Pharmacy

Antihemophilic factor

The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.

The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.

The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Antihemophilic factor

The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.

The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.

The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Antihemophilic factor

The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.

The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.

The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.

LEOPOLD I

LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.

The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD II

LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).

The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.

LEOPOLD Kids

LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.

For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.

Safety results

For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.

The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.

The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).

None of the patients developed factor VIII inhibitors.

Prescription medications

Photo courtesy of the CDC

The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.

The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.

This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.

Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.

Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.

Trial results

The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.

Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.

The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.

The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.

At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).

Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).

The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).

Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.

Prescription medications

Photo courtesy of the CDC

The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.

The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.

This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.

Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.

Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.

Trial results

The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.

Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.

The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.

The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.

At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).

Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).

The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).

Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.

Prescription medications

Photo courtesy of the CDC

The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.

The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.

This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.

Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.

Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.

Trial results

The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.

Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.

The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.

The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.

At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).

Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).

The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).

Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for midostaurin (PKC412) to treat acute myeloid leukemia (AML).

Midostaurin is a multi-targeted kinase inhibitor being developed for adults with newly diagnosed AML who are FLT3-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

Breakthrough therapy designation is intended to expedite the development and review of new medicines intended to treat serious or life-threatening conditions. The therapy must demonstrate substantial improvement over an available therapy on at least one clinically significant endpoint.

The designation includes all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.

Phase 3 trial

The breakthrough designation for midostaurin is primarily based on the results of the phase 3 RATIFY trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 717 patients with newly diagnosed, FLT3-positive AML who were younger than 60 at enrollment. All of the patients received standard induction and consolidation therapy. Roughly half also received midostaurin (n=360), while the other half received placebo (n=357).

Patients who received midostaurin experienced a significant improvement in overall survival (hazard ratio=0.77, P=0.0074). The median overall survival was 74.4 months in the midostaurin arm and 25.6 months in the placebo arm.

The median event-free survival was 8 months in the midostaurin arm and 3.6 months in the placebo arm (P=0.0032). The 5-year event-free survival was 27.5% for midostaurin and 19.3% for placebo.

There was no significant difference between the treatment arms with regard to most non-hematologic grade 3/4 adverse events. The exception was rash/desquamation, which occurred in 13% of patients in the midostaurin arm and 8% of patients in the placebo arm (P=0.02).

Other grade 3/4 non-hematologic events occurring in 10% of patients or more included, in the midostaurin and placebo arms, respectively: febrile neutropenia (81%, 82%), infection (40%, 38%), diarrhea (15%, 16%), hypokalemia (13%, 17%), pain (13%, 13%), other infection (12%, 12%), ALT/SGPT (12%, 9%), and fatigue (9%, 11%).

There were 18 deaths (5%) in the midostaurin arm and 19 (5.3%) in the placebo arm during induction and consolidation.

Midostaurin development

Novartis has opened a Global Individual Patient Program (compassionate use program) and a US Expanded Treatment Protocol (ETP) to enable midostaurin access. Patients 18 years of age and older with newly diagnosed FLT3-mutated AML who are able to receive standard induction and consolidation therapy will be considered.

To help identify patients who may have a FLT3 mutation and potentially benefit from treatment with midostaurin, Novartis is collaborating with Invivoscribe Technologies, Inc. which is leading regulatory submissions for a companion diagnostic.

Midostaurin is also being investigated for the treatment of aggressive systemic mastocytosis/mast cell leukemia.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for midostaurin (PKC412) to treat acute myeloid leukemia (AML).

Midostaurin is a multi-targeted kinase inhibitor being developed for adults with newly diagnosed AML who are FLT3-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

Breakthrough therapy designation is intended to expedite the development and review of new medicines intended to treat serious or life-threatening conditions. The therapy must demonstrate substantial improvement over an available therapy on at least one clinically significant endpoint.

The designation includes all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.

Phase 3 trial

The breakthrough designation for midostaurin is primarily based on the results of the phase 3 RATIFY trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 717 patients with newly diagnosed, FLT3-positive AML who were younger than 60 at enrollment. All of the patients received standard induction and consolidation therapy. Roughly half also received midostaurin (n=360), while the other half received placebo (n=357).

Patients who received midostaurin experienced a significant improvement in overall survival (hazard ratio=0.77, P=0.0074). The median overall survival was 74.4 months in the midostaurin arm and 25.6 months in the placebo arm.

The median event-free survival was 8 months in the midostaurin arm and 3.6 months in the placebo arm (P=0.0032). The 5-year event-free survival was 27.5% for midostaurin and 19.3% for placebo.

There was no significant difference between the treatment arms with regard to most non-hematologic grade 3/4 adverse events. The exception was rash/desquamation, which occurred in 13% of patients in the midostaurin arm and 8% of patients in the placebo arm (P=0.02).

Other grade 3/4 non-hematologic events occurring in 10% of patients or more included, in the midostaurin and placebo arms, respectively: febrile neutropenia (81%, 82%), infection (40%, 38%), diarrhea (15%, 16%), hypokalemia (13%, 17%), pain (13%, 13%), other infection (12%, 12%), ALT/SGPT (12%, 9%), and fatigue (9%, 11%).

There were 18 deaths (5%) in the midostaurin arm and 19 (5.3%) in the placebo arm during induction and consolidation.

Midostaurin development

Novartis has opened a Global Individual Patient Program (compassionate use program) and a US Expanded Treatment Protocol (ETP) to enable midostaurin access. Patients 18 years of age and older with newly diagnosed FLT3-mutated AML who are able to receive standard induction and consolidation therapy will be considered.

To help identify patients who may have a FLT3 mutation and potentially benefit from treatment with midostaurin, Novartis is collaborating with Invivoscribe Technologies, Inc. which is leading regulatory submissions for a companion diagnostic.

Midostaurin is also being investigated for the treatment of aggressive systemic mastocytosis/mast cell leukemia.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for midostaurin (PKC412) to treat acute myeloid leukemia (AML).

Midostaurin is a multi-targeted kinase inhibitor being developed for adults with newly diagnosed AML who are FLT3-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

Breakthrough therapy designation is intended to expedite the development and review of new medicines intended to treat serious or life-threatening conditions. The therapy must demonstrate substantial improvement over an available therapy on at least one clinically significant endpoint.

The designation includes all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.

Phase 3 trial

The breakthrough designation for midostaurin is primarily based on the results of the phase 3 RATIFY trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 717 patients with newly diagnosed, FLT3-positive AML who were younger than 60 at enrollment. All of the patients received standard induction and consolidation therapy. Roughly half also received midostaurin (n=360), while the other half received placebo (n=357).

Patients who received midostaurin experienced a significant improvement in overall survival (hazard ratio=0.77, P=0.0074). The median overall survival was 74.4 months in the midostaurin arm and 25.6 months in the placebo arm.

The median event-free survival was 8 months in the midostaurin arm and 3.6 months in the placebo arm (P=0.0032). The 5-year event-free survival was 27.5% for midostaurin and 19.3% for placebo.

There was no significant difference between the treatment arms with regard to most non-hematologic grade 3/4 adverse events. The exception was rash/desquamation, which occurred in 13% of patients in the midostaurin arm and 8% of patients in the placebo arm (P=0.02).

Other grade 3/4 non-hematologic events occurring in 10% of patients or more included, in the midostaurin and placebo arms, respectively: febrile neutropenia (81%, 82%), infection (40%, 38%), diarrhea (15%, 16%), hypokalemia (13%, 17%), pain (13%, 13%), other infection (12%, 12%), ALT/SGPT (12%, 9%), and fatigue (9%, 11%).

There were 18 deaths (5%) in the midostaurin arm and 19 (5.3%) in the placebo arm during induction and consolidation.

Midostaurin development

Novartis has opened a Global Individual Patient Program (compassionate use program) and a US Expanded Treatment Protocol (ETP) to enable midostaurin access. Patients 18 years of age and older with newly diagnosed FLT3-mutated AML who are able to receive standard induction and consolidation therapy will be considered.

To help identify patients who may have a FLT3 mutation and potentially benefit from treatment with midostaurin, Novartis is collaborating with Invivoscribe Technologies, Inc. which is leading regulatory submissions for a companion diagnostic.

Midostaurin is also being investigated for the treatment of aggressive systemic mastocytosis/mast cell leukemia.

Micrograph showing PV

Image courtesy of AFIP

Health Canada has approved the JAK1/2 inhibitor ruxolitinib (Jakavi) for the control of hematocrit in adult patients with polycythemia vera (PV) that is resistant to or intolerant of a cytoreductive agent.

Ruxolitinib is the first targeted treatment approved to treat PV in Canada.

The approval is based on results of the phase 3 RESPONSE trial, which showed that ruxolitinib could provide hematocrit control without phlebotomy in patients with PV.

For RESPONSE, researchers compared ruxolitinib to best available therapy (BAT) for PV. The trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from weeks 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

The primary endpoint was met by significantly more patients in the ruxolitinib arm than the BAT arm— 20.9% and 0.9%, respectively (P<0.0001).

Sixty percent of patients in the ruxolitinib arm achieved hematocrit control, as did 19.6% of patients in the BAT arm. The percentage of patients who had at least a 35% reduction in spleen volume was 38.2% in the ruxolitinib arm and 0.9% in the BAT arm.

The proportion of patients achieving a complete hematologic remission at week 32 was 23.6% in the ruxolitinib arm and 8.9% in the BAT arm (P=0.0028). The proportion of patients achieving a durable primary response at week 48 was 19.1% in the ruxolitinib arm and 0.9% in the BAT arm (P<0.0001).

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued ruxolitinib due to adverse events.

Micrograph showing PV

Image courtesy of AFIP

Health Canada has approved the JAK1/2 inhibitor ruxolitinib (Jakavi) for the control of hematocrit in adult patients with polycythemia vera (PV) that is resistant to or intolerant of a cytoreductive agent.

Ruxolitinib is the first targeted treatment approved to treat PV in Canada.

The approval is based on results of the phase 3 RESPONSE trial, which showed that ruxolitinib could provide hematocrit control without phlebotomy in patients with PV.

For RESPONSE, researchers compared ruxolitinib to best available therapy (BAT) for PV. The trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from weeks 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

The primary endpoint was met by significantly more patients in the ruxolitinib arm than the BAT arm— 20.9% and 0.9%, respectively (P<0.0001).

Sixty percent of patients in the ruxolitinib arm achieved hematocrit control, as did 19.6% of patients in the BAT arm. The percentage of patients who had at least a 35% reduction in spleen volume was 38.2% in the ruxolitinib arm and 0.9% in the BAT arm.

The proportion of patients achieving a complete hematologic remission at week 32 was 23.6% in the ruxolitinib arm and 8.9% in the BAT arm (P=0.0028). The proportion of patients achieving a durable primary response at week 48 was 19.1% in the ruxolitinib arm and 0.9% in the BAT arm (P<0.0001).

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued ruxolitinib due to adverse events.

Micrograph showing PV

Image courtesy of AFIP

Health Canada has approved the JAK1/2 inhibitor ruxolitinib (Jakavi) for the control of hematocrit in adult patients with polycythemia vera (PV) that is resistant to or intolerant of a cytoreductive agent.

Ruxolitinib is the first targeted treatment approved to treat PV in Canada.

The approval is based on results of the phase 3 RESPONSE trial, which showed that ruxolitinib could provide hematocrit control without phlebotomy in patients with PV.

