Pharmacy

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 biosimilars of the low-molecular-weight heparin enoxaparin.

Both of the agents, Inhixa and Thorinane, are intended to prevent and treat thrombosis-related disorders in adults.

The CHMP’s recommendations will be reviewed by the European Commission.

If the recommendations are formally adopted, Inhixa and Thorinane will be approved for use in the European Union as well as Norway, Liechtenstein, and Iceland.

Both Inhixa and Thorinane are indicated for:

• Prophylaxis of venous thromboembolism (VTE), particularly in patients undergoing orthopedic, general, or oncological surgery.
• VTE prophylaxis in patients bedridden due to acute illnesses, including acute heart failure, acute respiratory failure, severe infections, and exacerbation of rheumatic diseases causing immobilization of the patient (applies to strengths of 40 mg/0.4 mL).
• Treatment of deep vein thrombosis, complicated or uncomplicated by pulmonary embolism.
• Treatment of unstable angina and non-Q wave myocardial infarction, in combination with acetylsalicylic acid.
• Treatment of acute ST segment elevation myocardial infarction, including patients who will be treated conservatively or who will later undergo percutaneous coronary angioplasty (applies to strengths of 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1 mL).
• VTE prevention in the extracorporeal circulation during hemodialysis.

If approved, Inhixa will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

And Thorinane will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

Inhixa is being developed by Techdow Europe AB, and Thorinane is being developed by Pharmathen S.A.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 biosimilars of the low-molecular-weight heparin enoxaparin.

Both of the agents, Inhixa and Thorinane, are intended to prevent and treat thrombosis-related disorders in adults.

The CHMP’s recommendations will be reviewed by the European Commission.

If the recommendations are formally adopted, Inhixa and Thorinane will be approved for use in the European Union as well as Norway, Liechtenstein, and Iceland.

Both Inhixa and Thorinane are indicated for:

• Prophylaxis of venous thromboembolism (VTE), particularly in patients undergoing orthopedic, general, or oncological surgery.
• VTE prophylaxis in patients bedridden due to acute illnesses, including acute heart failure, acute respiratory failure, severe infections, and exacerbation of rheumatic diseases causing immobilization of the patient (applies to strengths of 40 mg/0.4 mL).
• Treatment of deep vein thrombosis, complicated or uncomplicated by pulmonary embolism.
• Treatment of unstable angina and non-Q wave myocardial infarction, in combination with acetylsalicylic acid.
• Treatment of acute ST segment elevation myocardial infarction, including patients who will be treated conservatively or who will later undergo percutaneous coronary angioplasty (applies to strengths of 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1 mL).
• VTE prevention in the extracorporeal circulation during hemodialysis.

If approved, Inhixa will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

And Thorinane will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

Inhixa is being developed by Techdow Europe AB, and Thorinane is being developed by Pharmathen S.A.

Thrombus

Image by Andre E.X. Brown

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for 2 biosimilars of the low-molecular-weight heparin enoxaparin.

Both of the agents, Inhixa and Thorinane, are intended to prevent and treat thrombosis-related disorders in adults.

The CHMP’s recommendations will be reviewed by the European Commission.

If the recommendations are formally adopted, Inhixa and Thorinane will be approved for use in the European Union as well as Norway, Liechtenstein, and Iceland.

Both Inhixa and Thorinane are indicated for:

• Prophylaxis of venous thromboembolism (VTE), particularly in patients undergoing orthopedic, general, or oncological surgery.
• VTE prophylaxis in patients bedridden due to acute illnesses, including acute heart failure, acute respiratory failure, severe infections, and exacerbation of rheumatic diseases causing immobilization of the patient (applies to strengths of 40 mg/0.4 mL).
• Treatment of deep vein thrombosis, complicated or uncomplicated by pulmonary embolism.
• Treatment of unstable angina and non-Q wave myocardial infarction, in combination with acetylsalicylic acid.
• Treatment of acute ST segment elevation myocardial infarction, including patients who will be treated conservatively or who will later undergo percutaneous coronary angioplasty (applies to strengths of 60 mg/0.6 mL, 80 mg/0.8 mL, and 100 mg/1 mL).
• VTE prevention in the extracorporeal circulation during hemodialysis.

