), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).
The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).
It can also be used to prevent stroke and systemic embolism in adults with NVAF who have one or more risk factors for stroke or systemic embolism, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, or transient ischemic attack.
The EC’s decision affects all 28 European Union member states, plus Iceland, Norway, and Liechtenstein. Edoxaban is already approved for use in the US, Japan, and Switzerland.
The EC based its approval of edoxaban on results of 2 phase 3 clinical trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.
Hokusai-VTE
In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
ENGAGE-AF TIMI 48
In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism 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 systemic embolism 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).
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.
Image by Andre E.X. Brown
The European Commission (EC) has approved edoxaban (Lixiana), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).
The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).
It can also be used to prevent stroke and systemic embolism in adults with NVAF who have one or more risk factors for stroke or systemic embolism, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, or transient ischemic attack.
The EC’s decision affects all 28 European Union member states, plus Iceland, Norway, and Liechtenstein. Edoxaban is already approved for use in the US, Japan, and Switzerland.
The EC based its approval of edoxaban on results of 2 phase 3 clinical trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.
Hokusai-VTE
In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. 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).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
ENGAGE-AF TIMI 48
In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism 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 systemic embolism 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).
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.
CHMP recommends panobinostat for MM
Photo courtesy of the CDC
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending regulatory approval for panobinostat (Farydak) to treat relapsed and/or refractory multiple myeloma (MM).
The drug is indicated for use in combination with bortezomib and dexamethasone to treat adults with MM who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent (IMiD).
Panobinostat is already approved for this indication in the US and Chile.
If the European Commission follows the CHMP’s recommendation, panobinostat will be the first histone deacetylase (HDAC) inhibitor approved to treat MM in the European Union.
The European Commission generally follows CHMP recommendations and delivers its final decision within 3 months of the recommendation. The decision will be applicable to all 28 European Union member states, plus Iceland, Norway, and Liechtenstein.
“Panobinostat is the first and only HDAC inhibitor recommended by the CHMP for the treatment of patients living with multiple myeloma who have progressed after standard-of-care therapy with bortezomib and an IMiD,” said Alessandro Riva, MD, Global Head of Oncology Development and Medical Affairs at Novartis Oncology, the company developing panobinostat.
“We are pleased with the positive CHMP opinion on panobinostat for previously treated patients because it brings us one step closer to providing a new treatment option for patients in need in Europe.”
The CHMP’s recommendation is based on efficacy and safety data in a subgroup analysis of 147 patients on the phase 3 PANORAMA-1 trial. Results from this analysis were recently presented at the 2015 ASCO Annual Meeting.
PANORAMA-1 was designed to compare panobinostat in combination with bortezomib and dexamethasone to bortezomib and dexamethasone alone in patients who had relapsed or relapsed and refractory MM.
At ASCO, researchers presented results in 147 patients who had received 2 or more prior treatment regimens, including bortezomib and an IMiD.
The patients who received panobinostat, bortezomib, and dexamethasone had a longer median progression-free survival than patients who received bortezomib and dexamethasone alone—12.5 months and 4.7 months, respectively (hazard ratio=0.47).
Common grade 3/4 adverse events in both treatment arms were thrombocytopenia, lymphopenia, neutropenia, diarrhea, asthenia/fatigue, and peripheral neuropathy. About 7% of patients in both arms died while on treatment.
Photo courtesy of the CDC
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending regulatory approval for panobinostat (Farydak) to treat relapsed and/or refractory multiple myeloma (MM).
The drug is indicated for use in combination with bortezomib and dexamethasone to treat adults with MM who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent (IMiD).
Panobinostat is already approved for this indication in the US and Chile.
If the European Commission follows the CHMP’s recommendation, panobinostat will be the first histone deacetylase (HDAC) inhibitor approved to treat MM in the European Union.
The European Commission generally follows CHMP recommendations and delivers its final decision within 3 months of the recommendation. The decision will be applicable to all 28 European Union member states, plus Iceland, Norway, and Liechtenstein.
“Panobinostat is the first and only HDAC inhibitor recommended by the CHMP for the treatment of patients living with multiple myeloma who have progressed after standard-of-care therapy with bortezomib and an IMiD,” said Alessandro Riva, MD, Global Head of Oncology Development and Medical Affairs at Novartis Oncology, the company developing panobinostat.
