EMA concludes review of human factor VIII medicines authorized in EU

The European Medicines Agency has concluded that there is no clear and consistent evidence of a difference in the incidence of inhibitor development between the two classes of factor VIII medicines: those derived from plasma and those made by recombinant DNA technology.

The EMA’s review was started following publication of the SIPPET study, which concluded that recombinant factor VIII medicines had a higher incidence of inhibitor development than plasma-derived medicines. The review also covered other relevant interventional clinical trials and observational studies. When all these data were examined, they did not provide clear evidence of a difference in risk of inhibitor development between the two classes of medicines.

Factor VIII is needed for blood to clot normally and is lacking in patients with hemophilia A. Factor VIII medicines replace the missing factor VIII and help control and prevent bleeding. However the body may develop inhibitors as a reaction to these medicines, particularly when patients first start treatment. The inhibitors reduce the medicines’ effect, so bleeding is no longer controlled.

Due to the different characteristics of individual products within the two classes, the EMA concluded that the risk of inhibitor development should be evaluated individually for each medicine, regardless of class. The risk for each product will continue to be assessed as more evidence becomes available.

To reflect current knowledge, the prescribing information of factor VIII medicines will be updated to include, as appropriate, inhibitor development as a very common side effect in previously untreated patients, and as an uncommon side effect in previously treated patients. The warning on inhibitor development will be amended to state that low levels of inhibitors pose less risk of severe bleeding than high levels.