Hemophilia A: EMA Starts Third Review of Factor VIII-Containing Products

The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has initiated a review of factor VIII-containing medicines, to evaluate the risk of inhibitor protein development in patients starting treatment for hemophilia A, according to a press release.

This review, which will cover all medicines containing factor VIII authorized in the European Union, follows a recent study that suggested such inhibitors are developed more frequently in patients receiving the medicines engineered by recombinant DNA technology in animal cell lines, than in patients treated with early replacement therapy with human plasma-derived factor VIII.

The study was published in the New England Journal of Medicine (NEJM).

Factor VIII is a clotting protein that helps prevent and control bleeding in patients with hemophilia A. Medicines containing the protein can be extracted from blood plasma and are called human blood-derived factor VIII medicines; or they can be produced by biotechnology methods which are called recombinant factor VIII products.

The development of inhibitors, neutralizing antifactor VIII alloantibodies, is a challenge in treatment with both types of medicines. It is especially prone to occur in patients using the treatment for the first time – and can lead to the loss of bleeding control.

EMA previously conducted two reviews addressing risk for inhibitor development with recombinant factor VIII products. First, in 2013 after a study indicated that almost a third of untreated children with hemophilia A developed antibodies against two recombinant factor VIII products, Kogenate Bayer and Helixate NexGen. The second time happened in 2014 with the same products. Both times, PRAC concluded that the evidence did not prove an increased risk of inhibitor development compared to other products.

EMA will review the results of the NEJM study and other relevant data on blood-derived and recombinant factor VIII medicines. The review, initiated after a request by the Paul-Ehrlich-Institut, aims to assess the implications of the data on previously untreated patients and to determine if there is need to change marketing authorizations. The Co-ordination Group for Mutual Recognition and Decentralised Procedures–Human will then assess the PRAC recommendations and adopt a position.