“We are pleased with the positive CHMP opinion on panobinostat for previously treated patients because it brings us one step closer to providing a new treatment option for patients in need in Europe.”
The CHMP’s recommendation is based on efficacy and safety data in a subgroup analysis of 147 patients on the phase 3 PANORAMA-1 trial. Results from this analysis were recently presented at the 2015 ASCO Annual Meeting.
PANORAMA-1 was designed to compare panobinostat in combination with bortezomib and dexamethasone to bortezomib and dexamethasone alone in patients who had relapsed or relapsed and refractory MM.
At ASCO, researchers presented results in 147 patients who had received 2 or more prior treatment regimens, including bortezomib and an IMiD.
The patients who received panobinostat, bortezomib, and dexamethasone had a longer median progression-free survival than patients who received bortezomib and dexamethasone alone—12.5 months and 4.7 months, respectively (hazard ratio=0.47).
Common grade 3/4 adverse events in both treatment arms were thrombocytopenia, lymphopenia, neutropenia, diarrhea, asthenia/fatigue, and peripheral neuropathy. About 7% of patients in both arms died while on treatment.
Photo courtesy of the CDC
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending regulatory approval for panobinostat (Farydak) to treat relapsed and/or refractory multiple myeloma (MM).
The drug is indicated for use in combination with bortezomib and dexamethasone to treat adults with MM who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent (IMiD).
Panobinostat is already approved for this indication in the US and Chile.
If the European Commission follows the CHMP’s recommendation, panobinostat will be the first histone deacetylase (HDAC) inhibitor approved to treat MM in the European Union.
The European Commission generally follows CHMP recommendations and delivers its final decision within 3 months of the recommendation. The decision will be applicable to all 28 European Union member states, plus Iceland, Norway, and Liechtenstein.
“Panobinostat is the first and only HDAC inhibitor recommended by the CHMP for the treatment of patients living with multiple myeloma who have progressed after standard-of-care therapy with bortezomib and an IMiD,” said Alessandro Riva, MD, Global Head of Oncology Development and Medical Affairs at Novartis Oncology, the company developing panobinostat.
“We are pleased with the positive CHMP opinion on panobinostat for previously treated patients because it brings us one step closer to providing a new treatment option for patients in need in Europe.”
The CHMP’s recommendation is based on efficacy and safety data in a subgroup analysis of 147 patients on the phase 3 PANORAMA-1 trial. Results from this analysis were recently presented at the 2015 ASCO Annual Meeting.
PANORAMA-1 was designed to compare panobinostat in combination with bortezomib and dexamethasone to bortezomib and dexamethasone alone in patients who had relapsed or relapsed and refractory MM.
At ASCO, researchers presented results in 147 patients who had received 2 or more prior treatment regimens, including bortezomib and an IMiD.
The patients who received panobinostat, bortezomib, and dexamethasone had a longer median progression-free survival than patients who received bortezomib and dexamethasone alone—12.5 months and 4.7 months, respectively (hazard ratio=0.47).
Common grade 3/4 adverse events in both treatment arms were thrombocytopenia, lymphopenia, neutropenia, diarrhea, asthenia/fatigue, and peripheral neuropathy. About 7% of patients in both arms died while on treatment.
FDA grants vaccine orphan designation for MM
The US Food and Drug Administration (FDA) has granted a novel vaccine orphan designation as a treatment for multiple myeloma (MM).
The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.
ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.
Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.
The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.
The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.
There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.
A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.
ImMucin is under development by Vaxil Biotherapeutics Ltd. The vaccine also has orphan designation as a treatment for MM in the European Union.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves ImMucin to treat patients with MM, orphan designation will provide Vaxil Biotherapeutics with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted a novel vaccine orphan designation as a treatment for multiple myeloma (MM).
The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.
ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.
Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.
The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.
The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.
There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.
A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.
ImMucin is under development by Vaxil Biotherapeutics Ltd. The vaccine also has orphan designation as a treatment for MM in the European Union.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves ImMucin to treat patients with MM, orphan designation will provide Vaxil Biotherapeutics with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted a novel vaccine orphan designation as a treatment for multiple myeloma (MM).