If approved, Inhixa will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

And Thorinane will be available as a solution for injection—2000 IU (20 mg) in 0.2 mL, 4000 IU (40 mg) in 0.4 mL, 6000 IU (60 mg) in 0.6 mL, 8000 IU (80 mg) in 0.8 mL, and 10,000 IU (100 mg) in 1 mL.

Inhixa is being developed by Techdow Europe AB, and Thorinane is being developed by Pharmathen S.A.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

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

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

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

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

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

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

Ibrutinib (Imbruvica)

Photo courtesy of Janssen

Health Canada has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) as a first-line treatment for patients with active chronic lymphocytic leukemia (CLL).

This is the fourth approval for ibrutinib in Canada. The drug is now approved for use in all CLL patients, patients with Waldenström’s macroglobulinemia, and patients with relapsed or refractory mantle cell lymphoma (conditional approval).

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

The latest approval of ibrutinib is based on results from the phase 3 RESONATE-2 trial

(PCYC-1115), which were presented at the 2015 ASH Annual Meeting and

simultaneously published in NEJM.

RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.

Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.

Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.

Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.

Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).

Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five

patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.

The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.

The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).

Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).

White blood cells

The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.

The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.

Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.

Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.

Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
• To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

White blood cells

The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.

The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.

Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.

Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.

Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
• To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

White blood cells

The US Food and Drug Administration (FDA) has decided not to approve Novartis’s application for a biosimilar of Amgen’s Neulasta, also known by the generic name pegfilgrastim.

The FDA issued a complete response letter for the pegfilgrastim biosimilar last month.

Novartis has not provided details about the agency’s decision or the contents of the letter, but the company said it is working with the FDA to answer its questions about the drug.

Novartis was seeking approval for its pegfilgrastim biosimilar for the same indication as Amgen’s Neulasta.

Neulasta is a leukocyte growth factor that is FDA-approved for the following indications:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
• To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Neulasta is not FDA-approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Lenalidomide (Revlimid)
Photo courtesy of Celgene

The European Commission (EC) has approved lenalidomide (Revlimid®) for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL).

The EC previously approved lenalidomide as a single agent to treat adults with newly diagnosed multiple myeloma who are not eligible for transplant and in combination with dexamethasone to treat adults with multiple myeloma who have received at least 1 prior therapy.

The EC also approved lenalidomide for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

Lenalidomide is a product of Celgene Corporation.

The EC’s decision to approve lenalidomide for MCL was based on data from a phase 2 trial known as SPRINT or MCL-002. The study included 254 MCL patients who were refractory to their last treatment or had relapsed 1 to 3 times.

The patients were randomized (2:1) to receive lenalidomide (n=170) or a single-agent therapy of the investigator’s choice (n=84), which included rituximab, gemcitabine, fludarabine, chlorambucil, and cytarabine. Patients who progressed on investigator’s choice could cross over to the lenalidomide arm.

At a median follow-up of 15.9 months, the overall response rate was 40% in the lenalidomide arm and 11% in the investigator’s choice arm (P<0.001).

The complete response rates were 5% and 0%, respectively (P=0.04). The median duration of response was 16 months and 10.4 months, respectively.

Lenalidomide significantly prolonged progression-free survival. The median was 8.7 months in the lenalidomide arm and 5.2 months in the investigator’s choice arm (P=0.004).

However, there was no significant difference in overall survival between the treatment arms. The median was 27.8 months in the lenalidomide arm and 21.2 months in the investigator’s choice arm (P=0.45).

The incidence of treatment-related adverse events was 84% in the lenalidomide arm and 60% in the investigator’s choice arm.

Common adverse events that occurred more frequently in the lenalidomide arm than the investigator’s choice arm were neutropenia (51%), anemia (29%), diarrhea (23%), fatigue (21%), constipation (17%), pyrexia (17%), and rash (16%).

Lenalidomide (Revlimid)
Photo courtesy of Celgene

The European Commission (EC) has approved lenalidomide (Revlimid®) for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL).

The EC previously approved lenalidomide as a single agent to treat adults with newly diagnosed multiple myeloma who are not eligible for transplant and in combination with dexamethasone to treat adults with multiple myeloma who have received at least 1 prior therapy.

