Pharmacy

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.

Elotuzumab is the first immunostimulatory antibody approved for MM.

Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.

Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.

The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.

ELOQUENT-2 trial

The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.

Elotuzumab is the first immunostimulatory antibody approved for MM.

Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.

Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.

The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.

ELOQUENT-2 trial

The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has approved elotuzumab (Empliciti) for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received 1 to 3 prior therapies.

Elotuzumab is an immunostimulatory antibody that specifically targets signaling lymphocyte activation molecule family member 7 (SLAMF7), a cell-surface glycoprotein that is expressed on myeloma cells independent of cytogenetic abnormalities.

Elotuzumab is the first immunostimulatory antibody approved for MM.

Bristol-Myers Squibb said it expects to begin shipping elotuzumab this week. The drug will be available for injection for intravenous use in 300 mg and 400 mg vials.

Elotuzumab is currently under review by the European Medicines Agency and has been granted accelerated assessment.

The FDA previously granted elotuzumab breakthrough therapy designation, orphan drug designation, and priority review.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities. For more details on the drug, see the full prescribing information.

ELOQUENT-2 trial

The FDA’s approval of elotuzumab is primarily based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent serious adverse events in each arm, respectively, were pneumonia (15.4% vs 11%), pyrexia (6.9% vs 4.7%), respiratory tract infection (3.1% vs 1.3%), anemia (2.8% vs 1.9%), pulmonary embolism (3.1% vs 2.5%), and acute renal failure (2.5% vs 1.9%).

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.

Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.

The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.

Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
• Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
  

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.

Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.

The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.

Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
• Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
  

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

The European Commission (EC) has granted marketing authorization for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The EC’s decision applies to the 28 countries of the European Union (EU) as well as Iceland, Lichtenstein, and Norway.

Idarucizumab is the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant to be approved for use in the EU. The drug was approved in the US last month.

The EC’s decision to approve idarucizumab was based on results in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.

In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well-tolerated.

In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Boehringer Ingelheim, the company developing idarucizumab, said it is committed to making the drug available as widely as possible and will launch idarucizumab in European countries as soon as national requirements allow.

Boehringer Ingelheim is also the maker of dabigatran, which is currently approved in the EU for the following indications:

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
• Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
• Treatment of deep vein thrombosis and pulmonary embolism and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults.
  

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).

This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

About blinatumomab

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.

BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.

Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.

The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.

Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is being developed by Amgen.

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).

This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

About blinatumomab

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.

BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.

Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.

The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.

Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is being developed by Amgen.

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The European Commission (EC) has granted conditional marketing authorization for blinatumomab (Blincyto) to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).

This applies to the 28 member countries of the European Union as well as Iceland, Lichtenstein, and Norway.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.

Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.

The EC granted conditional marketing authorization for blinatumomab based on a pair of phase 2 trials—Study ‘211 and Study ‘206.

Study ‘211

Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.

The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.

According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).

Study ‘206

Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.

In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).

The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).

However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.

About blinatumomab

Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.

BiTE antibody constructs are intended to help the immune system detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells.

BiTE antibody constructs help place the T cells within reach of the targeted cells, with the intent of allowing T cells to inject toxins and trigger apoptosis in the cancer cells.

Blinatumomab was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.

The drug was granted breakthrough therapy designation and priority review by the US Food and Drug Administration.

Blinatumomab has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is being developed by Amgen.

Antihemophilic factor

The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.

Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.

Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.

Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.

The product is expected to launch in initial EU countries in early 2016.

The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

About efmoroctocog alfa

Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.

Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.

Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.

Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.

Antihemophilic factor

The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.

Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.

Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.

Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.

The product is expected to launch in initial EU countries in early 2016.

The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

About efmoroctocog alfa

Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.

Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.

Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.

Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.

Antihemophilic factor

The European Commission (EC) has approved the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A in the European Union (EU) as well as Iceland, Liechtenstein, and Norway.

Efmoroctocog alfa is indicated for both on-demand and prophylactic treatment of hemophilia A in patients of all ages.

Research has shown that efmoroctocog alfa has an extended half-life compared to recombinant factor VIII.

Efmoroctocog alfa will be the first hemophilia A treatment in the EU to offer prolonged protection against bleeding episodes with prophylactic injections every 3 to 5 days.

The product is expected to launch in initial EU countries in early 2016.

The EC’s approval of efmoroctocog alfa was based on data from 2 phase 3 studies: A-LONG and Kids A-LONG.

A-LONG

The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.

Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.

None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with recombinant factor VIII.

Kids A-LONG

The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to factor VIII therapies.

The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.

None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.

ASPIRE

Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.

Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.

About efmoroctocog alfa

Efmoroctocog alfa was developed by fusing B-domain deleted factor VIII to the Fc portion of immunoglobulin G subclass 1. It is believed that this enables efmoroctocog alfa to utilize a naturally occurring pathway to prolong the time the therapy remains in the body.

Sobi and Biogen are collaborators in the development and commercialization of efmoroctocog alfa for hemophilia A.

Last year, Sobi exercised its opt-in right to assumeefmoroctocog alfa’s final development and commercialization in pre-specified territories, which includes Europe, North Africa, Russia, and certain countries in the Middle East.

Biogen leads development and manufacturing of the product and holds commercialization rights in North America and all other regions in the world outside of the Sobi territories.

Elocta is the trade name for efmoroctocog alfa in Sobi’s territory. The product is approved under the name Eloctate (Antihemophilic Factor [Recombinant], Fc Fusion Protein) in the US, Canada, Australia, New Zealand, and Japan.

 

 

Ofatumumab (Arzerra)

Photo courtesy of GSK

 

Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.

The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.

An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.

Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.

“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”

The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m²) by intravenous infusion for 4 weekly doses.

Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.

Past disappointments

This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.

In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.

About ofatumumab

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.

In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).

 

 

Ofatumumab (Arzerra)

Photo courtesy of GSK

 

Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.

The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.

An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.

Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.

“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”

The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m²) by intravenous infusion for 4 weekly doses.

Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.

Past disappointments

This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.

In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.

About ofatumumab

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.

In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).

 

 

Ofatumumab (Arzerra)

Photo courtesy of GSK

 

Genmab A/S said it is stopping a phase 3 trial of ofatumumab in follicular lymphoma (FL) after a planned interim analysis suggested the drug was unlikely to demonstrate superiority over rituximab.

The trial was designed to compare these 2 drugs as single-agent treatment in FL patients who had relapsed at least 6 months after completing treatment with a rituximab-containing regimen.

An interim analysis performed by an independent data monitoring committee indicated that, if the trial was to be completed as planned, it was unlikely that ofatumumab would improve progression-free survival (PFS) when compared to rituximab.

Genmab noted that this analysis did not reveal any new safety signals associated with ofatumumab, and no other ongoing trials of ofatumumab will be affected by the results of this analysis.

“The outcome of the interim analysis in this study is disappointing, as we had hoped to see superiority of ofatumumab,” said Jan van de Winkel, PhD, chief executive officer of Genmab. “The data from the study will now be prepared so that it can be presented at a future scientific conference.”

The goal of the study was to randomize up to 516 patients to receive ofatumumab (at 1000 mg) or rituximab (at 375 mg/m²) by intravenous infusion for 4 weekly doses.

Patients who had stable or responsive disease would then receive single infusions of ofatumumab or rituximab every 2 months for 4 additional doses—a total of 8 doses over 9 months. The primary endpoint of the study was PFS.

Past disappointments

This is not the first time ofatumumab has fallen short of expectations. Last year, the drug failed to meet the primary endpoint in two phase 3 trials.

In the OMB114242 trial, ofatumumab failed to improve PFS when compared to physicians’ choice in patients with bulky, fludarabine-refractory chronic lymphocytic leukemia (CLL).

In the ORCHARRD trial, ofatumumab plus chemotherapy failed to improve PFS when compared to rituximab plus chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma.

About ofatumumab

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.

In the US, ofatumumab is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

In the European Union (EU), ofatumumab is approved for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

In more than 50 countries worldwide, including the US and EU member countries, ofatumumab is approved as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis (formerly GSK).

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).

The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.

If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.

First-line ALL

Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.

Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.

Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).

Previously treated ALL

Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).

Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.

These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).

Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.

Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.

The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).

For more details on these trials and pegaspargase, see the product information.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).

The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.

If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.

First-line ALL

Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.

Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.

Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).

Previously treated ALL

Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).

Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.

These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).

Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.

Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.

The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).

For more details on these trials and pegaspargase, see the product information.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for pegaspargase (Oncaspar) as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).

The CHMP’s opinion has been referred to the European Commission, which grants marketing authorization for drugs in the European Union.

If approved, pegaspargase will be marketed for the aforementioned indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.

Baxalta Incorporated, the company developing pegaspargase, expects a decision from the European Commission early next year.

First-line ALL

Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.

Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.

Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).

Previously treated ALL

Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).

Patients received pegaspargase as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses.

These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E coli L-asparaginase-containing re-induction chemotherapy. However, antitumor activity was observed with single-agent pegaspargase as well (3 responses).

Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or in combination with multi-agent chemotherapy.

Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.

The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).

For more details on these trials and pegaspargase, see the product information.

Dabigatran (Pradaxa)

Photo by ec-jpr

The US Food and Drug Administration (FDA) has approved the direct thrombin inhibitor dabigatran etexilate mesylate (Pradaxa) for the prophylaxis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have undergone hip replacement surgery.

Dabigatran was initially approved by the FDA in 2010 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

In 2014, dabigatran was approved to treat DVT and PE in patients who have been treated with a parenteral anticoagulant for 5 to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.

A reversal agent for dabigatran, known as idarucizumab (Praxbind), was approved by the FDA last month.

Trial data

The latest approval of dabigatran is based on results of 2 randomized, double-blind, phase 3 trials in patients undergoing total hip replacement, RE-NOVATE™ and RE-NOVATE II™.

In the RE-NOVATE trial, 3494 patients were randomized to 3 groups receiving prophylactic treatment with 1 of 2 doses of dabigatran (220 mg or 150 mg) once daily or enoxaparin at 40 mg once daily for 28 to 35 days.

The first dabigatran group was given a dose of 110 mg on the day of surgery and 220 mg daily thereafter. The second dabigatran group received a dose of 75 mg on the day of surgery and 150 mg daily thereafter.

Patients taking dabigatran at 220 mg had a lower composite total of venous thromboembolism (VTE) and all-cause death (6.0%) than patients on enoxaparin (6.7%). However, the rate of major bleeding was higher with dabigatran at 220 mg (2.0%) than with enoxaparin (1.6%).

In the RE-NOVATE II trial, 2055 patients were randomized to prophylactic treatment for 28 to 35 days with dabigatran at 220 mg once daily or enoxaparin at 40 mg once daily. Patients receiving dabigatran were treated with a dose of 110 mg on the day of surgery and 220 mg daily thereafter.

The composite total of VTE and all-cause death occurred in 7.7% of patients in the dabigatran group and 8.8% of patients in the enoxaparin group. Again, the rate of major bleeding was higher with dabigatran at 220 mg (1.4%) than with enoxaparin (0.9%).

In both studies, the rate of major gastrointestinal bleeds in patients receiving dabigatran and enoxaparin was the same (0.1%). The rate of any gastrointestinal bleeds was 1.4% for dabigatran and 0.9% for enoxaparin.

The most common adverse events in both studies were gastrointestinal disorders. The incidence was the same across the dabigatran and enoxaparin treatment groups (39.5%).

Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) occurred more frequently in patients receiving dabigatran (4.1%) than enoxaparin (3.8%).

Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis, and gastric hemorrhage) were less common in patients receiving dabigatran (0.6%) than enoxaparin (1.0%). Clinical myocardial infarction was reported in 2 (0.1%) dabigatran patients and 6 (0.3%) enoxaparin patients.

Dabigatran is marketed as Pradaxa by Boehringer Ingelheim. For more details on the drug, see the prescribing information.

Dabigatran (Pradaxa)

Photo by ec-jpr

The US Food and Drug Administration (FDA) has approved the direct thrombin inhibitor dabigatran etexilate mesylate (Pradaxa) for the prophylaxis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have undergone hip replacement surgery.

Dabigatran was initially approved by the FDA in 2010 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

In 2014, dabigatran was approved to treat DVT and PE in patients who have been treated with a parenteral anticoagulant for 5 to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.

A reversal agent for dabigatran, known as idarucizumab (Praxbind), was approved by the FDA last month.

Trial data

The latest approval of dabigatran is based on results of 2 randomized, double-blind, phase 3 trials in patients undergoing total hip replacement, RE-NOVATE™ and RE-NOVATE II™.

In the RE-NOVATE trial, 3494 patients were randomized to 3 groups receiving prophylactic treatment with 1 of 2 doses of dabigatran (220 mg or 150 mg) once daily or enoxaparin at 40 mg once daily for 28 to 35 days.

The first dabigatran group was given a dose of 110 mg on the day of surgery and 220 mg daily thereafter. The second dabigatran group received a dose of 75 mg on the day of surgery and 150 mg daily thereafter.

Patients taking dabigatran at 220 mg had a lower composite total of venous thromboembolism (VTE) and all-cause death (6.0%) than patients on enoxaparin (6.7%). However, the rate of major bleeding was higher with dabigatran at 220 mg (2.0%) than with enoxaparin (1.6%).

In the RE-NOVATE II trial, 2055 patients were randomized to prophylactic treatment for 28 to 35 days with dabigatran at 220 mg once daily or enoxaparin at 40 mg once daily. Patients receiving dabigatran were treated with a dose of 110 mg on the day of surgery and 220 mg daily thereafter.

The composite total of VTE and all-cause death occurred in 7.7% of patients in the dabigatran group and 8.8% of patients in the enoxaparin group. Again, the rate of major bleeding was higher with dabigatran at 220 mg (1.4%) than with enoxaparin (0.9%).

In both studies, the rate of major gastrointestinal bleeds in patients receiving dabigatran and enoxaparin was the same (0.1%). The rate of any gastrointestinal bleeds was 1.4% for dabigatran and 0.9% for enoxaparin.

The most common adverse events in both studies were gastrointestinal disorders. The incidence was the same across the dabigatran and enoxaparin treatment groups (39.5%).

Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) occurred more frequently in patients receiving dabigatran (4.1%) than enoxaparin (3.8%).

Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis, and gastric hemorrhage) were less common in patients receiving dabigatran (0.6%) than enoxaparin (1.0%). Clinical myocardial infarction was reported in 2 (0.1%) dabigatran patients and 6 (0.3%) enoxaparin patients.

Dabigatran is marketed as Pradaxa by Boehringer Ingelheim. For more details on the drug, see the prescribing information.

Dabigatran (Pradaxa)

Photo by ec-jpr

The US Food and Drug Administration (FDA) has approved the direct thrombin inhibitor dabigatran etexilate mesylate (Pradaxa) for the prophylaxis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have undergone hip replacement surgery.

Dabigatran was initially approved by the FDA in 2010 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

In 2014, dabigatran was approved to treat DVT and PE in patients who have been treated with a parenteral anticoagulant for 5 to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.

A reversal agent for dabigatran, known as idarucizumab (Praxbind), was approved by the FDA last month.

Trial data

The latest approval of dabigatran is based on results of 2 randomized, double-blind, phase 3 trials in patients undergoing total hip replacement, RE-NOVATE™ and RE-NOVATE II™.

In the RE-NOVATE trial, 3494 patients were randomized to 3 groups receiving prophylactic treatment with 1 of 2 doses of dabigatran (220 mg or 150 mg) once daily or enoxaparin at 40 mg once daily for 28 to 35 days.

The first dabigatran group was given a dose of 110 mg on the day of surgery and 220 mg daily thereafter. The second dabigatran group received a dose of 75 mg on the day of surgery and 150 mg daily thereafter.

Patients taking dabigatran at 220 mg had a lower composite total of venous thromboembolism (VTE) and all-cause death (6.0%) than patients on enoxaparin (6.7%). However, the rate of major bleeding was higher with dabigatran at 220 mg (2.0%) than with enoxaparin (1.6%).

In the RE-NOVATE II trial, 2055 patients were randomized to prophylactic treatment for 28 to 35 days with dabigatran at 220 mg once daily or enoxaparin at 40 mg once daily. Patients receiving dabigatran were treated with a dose of 110 mg on the day of surgery and 220 mg daily thereafter.

The composite total of VTE and all-cause death occurred in 7.7% of patients in the dabigatran group and 8.8% of patients in the enoxaparin group. Again, the rate of major bleeding was higher with dabigatran at 220 mg (1.4%) than with enoxaparin (0.9%).

In both studies, the rate of major gastrointestinal bleeds in patients receiving dabigatran and enoxaparin was the same (0.1%). The rate of any gastrointestinal bleeds was 1.4% for dabigatran and 0.9% for enoxaparin.

The most common adverse events in both studies were gastrointestinal disorders. The incidence was the same across the dabigatran and enoxaparin treatment groups (39.5%).

Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) occurred more frequently in patients receiving dabigatran (4.1%) than enoxaparin (3.8%).

Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis, and gastric hemorrhage) were less common in patients receiving dabigatran (0.6%) than enoxaparin (1.0%). Clinical myocardial infarction was reported in 2 (0.1%) dabigatran patients and 6 (0.3%) enoxaparin patients.

Dabigatran is marketed as Pradaxa by Boehringer Ingelheim. For more details on the drug, see the prescribing information.

 

 

Prescription medications

Photo by Steven Harbour

 

Health experts are calling on US lawmakers and regulators to “close loopholes” in the Orphan Drug Act.

The experts say the loopholes can provide pharmaceutical companies with millions of dollars in unintended subsidies and tax breaks and fuel skyrocketing medication costs.

They argue that companies are exploiting gaps in the law by claiming orphan status for drugs that end up being marketed for more common conditions.

“The industry has been gaming the system by slicing and dicing indications so that drugs qualify for lucrative orphan status benefits,” says Martin Makary, MD, of Johns Hopkins Hospital in Baltimore, Maryland.

“As a result, funding support intended for rare disease medicine is diverted to fund the development of blockbuster drugs.”

Dr Makary and his colleagues express this viewpoint in a commentary published in the American Journal of Clinical Oncology.

The US Food and Drug Administration (FDA) grants orphan designation to encourage the development of drugs for diseases that affect fewer than 200,000 people in the US. The Orphan Drug Act was enacted in 1983 to provide incentives for drug companies to develop treatments for so-called orphan diseases that would be unprofitable because of the limited market.

Dr Makary and his colleagues say the legislation has accomplished that mission and sparked the development of life-saving therapies for a range of rare disorders. However, the authors say the law has also invited abuse.

Under the terms of the act, companies can receive federal taxpayer subsidies of up to half a million dollars a year for up to 4 years per drug, large tax credits, and waivers of marketing application fees that can cost more than $2 million. In addition, the FDA can grant companies 7 years of marketing exclusivity for an orphan drug to ensure that companies recoup the costs of research and development.

Dr Makary says companies exploit the law by initially listing only a single indication for a drug’s use—one narrow enough to qualify for orphan disease benefits. After FDA approval, however, some such drugs are marketed and used off-label more broadly, thus turning large profits.

“This is a financially toxic practice that is also unethical,” says study author Michael Daniel, also of Johns Hopkins.

“It’s time to ensure that we also render it illegal. The practice inflates drug prices, and the costs are passed on to consumers in the form of higher health insurance premiums.”

For example, the drug rituximab was originally approved to treat follicular B-cell non-Hodgkin lymphoma, a disease that affects about 14,000 patients a year. Now, rituximab is also used to treat several other types of cancer, organ rejection following kidney transplant, and autoimmune diseases, including rheumatoid arthritis, which affects 1.3 million Americans.

Rituximab, marketed under several trade names, is the top-selling medication approved as an orphan drug, the 12th all-time drug best-seller in the US, and it generated $3.7 billion in domestic sales in 2014.

In fact, 7 of the top 10 best-selling drugs in the US for 2014 came on the market with an orphan designation, according to Dr Makary and his colleagues.

Of the 41 drugs approved by the FDA in 2014, 18 had orphan status designations. The authors predict that, in 2015, orphan drugs will generate sales totaling $107 billion. And that number is expected to reach $176 billion by 2020.

Dr Makary says this projection represents a yearly growth rate of nearly 11%, or double the growth rate of the overall prescription drug market. The authors also cite data showing that, by 2020, orphan drugs are expected to account for 19% of global prescription drug sales, up from 6% in the year 2000.

Although the reasons for this boom in orphan drugs are likely multifactorial, the exploitation of the orphan drug act is an important catalyst behind this trend, the authors say.

Because orphan designation guarantees a 7-year exclusivity deal to market the drug and protects it from generic competition, the price tags for such medications often balloon rapidly.

For example, the drug imatinib was initially priced at $30,000 per year in 2001. By 2012, it cost $92,000 a year.

The drug’s original designation was for chronic myelogenous leukemia, and it would therefore treat 9000 patients a year in the US. Subsequently, imatinib was given 6 additional orphan designations for various conditions, including gastric cancers and immune disorders.

Dr Makary says, in essence, the exclusivity clause guarantees a hyperextended government-sponsored monopoly. So it’s not surprising that the median cost for orphan drugs is more than $98,000 per patient per year, compared with a median cost of just over $5000 per patient per year for drugs without orphan status.

Overall, nearly 15% of already approved orphan drugs subsequently add far more common diseases to their treatment repertoires.

Dr Makary and his colleagues recommend that, once a drug exceeds the basic tenets of the act—to treat fewer than 200,000 people—it should no longer receive government support or marketing exclusivity.

This can be achieved, the authors say, through pricing negotiations, clauses that reduce marketing exclusivity, and leveling of taxes once a medication becomes a blockbuster treatment for conditions not listed in the original FDA approval.

They say such measures would ensure the spirit of the original act is followed while continuing to provide critical economic incentives for truly rare diseases.

 

 

Prescription medications

Photo by Steven Harbour

 

Health experts are calling on US lawmakers and regulators to “close loopholes” in the Orphan Drug Act.

The experts say the loopholes can provide pharmaceutical companies with millions of dollars in unintended subsidies and tax breaks and fuel skyrocketing medication costs.

They argue that companies are exploiting gaps in the law by claiming orphan status for drugs that end up being marketed for more common conditions.

“The industry has been gaming the system by slicing and dicing indications so that drugs qualify for lucrative orphan status benefits,” says Martin Makary, MD, of Johns Hopkins Hospital in Baltimore, Maryland.

“As a result, funding support intended for rare disease medicine is diverted to fund the development of blockbuster drugs.”

Dr Makary and his colleagues express this viewpoint in a commentary published in the American Journal of Clinical Oncology.

The US Food and Drug Administration (FDA) grants orphan designation to encourage the development of drugs for diseases that affect fewer than 200,000 people in the US. The Orphan Drug Act was enacted in 1983 to provide incentives for drug companies to develop treatments for so-called orphan diseases that would be unprofitable because of the limited market.

Dr Makary and his colleagues say the legislation has accomplished that mission and sparked the development of life-saving therapies for a range of rare disorders. However, the authors say the law has also invited abuse.

Under the terms of the act, companies can receive federal taxpayer subsidies of up to half a million dollars a year for up to 4 years per drug, large tax credits, and waivers of marketing application fees that can cost more than $2 million. In addition, the FDA can grant companies 7 years of marketing exclusivity for an orphan drug to ensure that companies recoup the costs of research and development.

Dr Makary says companies exploit the law by initially listing only a single indication for a drug’s use—one narrow enough to qualify for orphan disease benefits. After FDA approval, however, some such drugs are marketed and used off-label more broadly, thus turning large profits.

“This is a financially toxic practice that is also unethical,” says study author Michael Daniel, also of Johns Hopkins.

“It’s time to ensure that we also render it illegal. The practice inflates drug prices, and the costs are passed on to consumers in the form of higher health insurance premiums.”

For example, the drug rituximab was originally approved to treat follicular B-cell non-Hodgkin lymphoma, a disease that affects about 14,000 patients a year. Now, rituximab is also used to treat several other types of cancer, organ rejection following kidney transplant, and autoimmune diseases, including rheumatoid arthritis, which affects 1.3 million Americans.

Rituximab, marketed under several trade names, is the top-selling medication approved as an orphan drug, the 12th all-time drug best-seller in the US, and it generated $3.7 billion in domestic sales in 2014.

In fact, 7 of the top 10 best-selling drugs in the US for 2014 came on the market with an orphan designation, according to Dr Makary and his colleagues.

Of the 41 drugs approved by the FDA in 2014, 18 had orphan status designations. The authors predict that, in 2015, orphan drugs will generate sales totaling $107 billion. And that number is expected to reach $176 billion by 2020.

Dr Makary says this projection represents a yearly growth rate of nearly 11%, or double the growth rate of the overall prescription drug market. The authors also cite data showing that, by 2020, orphan drugs are expected to account for 19% of global prescription drug sales, up from 6% in the year 2000.

Although the reasons for this boom in orphan drugs are likely multifactorial, the exploitation of the orphan drug act is an important catalyst behind this trend, the authors say.

Because orphan designation guarantees a 7-year exclusivity deal to market the drug and protects it from generic competition, the price tags for such medications often balloon rapidly.

For example, the drug imatinib was initially priced at $30,000 per year in 2001. By 2012, it cost $92,000 a year.

The drug’s original designation was for chronic myelogenous leukemia, and it would therefore treat 9000 patients a year in the US. Subsequently, imatinib was given 6 additional orphan designations for various conditions, including gastric cancers and immune disorders.

Dr Makary says, in essence, the exclusivity clause guarantees a hyperextended government-sponsored monopoly. So it’s not surprising that the median cost for orphan drugs is more than $98,000 per patient per year, compared with a median cost of just over $5000 per patient per year for drugs without orphan status.

Overall, nearly 15% of already approved orphan drugs subsequently add far more common diseases to their treatment repertoires.

Dr Makary and his colleagues recommend that, once a drug exceeds the basic tenets of the act—to treat fewer than 200,000 people—it should no longer receive government support or marketing exclusivity.

This can be achieved, the authors say, through pricing negotiations, clauses that reduce marketing exclusivity, and leveling of taxes once a medication becomes a blockbuster treatment for conditions not listed in the original FDA approval.

They say such measures would ensure the spirit of the original act is followed while continuing to provide critical economic incentives for truly rare diseases.

 

 

Prescription medications

Photo by Steven Harbour

 

Health experts are calling on US lawmakers and regulators to “close loopholes” in the Orphan Drug Act.

The experts say the loopholes can provide pharmaceutical companies with millions of dollars in unintended subsidies and tax breaks and fuel skyrocketing medication costs.

They argue that companies are exploiting gaps in the law by claiming orphan status for drugs that end up being marketed for more common conditions.

“The industry has been gaming the system by slicing and dicing indications so that drugs qualify for lucrative orphan status benefits,” says Martin Makary, MD, of Johns Hopkins Hospital in Baltimore, Maryland.

“As a result, funding support intended for rare disease medicine is diverted to fund the development of blockbuster drugs.”

Dr Makary and his colleagues express this viewpoint in a commentary published in the American Journal of Clinical Oncology.

The US Food and Drug Administration (FDA) grants orphan designation to encourage the development of drugs for diseases that affect fewer than 200,000 people in the US. The Orphan Drug Act was enacted in 1983 to provide incentives for drug companies to develop treatments for so-called orphan diseases that would be unprofitable because of the limited market.

Dr Makary and his colleagues say the legislation has accomplished that mission and sparked the development of life-saving therapies for a range of rare disorders. However, the authors say the law has also invited abuse.

Under the terms of the act, companies can receive federal taxpayer subsidies of up to half a million dollars a year for up to 4 years per drug, large tax credits, and waivers of marketing application fees that can cost more than $2 million. In addition, the FDA can grant companies 7 years of marketing exclusivity for an orphan drug to ensure that companies recoup the costs of research and development.

Dr Makary says companies exploit the law by initially listing only a single indication for a drug’s use—one narrow enough to qualify for orphan disease benefits. After FDA approval, however, some such drugs are marketed and used off-label more broadly, thus turning large profits.

“This is a financially toxic practice that is also unethical,” says study author Michael Daniel, also of Johns Hopkins.

“It’s time to ensure that we also render it illegal. The practice inflates drug prices, and the costs are passed on to consumers in the form of higher health insurance premiums.”

For example, the drug rituximab was originally approved to treat follicular B-cell non-Hodgkin lymphoma, a disease that affects about 14,000 patients a year. Now, rituximab is also used to treat several other types of cancer, organ rejection following kidney transplant, and autoimmune diseases, including rheumatoid arthritis, which affects 1.3 million Americans.

Rituximab, marketed under several trade names, is the top-selling medication approved as an orphan drug, the 12th all-time drug best-seller in the US, and it generated $3.7 billion in domestic sales in 2014.

In fact, 7 of the top 10 best-selling drugs in the US for 2014 came on the market with an orphan designation, according to Dr Makary and his colleagues.

Of the 41 drugs approved by the FDA in 2014, 18 had orphan status designations. The authors predict that, in 2015, orphan drugs will generate sales totaling $107 billion. And that number is expected to reach $176 billion by 2020.

Dr Makary says this projection represents a yearly growth rate of nearly 11%, or double the growth rate of the overall prescription drug market. The authors also cite data showing that, by 2020, orphan drugs are expected to account for 19% of global prescription drug sales, up from 6% in the year 2000.

Although the reasons for this boom in orphan drugs are likely multifactorial, the exploitation of the orphan drug act is an important catalyst behind this trend, the authors say.

Because orphan designation guarantees a 7-year exclusivity deal to market the drug and protects it from generic competition, the price tags for such medications often balloon rapidly.

For example, the drug imatinib was initially priced at $30,000 per year in 2001. By 2012, it cost $92,000 a year.

The drug’s original designation was for chronic myelogenous leukemia, and it would therefore treat 9000 patients a year in the US. Subsequently, imatinib was given 6 additional orphan designations for various conditions, including gastric cancers and immune disorders.

Dr Makary says, in essence, the exclusivity clause guarantees a hyperextended government-sponsored monopoly. So it’s not surprising that the median cost for orphan drugs is more than $98,000 per patient per year, compared with a median cost of just over $5000 per patient per year for drugs without orphan status.

Overall, nearly 15% of already approved orphan drugs subsequently add far more common diseases to their treatment repertoires.

Dr Makary and his colleagues recommend that, once a drug exceeds the basic tenets of the act—to treat fewer than 200,000 people—it should no longer receive government support or marketing exclusivity.

This can be achieved, the authors say, through pricing negotiations, clauses that reduce marketing exclusivity, and leveling of taxes once a medication becomes a blockbuster treatment for conditions not listed in the original FDA approval.

They say such measures would ensure the spirit of the original act is followed while continuing to provide critical economic incentives for truly rare diseases.

Lettuce

Photo by Daniel Ventura

Investigators have shown they can use lettuce to produce a factor IX product on a large scale.

The product successfully delivered factor IX to mice with hemophilia B while preventing the formation of inhibitors.

“This is a milestone in our field—to make a fully functional drug in plants, produce it at a large scale and in quantities sufficient for human clinical trials,” said Henry Daniell, PhD, of the University of Pennsylvania School of Dental Medicine in Philadelphia.

Dr Daniell and his colleagues described this work in Biomaterials.

This research builds on Dr Daniell’s previous work using genetically modified plants to introduce a protein into the body that would teach the immune system to tolerate clotting factors given as a treatment for hemophilia.

In that study, Dr Daniell and his colleagues successfully stopped and even reversed the production of inhibitors by feeding the plant-based drug to mice with hemophilia A. At that time, the investigators used a tobacco plant platform to “grow” the drug.

To take this approach to humans, Dr Daniell’s team turned to lettuce. They identified the genetic vector to introduce the therapeutic gene into the plant cells’ DNA and grow the drug within the lettuce leaves, which are then freeze-dried and encapsulated.

Two different growing systems were used. One was in Dr Daniell’s greenhouse, a high-tech facility that grows the plants in soil, using natural light.

The second system was used in the Fraunhofer USA facility, which more closely replicates how a commercial pharmaceutical production facility would run, using a hydroponic system and artificial lighting.

The investigators determined they could produce 36,000 doses in just 1000 square feet and harvest a new batch of pharmaceutical-containing lettuce every 4 to 6 weeks.

“This changes the way we think about delivering protein-based drugs and making them affordable to the global population,” Dr Daniell said.

“Over 90% of the global population can’t afford protein drugs, like insulin, due to the expense of production and the required refrigeration for storage or transportation. I am determined to challenge this scenario.”

Lettuce

Photo by Daniel Ventura

Investigators have shown they can use lettuce to produce a factor IX product on a large scale.

The product successfully delivered factor IX to mice with hemophilia B while preventing the formation of inhibitors.

“This is a milestone in our field—to make a fully functional drug in plants, produce it at a large scale and in quantities sufficient for human clinical trials,” said Henry Daniell, PhD, of the University of Pennsylvania School of Dental Medicine in Philadelphia.

Dr Daniell and his colleagues described this work in Biomaterials.

This research builds on Dr Daniell’s previous work using genetically modified plants to introduce a protein into the body that would teach the immune system to tolerate clotting factors given as a treatment for hemophilia.

In that study, Dr Daniell and his colleagues successfully stopped and even reversed the production of inhibitors by feeding the plant-based drug to mice with hemophilia A. At that time, the investigators used a tobacco plant platform to “grow” the drug.

To take this approach to humans, Dr Daniell’s team turned to lettuce. They identified the genetic vector to introduce the therapeutic gene into the plant cells’ DNA and grow the drug within the lettuce leaves, which are then freeze-dried and encapsulated.

Two different growing systems were used. One was in Dr Daniell’s greenhouse, a high-tech facility that grows the plants in soil, using natural light.

The second system was used in the Fraunhofer USA facility, which more closely replicates how a commercial pharmaceutical production facility would run, using a hydroponic system and artificial lighting.

The investigators determined they could produce 36,000 doses in just 1000 square feet and harvest a new batch of pharmaceutical-containing lettuce every 4 to 6 weeks.

“This changes the way we think about delivering protein-based drugs and making them affordable to the global population,” Dr Daniell said.

“Over 90% of the global population can’t afford protein drugs, like insulin, due to the expense of production and the required refrigeration for storage or transportation. I am determined to challenge this scenario.”

Lettuce

Photo by Daniel Ventura

Investigators have shown they can use lettuce to produce a factor IX product on a large scale.

The product successfully delivered factor IX to mice with hemophilia B while preventing the formation of inhibitors.

“This is a milestone in our field—to make a fully functional drug in plants, produce it at a large scale and in quantities sufficient for human clinical trials,” said Henry Daniell, PhD, of the University of Pennsylvania School of Dental Medicine in Philadelphia.

Dr Daniell and his colleagues described this work in Biomaterials.

This research builds on Dr Daniell’s previous work using genetically modified plants to introduce a protein into the body that would teach the immune system to tolerate clotting factors given as a treatment for hemophilia.

In that study, Dr Daniell and his colleagues successfully stopped and even reversed the production of inhibitors by feeding the plant-based drug to mice with hemophilia A. At that time, the investigators used a tobacco plant platform to “grow” the drug.

To take this approach to humans, Dr Daniell’s team turned to lettuce. They identified the genetic vector to introduce the therapeutic gene into the plant cells’ DNA and grow the drug within the lettuce leaves, which are then freeze-dried and encapsulated.

Two different growing systems were used. One was in Dr Daniell’s greenhouse, a high-tech facility that grows the plants in soil, using natural light.

The second system was used in the Fraunhofer USA facility, which more closely replicates how a commercial pharmaceutical production facility would run, using a hydroponic system and artificial lighting.

The investigators determined they could produce 36,000 doses in just 1000 square feet and harvest a new batch of pharmaceutical-containing lettuce every 4 to 6 weeks.

“This changes the way we think about delivering protein-based drugs and making them affordable to the global population,” Dr Daniell said.

“Over 90% of the global population can’t afford protein drugs, like insulin, due to the expense of production and the required refrigeration for storage or transportation. I am determined to challenge this scenario.”

Multiple myeloma

The US Food and Drug Administration (FDA) has approved ixazomib (Ninlaro), the first oral proteasome inhibitor, for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received at least 1 prior therapy.

The FDA previously granted ixazomib priority review and orphan designation.

The regulatory submission for ixazomib was primarily based on results from the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior progression-free survival when compared to patients who received placebo plus lenalidomide and dexamethasone.

Results from TOURMALINE-MM1 are scheduled to be presented at the 2015 ASH Annual Meeting (abstract 727) in December.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceuticals.

Multiple myeloma

The US Food and Drug Administration (FDA) has approved ixazomib (Ninlaro), the first oral proteasome inhibitor, for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received at least 1 prior therapy.

The FDA previously granted ixazomib priority review and orphan designation.

The regulatory submission for ixazomib was primarily based on results from the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior progression-free survival when compared to patients who received placebo plus lenalidomide and dexamethasone.

Results from TOURMALINE-MM1 are scheduled to be presented at the 2015 ASH Annual Meeting (abstract 727) in December.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceuticals.

Multiple myeloma

The US Food and Drug Administration (FDA) has approved ixazomib (Ninlaro), the first oral proteasome inhibitor, for use in combination with lenalidomide and dexamethasone to treat multiple myeloma (MM) patients who have received at least 1 prior therapy.

The FDA previously granted ixazomib priority review and orphan designation.

The regulatory submission for ixazomib was primarily based on results from the first interim analysis of the phase 3 TOURMALINE-MM1 trial.

In this trial, patients with relapsed and/or refractory MM who received ixazomib plus lenalidomide and dexamethasone had superior progression-free survival when compared to patients who received placebo plus lenalidomide and dexamethasone.

Results from TOURMALINE-MM1 are scheduled to be presented at the 2015 ASH Annual Meeting (abstract 727) in December.

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceuticals.