Pharmacy

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

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.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply 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 conditional marketing authorization application for blinatumomab is 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.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

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.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply 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 conditional marketing authorization application for blinatumomab is 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.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Micrograph showing ALL

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).

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.

The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.

The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply 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 conditional marketing authorization application for blinatumomab is 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.

Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab 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.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab 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.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.

Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).

Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.

The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.

The CHMP’s positive opinion was based on results with idarucizumab 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.

Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.

Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Micrograph showing CLL

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).

NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.

This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.

Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.

NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.

NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

Clinical effectiveness

The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.

For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.

Cost-effectiveness

Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.

Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.

Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.

The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).

Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Carfilzomib

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s positive opinion will be reviewed by the European Commission (EC).

The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.

ASPIRE trial

The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.

The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.

Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.

The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).

At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.

The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.

The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.

The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).

Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).

Carfilzomib development

Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.

Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.

Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.

Drug production

Photo courtesy of the FDA

Two newly published studies have raised concerns about the drug approval process in the US.

One study showed that, over the past two decades, the US Food and Drug Administration (FDA) has significantly increased its use of expedited development or review programs when approving new drugs.

Investigators said this increase cannot be attributed to an increase in the number of innovative new drug classes.

The other study revealed “wide variations” in evidence supporting the approval of supplemental drug applications.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted these studies and reported the results in The BMJ.

Authors of a related editorial wrote that these studies “give cause for concern about whether most new drugs are any more effective than existing products or whether their safety has been adequately assessed.”

Expedited approval

For the first study, the investigators looked at the FDA’s use of expedited development and review programs for drugs newly approved between 1987 and 2014. This included the orphan designation, fast track designation, priority review, and accelerated approval programs.

The FDA approved 774 drugs during the study period, and 33% of these were first-in-class agents. Priority review (43%) was the most-used program, followed by orphan designation (25%), fast track designation (19%), and accelerated approval (9%).

The investigators observed an increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved drug (P<0.001) and a 2.4% increase in the proportion of drugs associated with at least one of the programs (P=0.009).

The team noted that “this trend is being driven by drugs that are not first in class and thus potentially less innovative.”

They also said that, by the end of the study period, most newly approved drugs were associated with at least one of the programs. The peak was in 2005, when 75% (15/20) of newly approved drugs were associated with at least one program.

Supplemental approval

For the second study, Dr Kesselheim and his colleagues evaluated the quality of evidence underpinning FDA approval of supplemental drug applications (uses beyond a drug’s original indication) between 2005 and 2014.

The team assessed 295 supplemental drug approvals. They found a lack of trials using clinical outcome endpoints, a lack of trials including active comparators, and differences in the evidence according to types of approval.

Thirty percent of drug approvals for new indications were supported by trials with active comparators, as were 51% of modified-use approvals and 11% of approvals expanding the patient population (P<0.001).

Thirty-two percent of drug approvals for new indications were supported by trials using clinical outcome endpoints, as were 30% of modified-use approvals and 22% of expanded-population approvals (P=0.29).

The investigators said these findings “underscore the need for a robust system of post-approval drug monitoring for efficacy and safety, timely confirmatory studies, and re-examination of existing legislative incentives to promote the optimal delivery of evidence-based medicine.”

Drug production

Photo courtesy of the FDA

Two newly published studies have raised concerns about the drug approval process in the US.

One study showed that, over the past two decades, the US Food and Drug Administration (FDA) has significantly increased its use of expedited development or review programs when approving new drugs.

Investigators said this increase cannot be attributed to an increase in the number of innovative new drug classes.

The other study revealed “wide variations” in evidence supporting the approval of supplemental drug applications.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted these studies and reported the results in The BMJ.

Authors of a related editorial wrote that these studies “give cause for concern about whether most new drugs are any more effective than existing products or whether their safety has been adequately assessed.”

Expedited approval

For the first study, the investigators looked at the FDA’s use of expedited development and review programs for drugs newly approved between 1987 and 2014. This included the orphan designation, fast track designation, priority review, and accelerated approval programs.

The FDA approved 774 drugs during the study period, and 33% of these were first-in-class agents. Priority review (43%) was the most-used program, followed by orphan designation (25%), fast track designation (19%), and accelerated approval (9%).

The investigators observed an increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved drug (P<0.001) and a 2.4% increase in the proportion of drugs associated with at least one of the programs (P=0.009).

The team noted that “this trend is being driven by drugs that are not first in class and thus potentially less innovative.”

They also said that, by the end of the study period, most newly approved drugs were associated with at least one of the programs. The peak was in 2005, when 75% (15/20) of newly approved drugs were associated with at least one program.

Supplemental approval

For the second study, Dr Kesselheim and his colleagues evaluated the quality of evidence underpinning FDA approval of supplemental drug applications (uses beyond a drug’s original indication) between 2005 and 2014.

The team assessed 295 supplemental drug approvals. They found a lack of trials using clinical outcome endpoints, a lack of trials including active comparators, and differences in the evidence according to types of approval.

Thirty percent of drug approvals for new indications were supported by trials with active comparators, as were 51% of modified-use approvals and 11% of approvals expanding the patient population (P<0.001).

Thirty-two percent of drug approvals for new indications were supported by trials using clinical outcome endpoints, as were 30% of modified-use approvals and 22% of expanded-population approvals (P=0.29).

The investigators said these findings “underscore the need for a robust system of post-approval drug monitoring for efficacy and safety, timely confirmatory studies, and re-examination of existing legislative incentives to promote the optimal delivery of evidence-based medicine.”

Drug production

Photo courtesy of the FDA

Two newly published studies have raised concerns about the drug approval process in the US.

One study showed that, over the past two decades, the US Food and Drug Administration (FDA) has significantly increased its use of expedited development or review programs when approving new drugs.

Investigators said this increase cannot be attributed to an increase in the number of innovative new drug classes.

The other study revealed “wide variations” in evidence supporting the approval of supplemental drug applications.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues conducted these studies and reported the results in The BMJ.

Authors of a related editorial wrote that these studies “give cause for concern about whether most new drugs are any more effective than existing products or whether their safety has been adequately assessed.”

Expedited approval

For the first study, the investigators looked at the FDA’s use of expedited development and review programs for drugs newly approved between 1987 and 2014. This included the orphan designation, fast track designation, priority review, and accelerated approval programs.

The FDA approved 774 drugs during the study period, and 33% of these were first-in-class agents. Priority review (43%) was the most-used program, followed by orphan designation (25%), fast track designation (19%), and accelerated approval (9%).

The investigators observed an increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved drug (P<0.001) and a 2.4% increase in the proportion of drugs associated with at least one of the programs (P=0.009).

The team noted that “this trend is being driven by drugs that are not first in class and thus potentially less innovative.”

They also said that, by the end of the study period, most newly approved drugs were associated with at least one of the programs. The peak was in 2005, when 75% (15/20) of newly approved drugs were associated with at least one program.

Supplemental approval

For the second study, Dr Kesselheim and his colleagues evaluated the quality of evidence underpinning FDA approval of supplemental drug applications (uses beyond a drug’s original indication) between 2005 and 2014.

The team assessed 295 supplemental drug approvals. They found a lack of trials using clinical outcome endpoints, a lack of trials including active comparators, and differences in the evidence according to types of approval.

Thirty percent of drug approvals for new indications were supported by trials with active comparators, as were 51% of modified-use approvals and 11% of approvals expanding the patient population (P<0.001).

Thirty-two percent of drug approvals for new indications were supported by trials using clinical outcome endpoints, as were 30% of modified-use approvals and 22% of expanded-population approvals (P=0.29).

The investigators said these findings “underscore the need for a robust system of post-approval drug monitoring for efficacy and safety, timely confirmatory studies, and re-examination of existing legislative incentives to promote the optimal delivery of evidence-based medicine.”

Prescription medications

Photo courtesy of the CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation (NVAF).

The patients must have one or more risk factors for stroke, including congestive heart failure, hypertension, diabetes, prior stroke or transient ischemic attack, and age of 75 years or older.

In the UK, such patients are generally treated with warfarin or the newer oral anticoagulants dabigatran, rivaroxaban, and apixaban.

NICE decided that edoxaban should be added to that list because data suggest the drug is a clinically and cost-effective treatment option for these patients.

Edoxaban should be available on the National Health Service within 3 months of the date NICE’s final guidance was issued, September 23.

NICE’s guidance says the decision about whether to start treatment with edoxaban should be made after an informed discussion between the clinician and the patient about the risks and benefits of edoxaban compared with warfarin, apixaban, dabigatran, and rivaroxaban.

For patients considering switching from warfarin, edoxaban’s potential benefits should be weighed against its potential risks, taking into account the patient’s level of international normalized ratio control.

Clinical effectiveness

NICE’s conclusion that edoxaban is clinically effective was based primarily on results of the ENGAGE AF-TIMI 48 trial. In this trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

Results suggested edoxaban was at least non-inferior to warfarin with regard to efficacy, and edoxaban was associated with a significantly lower rate of major and fatal bleeding.

A committee advising NICE also reviewed a meta-analysis prepared by Daiichi Sankyo Co., Ltd., the company developing edoxaban.

The goal of the meta-analysis was to compare edoxaban with rivaroxaban, apixaban, and dabigatran. The analysis included 4 trials: ENGAGE AF-TIMI 48, ARISTOTLE (apixaban), RE-LY (dabigatran), and ROCKET-AF (rivaroxaban). All 4 trials had a warfarin comparator arm.

The results of the meta-analysis indicated that, for the composite endpoint of stroke and systemic embolism, efficacy was similar for high-dose edoxaban and the other new oral anticoagulants.

However, edoxaban significantly reduced major bleeding risk by 24% compared to rivaroxaban, 28% compared to dabigatran at 150 mg, and 17% compared to dabigatran at 110 mg. Major bleeding rates were similar for high-dose edoxaban and apixaban.

The committee advising NICE said these results should be interpreted with caution, but edoxaban is unlikely to be different from rivaroxaban, apixaban, and dabigatran in clinical practice.

Cost-effectiveness

Edoxaban costs £58.80 for a 28-tablet pack (60 mg or 30 mg), and the daily cost of treatment is £2.10 (excluding value-added tax). However, costs may vary in different settings because of negotiated procurement discounts.

The committee advising NICE analyzed cost information and concluded that edoxaban is cost-effective compared with warfarin, but there is insufficient evidence to distinguish between the clinical and cost-effectiveness of edoxaban and the other new oral anticoagulants.

Prescription medications

Photo courtesy of the CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation (NVAF).

The patients must have one or more risk factors for stroke, including congestive heart failure, hypertension, diabetes, prior stroke or transient ischemic attack, and age of 75 years or older.

In the UK, such patients are generally treated with warfarin or the newer oral anticoagulants dabigatran, rivaroxaban, and apixaban.

NICE decided that edoxaban should be added to that list because data suggest the drug is a clinically and cost-effective treatment option for these patients.

Edoxaban should be available on the National Health Service within 3 months of the date NICE’s final guidance was issued, September 23.

NICE’s guidance says the decision about whether to start treatment with edoxaban should be made after an informed discussion between the clinician and the patient about the risks and benefits of edoxaban compared with warfarin, apixaban, dabigatran, and rivaroxaban.

For patients considering switching from warfarin, edoxaban’s potential benefits should be weighed against its potential risks, taking into account the patient’s level of international normalized ratio control.

Clinical effectiveness

NICE’s conclusion that edoxaban is clinically effective was based primarily on results of the ENGAGE AF-TIMI 48 trial. In this trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

Results suggested edoxaban was at least non-inferior to warfarin with regard to efficacy, and edoxaban was associated with a significantly lower rate of major and fatal bleeding.

A committee advising NICE also reviewed a meta-analysis prepared by Daiichi Sankyo Co., Ltd., the company developing edoxaban.

The goal of the meta-analysis was to compare edoxaban with rivaroxaban, apixaban, and dabigatran. The analysis included 4 trials: ENGAGE AF-TIMI 48, ARISTOTLE (apixaban), RE-LY (dabigatran), and ROCKET-AF (rivaroxaban). All 4 trials had a warfarin comparator arm.

The results of the meta-analysis indicated that, for the composite endpoint of stroke and systemic embolism, efficacy was similar for high-dose edoxaban and the other new oral anticoagulants.

However, edoxaban significantly reduced major bleeding risk by 24% compared to rivaroxaban, 28% compared to dabigatran at 150 mg, and 17% compared to dabigatran at 110 mg. Major bleeding rates were similar for high-dose edoxaban and apixaban.

The committee advising NICE said these results should be interpreted with caution, but edoxaban is unlikely to be different from rivaroxaban, apixaban, and dabigatran in clinical practice.

Cost-effectiveness

Edoxaban costs £58.80 for a 28-tablet pack (60 mg or 30 mg), and the daily cost of treatment is £2.10 (excluding value-added tax). However, costs may vary in different settings because of negotiated procurement discounts.

The committee advising NICE analyzed cost information and concluded that edoxaban is cost-effective compared with warfarin, but there is insufficient evidence to distinguish between the clinical and cost-effectiveness of edoxaban and the other new oral anticoagulants.

Prescription medications

Photo courtesy of the CDC

The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the oral anticoagulant edoxaban tosylate (Lixiana) as an option for preventing stroke and systemic embolism in adults with non-valvular atrial fibrillation (NVAF).

The patients must have one or more risk factors for stroke, including congestive heart failure, hypertension, diabetes, prior stroke or transient ischemic attack, and age of 75 years or older.

In the UK, such patients are generally treated with warfarin or the newer oral anticoagulants dabigatran, rivaroxaban, and apixaban.

NICE decided that edoxaban should be added to that list because data suggest the drug is a clinically and cost-effective treatment option for these patients.

Edoxaban should be available on the National Health Service within 3 months of the date NICE’s final guidance was issued, September 23.

NICE’s guidance says the decision about whether to start treatment with edoxaban should be made after an informed discussion between the clinician and the patient about the risks and benefits of edoxaban compared with warfarin, apixaban, dabigatran, and rivaroxaban.

For patients considering switching from warfarin, edoxaban’s potential benefits should be weighed against its potential risks, taking into account the patient’s level of international normalized ratio control.

Clinical effectiveness

NICE’s conclusion that edoxaban is clinically effective was based primarily on results of the ENGAGE AF-TIMI 48 trial. In this trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

Results suggested edoxaban was at least non-inferior to warfarin with regard to efficacy, and edoxaban was associated with a significantly lower rate of major and fatal bleeding.

A committee advising NICE also reviewed a meta-analysis prepared by Daiichi Sankyo Co., Ltd., the company developing edoxaban.

The goal of the meta-analysis was to compare edoxaban with rivaroxaban, apixaban, and dabigatran. The analysis included 4 trials: ENGAGE AF-TIMI 48, ARISTOTLE (apixaban), RE-LY (dabigatran), and ROCKET-AF (rivaroxaban). All 4 trials had a warfarin comparator arm.

The results of the meta-analysis indicated that, for the composite endpoint of stroke and systemic embolism, efficacy was similar for high-dose edoxaban and the other new oral anticoagulants.

However, edoxaban significantly reduced major bleeding risk by 24% compared to rivaroxaban, 28% compared to dabigatran at 150 mg, and 17% compared to dabigatran at 110 mg. Major bleeding rates were similar for high-dose edoxaban and apixaban.

The committee advising NICE said these results should be interpreted with caution, but edoxaban is unlikely to be different from rivaroxaban, apixaban, and dabigatran in clinical practice.

Cost-effectiveness

Edoxaban costs £58.80 for a 28-tablet pack (60 mg or 30 mg), and the daily cost of treatment is £2.10 (excluding value-added tax). However, costs may vary in different settings because of negotiated procurement discounts.

The committee advising NICE analyzed cost information and concluded that edoxaban is cost-effective compared with warfarin, but there is insufficient evidence to distinguish between the clinical and cost-effectiveness of edoxaban and the other new oral anticoagulants.

Monoclonal antibodies

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted priority review for an application for ofatumumab (Arzerra) as maintenance therapy in

patients with relapsed chronic lymphocytic leukemia (CLL).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

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

The mAb is already FDA-approved to treat patients with CLL that is refractory to fludarabine and alemtuzumab. Ofatumumab is also approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

The FDA said it aims to complete its review of the application for ofatumumab as maintenance therapy in relapsed CLL by January 21, 2016.

PROLONG trial

The application for ofatumumab as maintenance is based on interim results from the phase 3 PROLONG (OMB112517) trial, which were presented at ASH 2014.

In this trial, researchers compared ofatumumab maintenance to no further treatment in patients with a complete or partial response after second-

or third-line treatment for CLL.

Interim results suggested that ofatumumab significantly improves progression-free survival but not overall survival.

The median progression-free survival was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive

maintenance (P<0.0001).

There was no significant difference in the median overall survival, which was not reached in either treatment arm.

Ofatumumab development

Ofatumumab is approved in more than 50 countries worldwide as monotherapy for CLL patients who are refractory to fludarabine and alemtuzumab.

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

Ofatumumab is not approved anywhere in the world as maintenance therapy for relapsed CLL. The drug is being developed by Genmab and Novartis.

Monoclonal antibodies

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted priority review for an application for ofatumumab (Arzerra) as maintenance therapy in

patients with relapsed chronic lymphocytic leukemia (CLL).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

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

The mAb is already FDA-approved to treat patients with CLL that is refractory to fludarabine and alemtuzumab. Ofatumumab is also approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

The FDA said it aims to complete its review of the application for ofatumumab as maintenance therapy in relapsed CLL by January 21, 2016.

PROLONG trial

The application for ofatumumab as maintenance is based on interim results from the phase 3 PROLONG (OMB112517) trial, which were presented at ASH 2014.

In this trial, researchers compared ofatumumab maintenance to no further treatment in patients with a complete or partial response after second-

or third-line treatment for CLL.

Interim results suggested that ofatumumab significantly improves progression-free survival but not overall survival.

The median progression-free survival was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive

maintenance (P<0.0001).

There was no significant difference in the median overall survival, which was not reached in either treatment arm.

Ofatumumab development

Ofatumumab is approved in more than 50 countries worldwide as monotherapy for CLL patients who are refractory to fludarabine and alemtuzumab.

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

Ofatumumab is not approved anywhere in the world as maintenance therapy for relapsed CLL. The drug is being developed by Genmab and Novartis.

Monoclonal antibodies

Photo by Linda Bartlett

The US Food and Drug Administration (FDA) has granted priority review for an application for ofatumumab (Arzerra) as maintenance therapy in

patients with relapsed chronic lymphocytic leukemia (CLL).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

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

The mAb is already FDA-approved to treat patients with CLL that is refractory to fludarabine and alemtuzumab. Ofatumumab is also approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

The FDA said it aims to complete its review of the application for ofatumumab as maintenance therapy in relapsed CLL by January 21, 2016.

PROLONG trial

The application for ofatumumab as maintenance is based on interim results from the phase 3 PROLONG (OMB112517) trial, which were presented at ASH 2014.

In this trial, researchers compared ofatumumab maintenance to no further treatment in patients with a complete or partial response after second-

or third-line treatment for CLL.

Interim results suggested that ofatumumab significantly improves progression-free survival but not overall survival.

The median progression-free survival was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive

maintenance (P<0.0001).

There was no significant difference in the median overall survival, which was not reached in either treatment arm.

Ofatumumab development

Ofatumumab is approved in more than 50 countries worldwide as monotherapy for CLL patients who are refractory to fludarabine and alemtuzumab.

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

Ofatumumab is not approved anywhere in the world as maintenance therapy for relapsed CLL. The drug is being developed by Genmab and Novartis.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to a gene therapy product being developed to treat hemophilia B.

The product, DTX101, is designed to deliver factor IX gene expression in a durable fashion to prevent the long-term complications of hemophilia B.

Preclinical studies have indicated that DTX101 has the potential to be a well-tolerated, effective therapy for hemophilia B, according to Dimension Therapeutics, Inc., the company developing DTX101.

The company said it expects to initiate a multicenter, phase 1/2 study to evaluate DTX101 in adults with moderate/severe to severe hemophilia B by the end of this year.

DTX101 also has orphan designation from the FDA.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to a gene therapy product being developed to treat hemophilia B.

The product, DTX101, is designed to deliver factor IX gene expression in a durable fashion to prevent the long-term complications of hemophilia B.

Preclinical studies have indicated that DTX101 has the potential to be a well-tolerated, effective therapy for hemophilia B, according to Dimension Therapeutics, Inc., the company developing DTX101.

The company said it expects to initiate a multicenter, phase 1/2 study to evaluate DTX101 in adults with moderate/severe to severe hemophilia B by the end of this year.

DTX101 also has orphan designation from the FDA.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to a gene therapy product being developed to treat hemophilia B.

The product, DTX101, is designed to deliver factor IX gene expression in a durable fashion to prevent the long-term complications of hemophilia B.

Preclinical studies have indicated that DTX101 has the potential to be a well-tolerated, effective therapy for hemophilia B, according to Dimension Therapeutics, Inc., the company developing DTX101.

The company said it expects to initiate a multicenter, phase 1/2 study to evaluate DTX101 in adults with moderate/severe to severe hemophilia B by the end of this year.

DTX101 also has orphan designation from the FDA.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of 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 PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

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.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of 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 PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

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.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Micrograph showing

multiple myeloma

The US Food and Drug Administration (FDA) has granted priority review for 4 drugs intended to treat multiple myeloma (MM): elotuzumab (Empliciti), daratumumab, ixazomib (MLN9708), and carfilzomib (Kyprolis).

The FDA grants priority review to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention, or diagnosis of a serious condition.

The designation shortens the review period from 10 months to 6 months.

Carfilzomib

Carfilzomib, an injectable proteasome inhibitor, is currently under review for use in combination with dexamethasone to treat patients with relapsed MM who have received at least 1 prior therapy.

Carfilzomib is already FDA-approved for use in combination with lenalidomide and dexamethasone to treat patients with relapsed MM who have received 1 to 3 prior lines of therapy.

Carfilzomib also has accelerated approval from the FDA as monotherapy for MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completing their last treatment.

The new regulatory submission for carfilzomib is based on data from the phase 3 ENDEAVOR trial, which were presented at ASCO 2015. In this trial, relapsed MM patients who received carfilzomib and low-dose dexamethasone had significantly longer progression-free survival (PFS) than patients who received bortezomib and low-dose dexamethasone.

Carfilzomib is under development by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Ixazomib

Ixazomib, an oral proteasome inhibitor, is under review for the treatment of relapsed and/or refractory MM. Ixazomib has orphan drug designation from the FDA for this patient population.

The regulatory submission for ixazomib is primarily based on results of 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 PFS to patients who received placebo plus lenalidomide and dexamethasone, according to Takeda Pharmaceutical Company Limited, the company developing ixazomib. Detailed data from this study have not yet been released.

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.

Daratumumab

Daratumumab, an investigational human anti-CD38 monoclonal antibody, is under review as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an IMiD, or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an IMiD.

Daratumumab already has fast track, breakthrough therapy, and orphan drug designations from the FDA.

The regulatory submission for daratumumab is primarily supported by data from the phase 2 MMY2002 (SIRIUS) monotherapy study, which were presented at ASCO 2015. Results from this study indicated that daratumumab can produce responses in heavily pretreated MM patients.

Additional data from 4 other studies, including the phase 1/2 GEN501 monotherapy study, which was recently published in NEJM, also support the submission.

Daratumumab is under development by Janssen Research & Development, LLC.

Elotuzumab

Elotuzumab, a signaling lymphocyte activation molecule (SLAMF7)-directed immunostimulatory antibody, is under review for use in combination with lenalidomide and dexamethasone to treat MM patients who have received at least 1 prior treatment.

The FDA has already granted elotuzumab breakthrough therapy and orphan drug designations.

The regulatory submission for elotuzumab is primarily supported by data from the ELOQUENT-2 trial, which were presented at ASCO 2015. In this phase 3 study, researchers evaluated elotuzumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone.

The submission is also supported by data from the CA204-009 trial, which were presented at EHA 2015. In this phase 2 study, researchers evaluated elotuzumab in combination with bortezomib and dexamethasone compared to bortezomib and dexamethasone alone.

Results from both trials suggested that adding elotuzumab to combination treatment can prolong PFS in MM patients.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.

Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.

Photo by Octapharma

The US Food and Drug Administration (FDA) has approved the recombinant factor VIII product simoctocog alfa (Nuwiq) for adults and children with hemophilia A.

The approval includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.

Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.

Simoctocog alfa is already approved for use in the European Union, Argentina, Australia, and Canada.

In the US, simoctocog alfa is being developed by Octapharma USA, a subsidiary of Octapharma AG.

According to Octapharma USA, simoctocog alfa should be available in the US by early 2016. The company plans to offer hemophilia A patients educational and support services in connection with the product.

Trials of simoctocog alfa

Simoctocog alfa has been evaluated for safety in 5 prospective trials and for efficacy in 3 prospective studies.

A total of 135 previously treated patients with severe hemophilia A have received simoctocog alfa across all the studies. This includes 74 adults, 3 adolescents between ages 12 and 17, and 58 pediatric patients between ages 2 and 11.

The patients were treated with a total of 16,134 infusions over 15,950 exposure days.

In a study of adults, the overall prophylactic efficacy of simoctocog alfa for spontaneous bleeds was rated “excellent” or “good” in 92% of patients. In a study of children, prophylactic efficacy for spontaneous bleeds was rated “excellent” or “good” in 97% of patients.

The mean annualized bleeding rates for spontaneous bleeds during prophylaxis were approximately 1.5 in children and 1.2 in adults.

For hemophilia A patients receiving simoctocog alfa prophylaxis compared to on-demand treatment, the annualized bleeding rates were reduced 96% for adults and 93% for children.

Treatment of breakthrough bleeds during simoctocog alfa prophylaxis was rated as “excellent” or “good” in 100% of bleeds (30/30) in adults and 82% of bleeds (89/108) in children.

For on-demand treatment with simoctocog alfa in 20 adults and 2 adolescents, efficacy for the treatment of bleeds was considered “excellent” or “good” in 94% of bleeds (931/986).

The overall efficacy in surgical prophylaxis was rated “excellent” or “good” in 97% of procedures using simoctocog alfa (32/33).

For all the trials of simoctocog alfa, there were 7 adverse events reported. Each of these events occurred once, with a rate of 0.7% across all 135 patients. The events were paresthesia, headache, injection site inflammation, injection site pain, back pain, vertigo, and dry mouth.

Non-neutralizing anti-factor VIII antibodies (without inhibitory activity as measured by the modified Bethesda assay) were reported in 4 patients (3%). Three of the 4 patients had pre-existing non-neutralizing antibodies prior to simoctocog alfa exposure.

For more details on simoctocog alfa, see the full prescribing information, available at www.octapharmausa.com.