Pharmacy

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).

The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.

The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).

The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.

The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for rivaroxaban (XARELTO®).

The sNDA is for a 10 mg once-daily dose of rivaroxaban to reduce the risk of venous thromboembolism (VTE) in patients who have received at least 6 months of standard anticoagulant therapy.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the rivaroxaban sNDA by October 28, 2017.

The sNDA is supported by data from the EINSTEIN CHOICE study. Patients enrolled in this study had confirmed VTE and were treated initially with standard anticoagulant therapy for 6 to 12 months.

During EINSTEIN CHOICE, 3365 patients received rivaroxaban at 10 mg, rivaroxaban at 20 mg, or aspirin at 100 mg once daily for up to 12 months of extended treatment.

Both rivaroxaban doses were superior to aspirin in preventing fatal or non-fatal recurrent VTE, the study’s primary efficacy endpoint.

The rate of recurrent VTE was 1.2% in the 10 mg rivaroxaban arm (hazard ratio [HR]=0.26; 95% CI, 0.14 to 0.47; P<0.001), 1.5% in the 20 mg rivaroxaban arm (HR=0.34; 95% CI, 0.20 to 0.59; P<0.001), and 4.4% in the aspirin arm. Fatal VTE occurred in 0%, 0.2%, and 0.2% of patients, respectively.

The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.

The rate of major bleeding was 0.4% for the 10 mg rivaroxaban group (HR=1.64; 95% CI, 0.39 to 6.84; P=0.50), 0.5% for the 20 mg rivaroxaban group (HR=2.01; 95% CI, 0.50 to 8.04; P=0.32), and 0.3% for the aspirin group.

Photo courtesy of CDC

The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.

Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.

Betrixaban had also received fast track designation from the FDA.

Betrixaban is Portola’s first commercial product.

The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.

The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.

Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.

Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.

Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.

Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).

The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.

Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.

The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).

The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.

The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.

Portola expects to launch betrixaban between August and November 2017.

The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.

Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.

Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.

Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.

See the full prescribing information for more details on betrixaban. 

Photo courtesy of CDC

The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.

Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.

Betrixaban had also received fast track designation from the FDA.

Betrixaban is Portola’s first commercial product.

The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.

The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.

Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.

Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.

Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.

Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).

The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.

Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.

The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).

The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.

The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.

Portola expects to launch betrixaban between August and November 2017.

The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.

Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.

Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.

Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.

See the full prescribing information for more details on betrixaban. 

Photo courtesy of CDC

The oral, once-daily factor Xa inhibitor betrixaban (Bevyxxa®) was granted approval by the US Food and Drug Administration (FDA) under priority review.

Betrixaban is the first and only anticoagulant for hospital and extended duration prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness at risk for thromboembolic complications due to restricted mobility and other risk factors for VTE, according to Portola Pharmaceuticals, Inc, the drug’s developer.

Betrixaban had also received fast track designation from the FDA.

Betrixaban is Portola’s first commercial product.

The FDA approved betrixaban based on data from the phase 3 APEX trial, a randomized, double-blind multinational clinical trial comparing extended duration betrixaban to short duration of enoxaparin.

The trial enrolled 7513 patients at more than 450 clinical sites worldwide. The patients were acutely ill with medical conditions, hospitalized, and had risk factors for VTE.

Patients who received betrixaban had an initial dose of 160 mg orally on day 1, 80 mg once daily for 35 to 42 days, and a placebo injection once daily for 6 to 14 days.

Patients who received enoxaparin had a 40 mg injection subcutaneously once daily for 6 to 14 days and a placebo pill orally once daily for 35 to 42 days.

Efficacy data was analyzed in 7441 patients and assessed by a composite outcome score comprising either the occurrence of asymptomatic proximal deep vein thrombosis (DVT) or symptomatic DVT, non-fatal pulmonary embolism (PE), or VTE-related death.

Investigators observed fewer events in patients receiving betrixaban (4.4%) compared with those taking enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91) with no significant increase in major bleeding (0.67% vs 0.57%, respectively).

The most common adverse reactions with betrixaban occurring in 5% or more of patients were related to bleeding.

Overall, 54% of patients receiving betrixaban experienced at least one adverse reaction compared with 52% taking enoxaparin.

The frequency of patients reporting serious adverse reactions was similar between betrixaban (18%) and enoxaparin (17%).

The most frequent reason for treatment discontinuation was bleeding, with an incidence rate for all bleeding episodes of 2.4% and 1.2% for betrixaban and enoxaparin, respectively.

The incidence rate for major bleeding episodes was 0.67% and 0.57% for betrixaban and enoxaparin, respectively.

Portola expects to launch betrixaban between August and November 2017.

The European Medicines Agency’s Committee for Human Medicinal Products (CHMP) is reviewing betrixaban for marketing authorization under its standard review period.

Portola is also advancing clinical development of andexanet alfa (AndexXa®) and cerdulatinib.

Andexanet alfa is a recombinant protein designed to reverse the anticoagulant effect in patients treated with an oral or injectable factor Xa inhibitor.

Cerdulatinib is a Syk/JAK inhibitor to treat hematologic cancers.

See the full prescribing information for more details on betrixaban. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Syringe

The US Food and Drug Administration (FDA) approved a new, subcutaneous (SC) formulation of rituximab with hyaluronidase human (Rituxan Hycela™).

The new formulation includes the same monoclonal antibody as intravenous rituximab, but is combined with an enzyme that helps to deliver rituximab under the skin.

The new treatment reduces administration time from 1.5 hours or more for intravenous rituximab to 5 to 7 minutes for the subcutaneous injection.

It is approved for use in adults with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL).

“[P]eople with 3 of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” said Sandra Horning, MD, chief medical officer of Genentech.

Rituxan Hycela is manufactured by Genentech, Inc, a member of the Roche Group, and jointly marketed by Biogen and Genentech USA, Inc.

“People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important,” she noted.

The FDA based its decision on results from 4 clinical studies:

• SABRINA (NCT01200758): Phase 3 combination study with chemotherapy and maintenance study in previously untreated FL
• SAWYER (NCT01292603): Phase 1b study in previously untreated CLL
• MabEase (NCT01649856): Phase 3 study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase 3 patient preference study in previously untreated FL and DLBCL

This last study showed that 77% of patients preferred subcutaneous over intravenous administration, primarily because it reduced administration time.

Together, these trials represented nearly 2,000 people and demonstrated that subcutaneous administration of rituximab/hyaluronidase resulted in non-inferior levels of rituximab in the blood compared to intravenous rituximab.

And the subcutaneous formulation also demonstrated comparable clinical efficacy outcomes to the intravenous formulation.

Patients must have had at least 1 full dose of intravenous rituximab without severe adverse reactions before receiving the subcutaneous injection. There is a higher risk of certain severe adverse reactions during the first infusion.

The safety profile of rituximab/hyaluronidase is also comparable to intravenous rituximab, except for cutaneous reactions.

The most common (≥20%) adverse reactions observed with rituximab/hyaluronidase were:

• In FL, infections, neutropenia, nausea, constipation, cough, and fatigue.
• In DLBCL, infections, neutropenia, alopecia, nausea, and anemia.
• In CLL, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and erythema at the injection site.

Rituxan Hycela will be available in the US within 1 to 2 weeks, according to the manufacturer. Intravenous rituximab will continue to be available.

A subcutaneous formulation of rituximab (MabThera) had previously been approved for use in European markets by the European Commission.

For further information on the new US formulation, see the full prescribing information. 

Photo courtesy of FDA

The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for the use of fostamatinib disodium (Tavalisse™) in the treatment of patients with chronic/persistent immune thrombocytopenia (ITP).

Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor that investigators believe may address an underlying autoimmune cause of ITP by impeding platelet destruction.

Rigel Pharmaceuticals, the drug’s developer, anticipates an action date by the FDA of April 17, 2018.

The FDA previously granted fostamatinib orphan drug designation.

Data from 3 clinical studies support the new drug application. Study 047 and 048 were randomized placebo-controlled trials, and study 049 was an open-label extension study.

Together with an initial proof of concept study, the application included data on 163 ITP patients. Fostamatinib has been evaluated in over 4,600 individuals across all indications.

The patients enrolled in studies 047 and 048 had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Study 047

In this study, 51 patients were randomized to fostamatinib and 25 to placebo.

The median platelet counts at baseline were 15,000/uL and 16,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

The primary efficacy endpoint in both study 047 and 048 was a stable platelet response, defined as achieving platelet counts greater than 50,000/uL for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In study 047, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

Study 048

 Fifty patients were randomized to fostamatinib and 24 to placebo.

Patients’ median platelet counts at baseline were 16,000/uL and 21,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

In this study, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

However, when the data from study 047 and 048 were combined, the response rate was significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

"The FDA acceptance for filing of our NDA is an exciting milestone for Rigel," Raul Rodriguez, Rigel's president and chief executive officer, said.

The approval of fostamatinib “will provide a new treatment option for patients with chronic or persistent ITP,” he affirmed. “We look forward to working closely with the FDA as they review our submission." 

Photo courtesy of FDA

The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for the use of fostamatinib disodium (Tavalisse™) in the treatment of patients with chronic/persistent immune thrombocytopenia (ITP).

Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor that investigators believe may address an underlying autoimmune cause of ITP by impeding platelet destruction.

Rigel Pharmaceuticals, the drug’s developer, anticipates an action date by the FDA of April 17, 2018.

The FDA previously granted fostamatinib orphan drug designation.

Data from 3 clinical studies support the new drug application. Study 047 and 048 were randomized placebo-controlled trials, and study 049 was an open-label extension study.

Together with an initial proof of concept study, the application included data on 163 ITP patients. Fostamatinib has been evaluated in over 4,600 individuals across all indications.

The patients enrolled in studies 047 and 048 had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Study 047

In this study, 51 patients were randomized to fostamatinib and 25 to placebo.

The median platelet counts at baseline were 15,000/uL and 16,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

The primary efficacy endpoint in both study 047 and 048 was a stable platelet response, defined as achieving platelet counts greater than 50,000/uL for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In study 047, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

Study 048

 Fifty patients were randomized to fostamatinib and 24 to placebo.

Patients’ median platelet counts at baseline were 16,000/uL and 21,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

In this study, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

However, when the data from study 047 and 048 were combined, the response rate was significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

"The FDA acceptance for filing of our NDA is an exciting milestone for Rigel," Raul Rodriguez, Rigel's president and chief executive officer, said.

The approval of fostamatinib “will provide a new treatment option for patients with chronic or persistent ITP,” he affirmed. “We look forward to working closely with the FDA as they review our submission." 

Photo courtesy of FDA

The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for the use of fostamatinib disodium (Tavalisse™) in the treatment of patients with chronic/persistent immune thrombocytopenia (ITP).

Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor that investigators believe may address an underlying autoimmune cause of ITP by impeding platelet destruction.

Rigel Pharmaceuticals, the drug’s developer, anticipates an action date by the FDA of April 17, 2018.

The FDA previously granted fostamatinib orphan drug designation.

Data from 3 clinical studies support the new drug application. Study 047 and 048 were randomized placebo-controlled trials, and study 049 was an open-label extension study.

Together with an initial proof of concept study, the application included data on 163 ITP patients. Fostamatinib has been evaluated in over 4,600 individuals across all indications.

The patients enrolled in studies 047 and 048 had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL.

In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.

Study 047

In this study, 51 patients were randomized to fostamatinib and 25 to placebo.

