User login
The European Medicines Agency (EMA) has concluded there is “no clear and consistent evidence” of a difference in inhibitor development between the 2 classes of factor VIII (FVIII) products.
A review of data from several studies has suggested that hemophilia A patients are no more likely to develop inhibitors if they receive a recombinant FVIII product rather than a plasma-derived FVIII product.
The review began after publication of the SIPPET study1, which suggested that patients who received plasma-derived FVIII had a lower incidence of inhibitors than patients treated with recombinant FVIII.
To test this conclusion, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) reviewed data on all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation FVIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The PRAC examined data from the SIPPET study and additional clinical trials and observational studies.2-5
The data did not show any statistically significant or clinically meaningful difference in inhibitor risk between FVIII classes.
The PRAC said results of the SIPPET study cannot be extrapolated to individual products, as the study only included a small number of FVIII products.
The PRAC’s conclusion was sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for adoption of the EMA’s final opinion. And the CHMP has adopted the opinion that there is “no clear and consistent evidence” of a difference in inhibitor development.
The CHMP’s opinion will be forwarded to the European Commission, which will issue a final, legally binding decision applicable in all European Union member states. The European Commission typically adheres to the CHMP’s recommendations.
The EMA said prescribing information for FVIII products will be updated as appropriate to add inhibitor development as a very common side effect in previously untreated patients and as uncommon in previously treated patients.
The warning on inhibitor development will be amended to state that low titers of inhibitors pose less risk of insufficient response than high titers. 
1. Peyvandi F, Mannucci PM, Garagiola I et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med (2016), 374:2054-64.
2. Gouw SC et al. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood (2007), 109:4648-54.
3. Gouw SC et al. PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med (2013), 368:231-9.
4. Iorio A et al. Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series. Haemophilia (2017), 23:255-63.
5. Fischer K et al. Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project. Thromb Haemost (2015) 113:968-75.
The European Medicines Agency (EMA) has concluded there is “no clear and consistent evidence” of a difference in inhibitor development between the 2 classes of factor VIII (FVIII) products.
A review of data from several studies has suggested that hemophilia A patients are no more likely to develop inhibitors if they receive a recombinant FVIII product rather than a plasma-derived FVIII product.
The review began after publication of the SIPPET study1, which suggested that patients who received plasma-derived FVIII had a lower incidence of inhibitors than patients treated with recombinant FVIII.
To test this conclusion, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) reviewed data on all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation FVIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The PRAC examined data from the SIPPET study and additional clinical trials and observational studies.2-5
The data did not show any statistically significant or clinically meaningful difference in inhibitor risk between FVIII classes.
The PRAC said results of the SIPPET study cannot be extrapolated to individual products, as the study only included a small number of FVIII products.
The PRAC’s conclusion was sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for adoption of the EMA’s final opinion. And the CHMP has adopted the opinion that there is “no clear and consistent evidence” of a difference in inhibitor development.
The CHMP’s opinion will be forwarded to the European Commission, which will issue a final, legally binding decision applicable in all European Union member states. The European Commission typically adheres to the CHMP’s recommendations.
The EMA said prescribing information for FVIII products will be updated as appropriate to add inhibitor development as a very common side effect in previously untreated patients and as uncommon in previously treated patients.
The warning on inhibitor development will be amended to state that low titers of inhibitors pose less risk of insufficient response than high titers.
1. Peyvandi F, Mannucci PM, Garagiola I et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med (2016), 374:2054-64.
2. Gouw SC et al. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood (2007), 109:4648-54.
3. Gouw SC et al. PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med (2013), 368:231-9.
4. Iorio A et al. Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series. Haemophilia (2017), 23:255-63.
5. Fischer K et al. Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project. Thromb Haemost (2015) 113:968-75.
The European Medicines Agency (EMA) has concluded there is “no clear and consistent evidence” of a difference in inhibitor development between the 2 classes of factor VIII (FVIII) products.
A review of data from several studies has suggested that hemophilia A patients are no more likely to develop inhibitors if they receive a recombinant FVIII product rather than a plasma-derived FVIII product.
The review began after publication of the SIPPET study1, which suggested that patients who received plasma-derived FVIII had a lower incidence of inhibitors than patients treated with recombinant FVIII.
To test this conclusion, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) reviewed data on all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation FVIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The PRAC examined data from the SIPPET study and additional clinical trials and observational studies.2-5
The data did not show any statistically significant or clinically meaningful difference in inhibitor risk between FVIII classes.
The PRAC said results of the SIPPET study cannot be extrapolated to individual products, as the study only included a small number of FVIII products.
The PRAC’s conclusion was sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for adoption of the EMA’s final opinion. And the CHMP has adopted the opinion that there is “no clear and consistent evidence” of a difference in inhibitor development.
The CHMP’s opinion will be forwarded to the European Commission, which will issue a final, legally binding decision applicable in all European Union member states. The European Commission typically adheres to the CHMP’s recommendations.
The EMA said prescribing information for FVIII products will be updated as appropriate to add inhibitor development as a very common side effect in previously untreated patients and as uncommon in previously treated patients.
The warning on inhibitor development will be amended to state that low titers of inhibitors pose less risk of insufficient response than high titers.
1. Peyvandi F, Mannucci PM, Garagiola I et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med (2016), 374:2054-64.
2. Gouw SC et al. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood (2007), 109:4648-54.
3. Gouw SC et al. PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med (2013), 368:231-9.
4. Iorio A et al. Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series. Haemophilia (2017), 23:255-63.
5. Fischer K et al. Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project. Thromb Haemost (2015) 113:968-75.