For RESPONSE, researchers compared ruxolitinib to best available therapy (BAT) for PV. The trial was sponsored by Incyte Corporation and Novartis Pharmaceuticals, the companies developing ruxolitinib.

The study’s primary endpoint was the proportion of patients who achieved hematocrit control and were not eligible for phlebotomy from weeks 8 through 32 (with no more than 1 instance of phlebotomy eligibility between randomization and week 8) and who saw a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.

The primary endpoint was met by significantly more patients in the ruxolitinib arm than the BAT arm— 20.9% and 0.9%, respectively (P<0.0001).

Sixty percent of patients in the ruxolitinib arm achieved hematocrit control, as did 19.6% of patients in the BAT arm. The percentage of patients who had at least a 35% reduction in spleen volume was 38.2% in the ruxolitinib arm and 0.9% in the BAT arm.

The proportion of patients achieving a complete hematologic remission at week 32 was 23.6% in the ruxolitinib arm and 8.9% in the BAT arm (P=0.0028). The proportion of patients achieving a durable primary response at week 48 was 19.1% in the ruxolitinib arm and 0.9% in the BAT arm (P<0.0001).

At 80 weeks, the most common adverse events in the ruxolitinib arm were headache (22%), diarrhea (20%), pruritus (20%), and fatigue (17%). Grade 3 or 4 anemia and thrombocytopenia occurred in 2% and 6% of patients, respectively. Five percent of patients discontinued ruxolitinib due to adverse events.

Micrograph showing MF

The US Food and Drug Administration (FDA) has placed a full clinical hold on trials conducted under the investigational new drug application for pacritinib, a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The hold means all patients currently on pacritinib must stop taking the drug immediately, and no patients can be enrolled on a pacritinib trial or start pacritinib as initial or crossover treatment.

In addition, CTI BioPharma has withdrawn the new drug application for pacritinib while the company reviews data from the phase 3 PERSIST-2 trial.

The FDA’s decision to place a full clinical hold on pacritinib trials was due to interim results from PERSIST-2. The aim of this trial was to compare pacritinib to best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The overall survival results from PERSIST-2 indicate that pacritinib had a detrimental effect on survival, which is consistent with results from the PERSIST-1 trial. The deaths in pacritinib-treated patients on PERSIST-2 include intracranial hemorrhage, cardiac failure, and cardiac arrest.

Based on these results, the FDA has made recommendations for CTI BioPharma that supersede the agency’s previous recommendations.

On February 4, 2016, the FDA placed a partial clinical hold on pacritinib trials and made related recommendations for CTI BioPharma, advising that the company modify trial protocols and take other actions in compliance with the partial clinical hold.

Now that pacritinib trials are on full clinical hold, the FDA is recommending that CTI BioPharma conduct dose exploration studies for pacritinib in patients with MF and submit final study reports and datasets for PERSIST-1 and PERSIST-2.

The FDA is also recommending that CTI BioPharma provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, make certain modifications to protocols, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma said all clinical investigators worldwide have been notified of the hold.

Micrograph showing MF

The US Food and Drug Administration (FDA) has placed a full clinical hold on trials conducted under the investigational new drug application for pacritinib, a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The hold means all patients currently on pacritinib must stop taking the drug immediately, and no patients can be enrolled on a pacritinib trial or start pacritinib as initial or crossover treatment.

In addition, CTI BioPharma has withdrawn the new drug application for pacritinib while the company reviews data from the phase 3 PERSIST-2 trial.

The FDA’s decision to place a full clinical hold on pacritinib trials was due to interim results from PERSIST-2. The aim of this trial was to compare pacritinib to best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The overall survival results from PERSIST-2 indicate that pacritinib had a detrimental effect on survival, which is consistent with results from the PERSIST-1 trial. The deaths in pacritinib-treated patients on PERSIST-2 include intracranial hemorrhage, cardiac failure, and cardiac arrest.

Based on these results, the FDA has made recommendations for CTI BioPharma that supersede the agency’s previous recommendations.

On February 4, 2016, the FDA placed a partial clinical hold on pacritinib trials and made related recommendations for CTI BioPharma, advising that the company modify trial protocols and take other actions in compliance with the partial clinical hold.

Now that pacritinib trials are on full clinical hold, the FDA is recommending that CTI BioPharma conduct dose exploration studies for pacritinib in patients with MF and submit final study reports and datasets for PERSIST-1 and PERSIST-2.

The FDA is also recommending that CTI BioPharma provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, make certain modifications to protocols, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma said all clinical investigators worldwide have been notified of the hold.

Micrograph showing MF

The US Food and Drug Administration (FDA) has placed a full clinical hold on trials conducted under the investigational new drug application for pacritinib, a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The hold means all patients currently on pacritinib must stop taking the drug immediately, and no patients can be enrolled on a pacritinib trial or start pacritinib as initial or crossover treatment.

In addition, CTI BioPharma has withdrawn the new drug application for pacritinib while the company reviews data from the phase 3 PERSIST-2 trial.

The FDA’s decision to place a full clinical hold on pacritinib trials was due to interim results from PERSIST-2. The aim of this trial was to compare pacritinib to best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The overall survival results from PERSIST-2 indicate that pacritinib had a detrimental effect on survival, which is consistent with results from the PERSIST-1 trial. The deaths in pacritinib-treated patients on PERSIST-2 include intracranial hemorrhage, cardiac failure, and cardiac arrest.

Based on these results, the FDA has made recommendations for CTI BioPharma that supersede the agency’s previous recommendations.

On February 4, 2016, the FDA placed a partial clinical hold on pacritinib trials and made related recommendations for CTI BioPharma, advising that the company modify trial protocols and take other actions in compliance with the partial clinical hold.

Now that pacritinib trials are on full clinical hold, the FDA is recommending that CTI BioPharma conduct dose exploration studies for pacritinib in patients with MF and submit final study reports and datasets for PERSIST-1 and PERSIST-2.

The FDA is also recommending that CTI BioPharma provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, make certain modifications to protocols, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma said all clinical investigators worldwide have been notified of the hold.

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Micrograph showing primary MF

The US Food and Drug Administration (FDA) has placed a partial clinical hold on trials conducted under the investigational new drug

(IND) application for pacritinib.

Pacritinib is a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).

The partial clinical hold impacts part of the clinical work currently being conducted under the pacritinib IND and will also affect planned clinical trials.

The FDA said the reasons for the partial clinical hold are excess mortality and other adverse events in pacritinib-treated patients (compared to the control arm) in the PERSIST-1 trial.

The excess mortality was most evident during the non-randomized crossover period following the initial 24 weeks of randomized treatment, during which patients in the control arm could switch to pacritinib treatment.

Under the partial clinical hold, investigators may not enroll new patients or start pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment must stop using pacritinib.

In addition, the FDA has recommended that CTI BioPharma make certain modifications to protocols, provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, and take certain other actions.

CTI BioPharma said it intends to implement the FDA’s recommendations, and all clinical investigators worldwide have been notified of the partial clinical hold.

Just before the FDA notified CTI BioPharma of the partial clinical hold, the company completed enrollment in the phase 3 PERSIST-2 trial.

In PERSIST-2, researchers are comparing the efficacy and safety of pacritinib and best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

Under the partial clinical hold, patients on this trial who are currently receiving pacritinib may continue to do so unless they are not deriving benefit after 30 weeks of pacritinib treatment, and crossover of patients from the control arm to the pacritinib arm will not be allowed.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient receiving chemotherapy

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved a supplemental new drug application for single-dose fosaprepitant dimeglumine (Emend) for injection.

The agency approved the substance P/neurokinin-1 (NK1) receptor antagonist for use in combination with other anti-emetic medicines to prevent delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC).

This makes fosaprepitant dimeglumine the first intravenous NK1 receptor antagonist approved in the US for patients receiving either highly emetogenic chemotherapy or MEC.

Fosaprepitant dimeglumine has not been studied for the treatment of established nausea and vomiting.

The FDA’s latest approval of fosaprepitant dimeglumine is supported by data from a phase 3 study published in the Annals of Oncology.

Patients receiving MEC were given ondansetron and dexamethasone (n=498) or ondansetron and dexamethasone plus a single intravenous infusion of fosaprepitant dimeglumine (n=502).

The primary endpoint was complete response (CR)—defined as no vomiting and no use of rescue therapy—in the delayed phase of chemotherapy-induced nausea and vomiting, which is 25 to 120 hours after the initiation of chemotherapy.

Secondary endpoints included CR in the overall and acute phases—0 to 120 and 0 to 24 hours after MEC initiation, respectively—and no vomiting in the overall phase.

The fosaprepitant regimen improved CR significantly in the delayed and overall phases but not in the acute phase.

In the delayed phase, the CR rate was 78.9% with the fosaprepitant regimen and 68.5% with the control regimen (P<0.001). In the acute phase, the CR rate was 93.2% and 91.0%, respectively (P=0.184). Overall, the CR rate was 77.1% and 66.9%, respectively (P<0.001).

In the overall phase, the proportion of subjects with no vomiting was 82.7% with the fosaprepitant regimen and 72.9% with the control regimen (P<0.001). The proportion of patients with no significant nausea was 83.2% and 77.9%, respectively (P=0.030).

The most common adverse events reported in the fosaprepitant and control arms, respectively, were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

Fosaprepitant dimeglumine is a product of Merck. For more details on the drug, see the prescribing information.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.

Patient consults pharmacist

Photo by Rhoda Baer

Sun Pharma has announced the US launch of imatinib mesylate tablets, which are a generic version of Novartis’s Gleevec, for indications approved by the US Food and Drug Administration (FDA).

As part of this launch, Sun Pharma has rolled out a savings card program. The goal is to provide greater access to imatinib mesylate tablets for patients who have commercial insurance, but their out-of-pocket cost may exceed an affordable amount.

Sun Pharma’s Imatinib Mesylate Savings Card will reduce patient’s co-payment to $10. The card will also offer patients an additional savings benefit of up to $700 for a 30-day fill to offset any additional out-of-pocket cost should they be required to meet their deductible or co-insurance.

Participating pharmacies across the US can use the patient’s card as part of this program.

Eligible patients can participate in Sun Pharma’s Imatinib Mesylate Savings Card program by registering at www.imatinibrx.com or by requesting a savings card from their oncologist. Sun Pharma will be supplying its Imatinib Mesylate Savings Cards to more than 4500 oncologists.

Sun Pharma has established a Hub service so patients can call and speak with a trained healthcare professional about imatinib mesylate. The number is 1-844-502-5950.

In addition, qualifying patients can receive Sun Pharma’s imatinib mesylate at no cost. Based on qualifications for applying and including a doctor’s prescription, the Hub service will determine if a patient is qualified to receive imatinib mesylate for free. Upon acceptance, the prescription will be processed and delivered to the qualifying patient at no cost.

Sun Pharma’s imatinib mesylate was approved by the FDA in December 2015 and was granted 180 days of marketing exclusivity from the time of its launch. The drug is available in 100 mg and 400 mg tablets.

It is approved to treat:

• Newly diagnosed adult and pediatric patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• Patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy
• Adults with relapsed or refractory Ph+ acute lymphoblastic leukemia
• Adults with myelodysplastic/myeloproliferative diseases associated with PDGFR gene re-arrangements
• Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown
• Adults with hypereosinophilic syndrome and/or chronic eosinophilic leukemia, including those who have the FIP1L1-PDGFRα fusion kinase
• Adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans.

Sun Pharma’s imatinib mesylate is not approved to treat patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.