The median platelet counts at baseline were 15,000/uL and 16,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.

The primary efficacy endpoint in both study 047 and 048 was a stable platelet response, defined as achieving platelet counts greater than 50,000/uL for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.

In study 047, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).

Study 048

 Fifty patients were randomized to fostamatinib and 24 to placebo.

Patients’ median platelet counts at baseline were 16,000/uL and 21,000/uL in the fostamatinib and placebo arms, respectively.

The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.

In this study, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).

However, when the data from study 047 and 048 were combined, the response rate was significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).

"The FDA acceptance for filing of our NDA is an exciting milestone for Rigel," Raul Rodriguez, Rigel's president and chief executive officer, said.

The approval of fostamatinib “will provide a new treatment option for patients with chronic or persistent ITP,” he affirmed. “We look forward to working closely with the FDA as they review our submission." 

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo by Linda Bartlett

The European Commission (EC) has approved the Sandoz biosimilar rituximab (Rixathon^®) for use in the European Economic Area.

Rixathon is approved for all indications of the reference medicine, MabThera®, including follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and immunologic diseases such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

This approval allows Rixathon to be marketed in the member states of the European Union and Iceland, Liechtenstein, and Norway, members of the European Free Trade Association.

The approval “represents a big win for patients in Europe with blood cancers or immunological diseases,” according to Carol Lynch, global head of Biopharmaceuticals at Sandoz.

“Rixathon will be one of the 5 major launches we plan in the next 4 years,” she said.

Earlier in the year, the European Medicines Agency’s Committee for Medicinal Products for Human Use had recommended marketing authorization for Rixathon.

The EC based its approval on a comprehensive development program generating analytical, preclinical, and clinical data.  Clinical studies included ASSIST-RA and ASSIST-FL.

ASSIST-RA demonstrated that the biosimilar product has equivalent pharmacokinetic and pharmacodynamic profiles to the reference medicine, with no clinically meaningful differences in safety, tolerability, or immunogenicity in patients with rheumatoid arthritis.

ASSIST-FL was a phase 3 study confirming efficacy and safety. The study met its primary endpoint of equivalence in overall response rate between the biosimilar product and the reference medicine after 6 months.

ASSIST-FL also confirmed the comparable safety profiles of the 2 medicines.

Sandoz is a division of the Swiss pharmaceutical company Novartis. MabThera is a registered trademark of F. Hoffmann-La-Roche AG.

Another Sandoz biosimilar rituximab has been approved in the EU as Riximyo® under a duplicate marketing authorization. 

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex®) in combination with pomalidomide (POM) and dexamethasone (dex) for the treatment of multiple myeloma (MM) in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI).

The FDA previously approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with MM who had at least 1 prior therapy.

Daratumumab is also approved by the FDA as monotherapy in MM patients who had at least 3 prior lines of therapy, including a PI and an immunomodulatory (IMiD) agent, or who are double refractory to a PI and an IMiD.

The latest indication is based on the results of the phase 1b MMY1001 EQUULEUS study, which demonstrated that daratumumab produced an overall response (OR) rate of 59% in combination with pomalidomide and dexamethasone, and a very good partial response (VGPR) in 28% of patients.

EQUULEUS study

The daratumumab-POM-Dex arm of the phase 1 open-label EQUULEUS study included 103 MM patients who had received prior treatment with a PI and an immunomodulatory agent.

Patients were a median age of 64 years, and 8% were older than 75.

They had received a median of 4 prior lines of therapy, and 74% had received prior autologous stem cell transplant.

Most (89%) were refractory to lenalidomide and 71% were refractory to bortezomib. Almost two thirds (64%) were refractory to bortezomib and lenalidomide.

Patients were treated with 16 mg/kg of daratumumab in combination with POM and Dex, and 6% achieved a complete response (CR) and 8% achieved a stringent CR.