The vaccine, known as ImMucin, targets the signal peptide domain of the MUC1 tumor antigen.
ImMucin works by “teaching” the immune system to identify and destroy cells that display a short, specific, 21-mer portion from MUC1, which appears on 90% of all cancer cells but not in patients’ blood.
Results of a phase 1/2 trial suggested that ImMucin was safe and active in MM patients. The trial included 15 MUC1-positive patients who had residual or biochemically progressive disease after autologous stem cell transplant.
The patients received 6 or 12 bi-weekly intradermal doses of ImMucin co-administered with human granulocyte-macrophage colony-stimulating factor.
The researchers said the vaccine was well-tolerated, as all adverse events were temporary, grade 1-2 in nature, and resolved spontaneously.
There was a significant decrease in soluble MUC1 levels in 9 patients, and 11 patients had stable disease or clinical improvement that persisted for 17.5 months to more than 41.3 months.
A follow-on study (which is ongoing) in patients who responded to ImMucin has shown that some patients can go more than 4 years without requiring any further treatment for their disease.
ImMucin is under development by Vaxil Biotherapeutics Ltd. The vaccine also has orphan designation as a treatment for MM in the European Union.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves ImMucin to treat patients with MM, orphan designation will provide Vaxil Biotherapeutics with 7 years of marketing exclusivity in the US.
FDA approves antiplatelet drug for PCI patients
Photo courtesy of
The Medicines Company
The US Food and Drug Administration (FDA) has approved the intravenous antiplatelet agent cangrelor (Kengreal) for use in adults undergoing percutaneous coronary intervention (PCI).
The drug can now be used to reduce periprocedural thrombotic events in patients who have not been treated with a P2Y12 inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor.
The FDA’s approval of cangrelor was based on results of the CHAMPION PHOENIX trial.
In this phase 3 trial, researchers compared cangrelor to clopidogrel in 11,145 patients undergoing PCI.
The study’s primary efficacy endpoint was the incidence of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis.
At 48 hours, 4.7% of patients in the cangrelor arm had met this endpoint, compared to 5.9% of patients in the clopidogrel arm (P=0.005). At 30 days, the incidence was 6.0% in the cangrelor arm and 7.0% in the clopidogrel arm (P=0.03).
The study’s primary safety endpoint was severe bleeding according to GUSTO criteria. At 48 hours, major bleeding had occurred in 0.16% of patients in the cangrelor arm and 0.11% of patients in the clopidogrel arm (P=0.44).
Major bleeding occurred in 4.3% of patients on cangrelor and 2.5% of patients on clopidogrel (P<0.001). And minor bleeding occurred in 11.8% of patients on cangrelor and 8.6% of patients on clopidogrel (P<0.001).
Cangrelor is manufactured by The Medicines Company, which is based in Parsippany, New Jersey.
Photo courtesy of
The Medicines Company
The US Food and Drug Administration (FDA) has approved the intravenous antiplatelet agent cangrelor (Kengreal) for use in adults undergoing percutaneous coronary intervention (PCI).
The drug can now be used to reduce periprocedural thrombotic events in patients who have not been treated with a P2Y12 inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor.
The FDA’s approval of cangrelor was based on results of the CHAMPION PHOENIX trial.
In this phase 3 trial, researchers compared cangrelor to clopidogrel in 11,145 patients undergoing PCI.
The study’s primary efficacy endpoint was the incidence of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis.
At 48 hours, 4.7% of patients in the cangrelor arm had met this endpoint, compared to 5.9% of patients in the clopidogrel arm (P=0.005). At 30 days, the incidence was 6.0% in the cangrelor arm and 7.0% in the clopidogrel arm (P=0.03).
The study’s primary safety endpoint was severe bleeding according to GUSTO criteria. At 48 hours, major bleeding had occurred in 0.16% of patients in the cangrelor arm and 0.11% of patients in the clopidogrel arm (P=0.44).
Major bleeding occurred in 4.3% of patients on cangrelor and 2.5% of patients on clopidogrel (P<0.001). And minor bleeding occurred in 11.8% of patients on cangrelor and 8.6% of patients on clopidogrel (P<0.001).
Cangrelor is manufactured by The Medicines Company, which is based in Parsippany, New Jersey.
