Factor VIII medicines: no clear and consistent evidence of difference in risk of inhibitor development between classes
Press release
Human
EMA concludes review of human factor VIII medicines authorised in EU
The European Medicines Agency (EMA) 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.
EMA's review was started following publication of the SIPPET study (1), 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 haemophilia 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, 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.
Information for patients
Information for healthcare professionals
References
The review looked at data from studies including:
Information on previous EMA reviews of factor VIII medicines can be found here:
More about the medicine
The review covers all medicines containing human factor VIII authorised in the European Union. Factor VIII is a clotting protein and these medicines are used to temporarily increase levels of this protein in patients with haemophilia A, helping to prevent and control bleeding.
Human plasma-derived factor VIII medicines are extracted from blood plasma. Recombinant factor VIII products, on the other hand, are produced by a method known as 'recombinant DNA technology': they are made by cells into which a gene (DNA) has been introduced to enable the cells to produce factor VIII.
Human factor VIII medicines include nationally authorised and centrally authorised products containing the active substances human coagulation factor VIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa and turoctocog alfa.
More about the procedure
The review of factor VIII medicines was initiated on 7 July 2016 at the request of the German medicines authority Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.
The review was first carried out by EMA's Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations.
Following a request from a company concerned, the PRAC re-examined its initial recommendations. The PRAC's final recommendations were sent to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which has adopted the Agency's opinion.
The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States in due course. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.