The median time to response was 1 month (range, 0.9 to 2.8), and the median duration of response was 13.6 months (range, 0.9+ to 14.6+ months).

The most frequent adverse events (AEs) reported in more than 20% of patients were infusion reactions, fatigue, and upper respiratory tract infections (50% each), cough (43%), diarrhea (38%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), and vomiting (21%).

The overall incidence of serious adverse reactions was 49%.

Grade 3/4 serious AEs reported in 5% of patients or more included pneumonia (7%).

The most common treatment-emergent hematologic laboratory abnormalities included lymphopenia (94%), neutropenia (95%), thrombocytopenia (75%), and anemia (57%).

And the most common grade 3/4 treatment-emergent hematology laboratory abnormalities were neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

Daratumumab is being developed by Janssen Biotech, Inc., under an exclusive worldwide license to develop, manufacture, and commercialize daratumumab from Genmab.

See the package insert for full prescribing information. 

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Photo courtesy of Merck

Merck announced that it is pausing enrollment onto 2 phase 3 trials of pembrolizumab (Keytruda®) in combination with other agents to treat multiple myeloma (MM).

An external Data Monitoring Committee recommended the trial be interrupted “to allow for additional information be collected to better understand more reports of death” in the pembrolizumab groups in the KEYNOTE-183 and KEYNOTE-185 trials.

Patients currently enrolled on the trials can continue to receive treatment. Other pembrolizumab trials are continuing without changes.

Merck in its statement did not disclose the number of deaths nor provide any other details on the deaths.

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

The US Food & Drug Administration approved pembrolizumab to treat unresectable or metastatic melanoma after ipilimumab treatment.

Pembrolizumab has also been approved to treat non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability-high solid tumors.

KEYNOTE-183 (NCT02576977), which has an estimated enrollment of 300 patients, is comparing the combination of pembrolizumab, pomalidomide, and low-dose dexamethasone to pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory MM who have undergone at least 2 lines of prior therapy.

KEYNOTE-185 (NCT02579863), which has an estimated enrollment of 640 patients, is comparing the combination of pembrolizumab, lenalidomide, and low-dose dexamethasone to lenalidomide and low-dose desamethasone alone in patients with newly diagnosed and treatment-native MM who are ineligible for autologous stem cell transplant.

The comparator agents pomalidomide (Pomalyst®) and lenalidomide (Revlimid®) are products of Celgene Corporation. 

Antihemophilic factor

Nonacog beta pegol (N9-GP, Rebinyn®), a recombinant, GlycoPEGylated coagulation factor IX, has been approved by the US Food and Drug Administration (FDA) for on-demand treatment and control of bleeding episodes in adults and children with hemophilia B.

It is also indicated for the perioperative management of bleeding in these individuals. However, it is not indicated for routine prophylaxis or for immune tolerance induction.

NovoNordisk, the manufacturer of the drug, expects the launch of the coagulation factor in the United States to take place in the first half of 2018.

N9-GP earlier this year had been recommended for marketing authorization by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as Refixia.^® On June 6 it was actually granted marketing authorization, which covers all 28 European Union member states.

The FDA based its approval on the efficacy and safety evaluation of 115 previously treated patients across the four paradigm^TM clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Of 597 new bleeding episodes in 79 of 105 patients, 551 (93%) were resolved successfully with good or excellent ratings by the patients or study site investigator. Forty (7%) were rated as moderate or poor.

Most (87%) were resolved with 1 injection, 60 (10%) with 2 injections, and 16 (3%) with more than 2 injections.

The median dose to treat a bleeding episode was 42.3 IU/kg.

On-demand treatment had a success rate of 95%, with 120 (84%) of the 143 bleeds treated with one injection.

For perioperative management, N9-GP was rated as excellent or good for 13 surgeries, for a success rate of 100%.

Patients received a preoperative dose of 80 IU/kg. No patient required additional doses on the day of surgery.