The EC also approved lenalidomide for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

Lenalidomide is a product of Celgene Corporation.

The EC’s decision to approve lenalidomide for MCL was based on data from a phase 2 trial known as SPRINT or MCL-002. The study included 254 MCL patients who were refractory to their last treatment or had relapsed 1 to 3 times.

The patients were randomized (2:1) to receive lenalidomide (n=170) or a single-agent therapy of the investigator’s choice (n=84), which included rituximab, gemcitabine, fludarabine, chlorambucil, and cytarabine. Patients who progressed on investigator’s choice could cross over to the lenalidomide arm.

At a median follow-up of 15.9 months, the overall response rate was 40% in the lenalidomide arm and 11% in the investigator’s choice arm (P<0.001).

The complete response rates were 5% and 0%, respectively (P=0.04). The median duration of response was 16 months and 10.4 months, respectively.

Lenalidomide significantly prolonged progression-free survival. The median was 8.7 months in the lenalidomide arm and 5.2 months in the investigator’s choice arm (P=0.004).

However, there was no significant difference in overall survival between the treatment arms. The median was 27.8 months in the lenalidomide arm and 21.2 months in the investigator’s choice arm (P=0.45).

The incidence of treatment-related adverse events was 84% in the lenalidomide arm and 60% in the investigator’s choice arm.

Common adverse events that occurred more frequently in the lenalidomide arm than the investigator’s choice arm were neutropenia (51%), anemia (29%), diarrhea (23%), fatigue (21%), constipation (17%), pyrexia (17%), and rash (16%).

Lenalidomide (Revlimid)
Photo courtesy of Celgene

The European Commission (EC) has approved lenalidomide (Revlimid®) for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL).

The EC previously approved lenalidomide as a single agent to treat adults with newly diagnosed multiple myeloma who are not eligible for transplant and in combination with dexamethasone to treat adults with multiple myeloma who have received at least 1 prior therapy.

The EC also approved lenalidomide for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

Lenalidomide is a product of Celgene Corporation.

The EC’s decision to approve lenalidomide for MCL was based on data from a phase 2 trial known as SPRINT or MCL-002. The study included 254 MCL patients who were refractory to their last treatment or had relapsed 1 to 3 times.

The patients were randomized (2:1) to receive lenalidomide (n=170) or a single-agent therapy of the investigator’s choice (n=84), which included rituximab, gemcitabine, fludarabine, chlorambucil, and cytarabine. Patients who progressed on investigator’s choice could cross over to the lenalidomide arm.

At a median follow-up of 15.9 months, the overall response rate was 40% in the lenalidomide arm and 11% in the investigator’s choice arm (P<0.001).

The complete response rates were 5% and 0%, respectively (P=0.04). The median duration of response was 16 months and 10.4 months, respectively.

Lenalidomide significantly prolonged progression-free survival. The median was 8.7 months in the lenalidomide arm and 5.2 months in the investigator’s choice arm (P=0.004).

However, there was no significant difference in overall survival between the treatment arms. The median was 27.8 months in the lenalidomide arm and 21.2 months in the investigator’s choice arm (P=0.45).

The incidence of treatment-related adverse events was 84% in the lenalidomide arm and 60% in the investigator’s choice arm.

Common adverse events that occurred more frequently in the lenalidomide arm than the investigator’s choice arm were neutropenia (51%), anemia (29%), diarrhea (23%), fatigue (21%), constipation (17%), pyrexia (17%), and rash (16%).

T cells

Image from NIAID

The US Food and Drug Administration (FDA) has removed the clinical hold on the phase 2 ROCKET trial, a study of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The trial will continue with a revised protocol, under which patients will receive only cyclophosphamide as conditioning.

The ROCKET trial was placed on hold after 3 patients died of cerebral edema.

Juno Therapeutics, the company developing JCAR015, believes the deaths were likely a result of adding fludarabine to the conditioning regimen.

Patients initially received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy. Adding fludarabine to conditioning had been shown to increase the efficacy of 2 other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials.

However, in the ROCKET trial, the addition of fludarabine was associated with an increase in the incidence of severe neurotoxicity and the 3 deaths from cerebral edema.

Although other factors may have contributed to the deaths, Juno said fludarabine was the most likely culprit. So the company asked the FDA if it could continue the ROCKET trial using conditioning with cyclophosphamide alone.

In response, the FDA requested that Juno submit a revised patient informed consent form, revised investigator brochure, revised trial protocol, and a copy of a presentation the company made to the FDA.

The FDA said it would review these documents within 30 days of receiving them, but the review only took a few days. The agency agreed to lift the clinical hold and allow the trial to proceed with the revised protocol.

ROCKET is not the first trial of JCAR015 to be placed on clinical hold. The phase 1 trial of the therapy was placed on hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells

Image from NIAID

The US Food and Drug Administration (FDA) has removed the clinical hold on the phase 2 ROCKET trial, a study of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The trial will continue with a revised protocol, under which patients will receive only cyclophosphamide as conditioning.

The ROCKET trial was placed on hold after 3 patients died of cerebral edema.

Juno Therapeutics, the company developing JCAR015, believes the deaths were likely a result of adding fludarabine to the conditioning regimen.

Patients initially received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy. Adding fludarabine to conditioning had been shown to increase the efficacy of 2 other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials.

However, in the ROCKET trial, the addition of fludarabine was associated with an increase in the incidence of severe neurotoxicity and the 3 deaths from cerebral edema.

Although other factors may have contributed to the deaths, Juno said fludarabine was the most likely culprit. So the company asked the FDA if it could continue the ROCKET trial using conditioning with cyclophosphamide alone.

In response, the FDA requested that Juno submit a revised patient informed consent form, revised investigator brochure, revised trial protocol, and a copy of a presentation the company made to the FDA.

The FDA said it would review these documents within 30 days of receiving them, but the review only took a few days. The agency agreed to lift the clinical hold and allow the trial to proceed with the revised protocol.

ROCKET is not the first trial of JCAR015 to be placed on clinical hold. The phase 1 trial of the therapy was placed on hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells

Image from NIAID

The US Food and Drug Administration (FDA) has removed the clinical hold on the phase 2 ROCKET trial, a study of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The trial will continue with a revised protocol, under which patients will receive only cyclophosphamide as conditioning.

The ROCKET trial was placed on hold after 3 patients died of cerebral edema.

Juno Therapeutics, the company developing JCAR015, believes the deaths were likely a result of adding fludarabine to the conditioning regimen.

Patients initially received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy. Adding fludarabine to conditioning had been shown to increase the efficacy of 2 other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials.

However, in the ROCKET trial, the addition of fludarabine was associated with an increase in the incidence of severe neurotoxicity and the 3 deaths from cerebral edema.

Although other factors may have contributed to the deaths, Juno said fludarabine was the most likely culprit. So the company asked the FDA if it could continue the ROCKET trial using conditioning with cyclophosphamide alone.

In response, the FDA requested that Juno submit a revised patient informed consent form, revised investigator brochure, revised trial protocol, and a copy of a presentation the company made to the FDA.

The FDA said it would review these documents within 30 days of receiving them, but the review only took a few days. The agency agreed to lift the clinical hold and allow the trial to proceed with the revised protocol.

ROCKET is not the first trial of JCAR015 to be placed on clinical hold. The phase 1 trial of the therapy was placed on hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

Red blood cells

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan designation for Coversin for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and the drug can achieve full complement inhibition in the blood of PNH patients who are resistant to the drug eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is administering the drug to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. And the only drug-related adverse event has been occasional local and transient irritation at the injection site.

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

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

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

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

Red blood cells

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan designation for Coversin for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and the drug can achieve full complement inhibition in the blood of PNH patients who are resistant to the drug eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is administering the drug to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. And the only drug-related adverse event has been occasional local and transient irritation at the injection site.

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

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

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

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

Red blood cells

The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan designation for Coversin for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a second-generation complement inhibitor that acts on complement component-C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and the drug can achieve full complement inhibition in the blood of PNH patients who are resistant to the drug eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is administering the drug to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. And the only drug-related adverse event has been occasional local and transient irritation at the injection site.

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

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

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

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

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.