Photo courtesy of
The Medicines Company
The US Food and Drug Administration (FDA) has approved the intravenous antiplatelet agent cangrelor (Kengreal) for use in adults undergoing percutaneous coronary intervention (PCI).
The drug can now be used to reduce periprocedural thrombotic events in patients who have not been treated with a P2Y12 inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor.
The FDA’s approval of cangrelor was based on results of the CHAMPION PHOENIX trial.
In this phase 3 trial, researchers compared cangrelor to clopidogrel in 11,145 patients undergoing PCI.
The study’s primary efficacy endpoint was the incidence of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis.
At 48 hours, 4.7% of patients in the cangrelor arm had met this endpoint, compared to 5.9% of patients in the clopidogrel arm (P=0.005). At 30 days, the incidence was 6.0% in the cangrelor arm and 7.0% in the clopidogrel arm (P=0.03).
The study’s primary safety endpoint was severe bleeding according to GUSTO criteria. At 48 hours, major bleeding had occurred in 0.16% of patients in the cangrelor arm and 0.11% of patients in the clopidogrel arm (P=0.44).
Major bleeding occurred in 4.3% of patients on cangrelor and 2.5% of patients on clopidogrel (P<0.001). And minor bleeding occurred in 11.8% of patients on cangrelor and 8.6% of patients on clopidogrel (P<0.001).
Cangrelor is manufactured by The Medicines Company, which is based in Parsippany, New Jersey.
IDH1 inhibitor gets orphan designation for AML
The US Food and Drug Administration (FDA) has granted orphan designation for AG-120 to treat patients with acute myeloid leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.
AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.
The FDA granted AG-120 fast track designation last month.
“Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120.
“We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing phase 1 study of AG-120 at the Congress of the European Hematology Association later this week.”
Phase 1 trial
Results from the phase 1 study of AG-120 in patients with hematologic malignancies were previously presented at the EORTC-NCI-AACR symposium in November 2014.
The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments. The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.
Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.
Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.
Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.
Eight patients experienced serious adverse events, but these were primarily related to disease progression.
One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.
There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves AG-120 to treat patients with AML, orphan designation will provide Agios with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted orphan designation for AG-120 to treat patients with acute myeloid leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.
AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.
The FDA granted AG-120 fast track designation last month.
“Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120.
“We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing phase 1 study of AG-120 at the Congress of the European Hematology Association later this week.”
Phase 1 trial
Results from the phase 1 study of AG-120 in patients with hematologic malignancies were previously presented at the EORTC-NCI-AACR symposium in November 2014.
The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments. The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.
Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.
Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.
Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.
Eight patients experienced serious adverse events, but these were primarily related to disease progression.
One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.
There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves AG-120 to treat patients with AML, orphan designation will provide Agios with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted orphan designation for AG-120 to treat patients with acute myeloid leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.
AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.
The FDA granted AG-120 fast track designation last month.
“Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120.
“We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing phase 1 study of AG-120 at the Congress of the European Hematology Association later this week.”
Phase 1 trial
Results from the phase 1 study of AG-120 in patients with hematologic malignancies were previously presented at the EORTC-NCI-AACR symposium in November 2014.
The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments. The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.
Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.
Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.
Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.
Eight patients experienced serious adverse events, but these were primarily related to disease progression.
One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.
There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If the FDA approves AG-120 to treat patients with AML, orphan designation will provide Agios with 7 years of marketing exclusivity in the US.
Drug granted orphan status for hemophilia A
The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.
The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.
ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.
“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.
“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”
ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.
The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.
ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.
“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.
“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”
ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.
The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.
The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.
ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.
“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.
“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”
ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.
About orphan designation
The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.
Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.
If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.
Mylan recalls gemcitabine, methotrexate
Photo by Bill Branson
Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.
This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.
Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.
The recall includes the following products:
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015
Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016
Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016
Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016
Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.
Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.
Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.
Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or customer.service@mylan.com, Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.
Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
Photo by Bill Branson
Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.
This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.
Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.
The recall includes the following products:
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015
Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016
Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016
Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016
Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.
Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.
Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.
Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or customer.service@mylan.com, Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.
Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.
Photo by Bill Branson
Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.
This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.
Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.
The recall includes the following products:
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015
Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016
Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016
Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016
Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016
Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.
Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.
Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.
Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or customer.service@mylan.com, Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.
Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.