During the postoperative period, patients required additional 40 IU/kg doses. The mean total consumption of factor in the pre- and postoperative period was 241 IU/kg (range, 8 – 460 IU/kg.

No unexpected postoperative bleeding occurred.

For full prescribing information, see the package insert. 

Antihemophilic factor

Nonacog beta pegol (N9-GP, Rebinyn®), a recombinant, GlycoPEGylated coagulation factor IX, has been approved by the US Food and Drug Administration (FDA) for on-demand treatment and control of bleeding episodes in adults and children with hemophilia B.

It is also indicated for the perioperative management of bleeding in these individuals. However, it is not indicated for routine prophylaxis or for immune tolerance induction.

NovoNordisk, the manufacturer of the drug, expects the launch of the coagulation factor in the United States to take place in the first half of 2018.

N9-GP earlier this year had been recommended for marketing authorization by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as Refixia.^® On June 6 it was actually granted marketing authorization, which covers all 28 European Union member states.

The FDA based its approval on the efficacy and safety evaluation of 115 previously treated patients across the four paradigm^TM clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Of 597 new bleeding episodes in 79 of 105 patients, 551 (93%) were resolved successfully with good or excellent ratings by the patients or study site investigator. Forty (7%) were rated as moderate or poor.

Most (87%) were resolved with 1 injection, 60 (10%) with 2 injections, and 16 (3%) with more than 2 injections.

The median dose to treat a bleeding episode was 42.3 IU/kg.

On-demand treatment had a success rate of 95%, with 120 (84%) of the 143 bleeds treated with one injection.

For perioperative management, N9-GP was rated as excellent or good for 13 surgeries, for a success rate of 100%.

Patients received a preoperative dose of 80 IU/kg. No patient required additional doses on the day of surgery.

During the postoperative period, patients required additional 40 IU/kg doses. The mean total consumption of factor in the pre- and postoperative period was 241 IU/kg (range, 8 – 460 IU/kg.

No unexpected postoperative bleeding occurred.

For full prescribing information, see the package insert. 

Antihemophilic factor

Nonacog beta pegol (N9-GP, Rebinyn®), a recombinant, GlycoPEGylated coagulation factor IX, has been approved by the US Food and Drug Administration (FDA) for on-demand treatment and control of bleeding episodes in adults and children with hemophilia B.

It is also indicated for the perioperative management of bleeding in these individuals. However, it is not indicated for routine prophylaxis or for immune tolerance induction.

NovoNordisk, the manufacturer of the drug, expects the launch of the coagulation factor in the United States to take place in the first half of 2018.

N9-GP earlier this year had been recommended for marketing authorization by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as Refixia.^® On June 6 it was actually granted marketing authorization, which covers all 28 European Union member states.

The FDA based its approval on the efficacy and safety evaluation of 115 previously treated patients across the four paradigm^TM clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Of 597 new bleeding episodes in 79 of 105 patients, 551 (93%) were resolved successfully with good or excellent ratings by the patients or study site investigator. Forty (7%) were rated as moderate or poor.

Most (87%) were resolved with 1 injection, 60 (10%) with 2 injections, and 16 (3%) with more than 2 injections.

The median dose to treat a bleeding episode was 42.3 IU/kg.

On-demand treatment had a success rate of 95%, with 120 (84%) of the 143 bleeds treated with one injection.

For perioperative management, N9-GP was rated as excellent or good for 13 surgeries, for a success rate of 100%.

Patients received a preoperative dose of 80 IU/kg. No patient required additional doses on the day of surgery.

During the postoperative period, patients required additional 40 IU/kg doses. The mean total consumption of factor in the pre- and postoperative period was 241 IU/kg (range, 8 – 460 IU/kg.

No unexpected postoperative bleeding occurred.

For full prescribing information, see the package insert. 

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

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

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

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

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

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

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel. 

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel. 

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel.