Third publication suggests recombinant FVIII product associated with higher risk of inhibitor development in newly diagnosed, previously untreated patients with severe hemophilia A 

On October 3, 2014, the World Federation of Hemophilia (WFH) issued a communique regarding a study published by a group in France that demonstrated a higher than expected incidence of  inhibitor development in previously untreated patients (PUPs) with severe hemophilia A treated with Kogenate FS/Bayer/Helixate NexGen compared to other recombinant factor VIII (rFVIII) products. Since then, a study published by a group from the UK has reported similar findings.

These results follow on from the unexpected results in the RODIN study, published in January 2013. That study was reviewed by regulators and in December 2013 the European Medicines Agency’s (EMA) Committee on Human Medicinal Products (CHMP) endorsed recommendations which concluded that the benefits of Kogenate FS/Bayer/Helixate NexGen continue to outweigh their risks in PUPs with hemophilia A. The EMA stated that the product information for this product should be amended to reflect the results of the RODIN study and clarify that there is no different risk between products.

Inhibitor development is caused by many risk factors, which makes it difficult to draw conclusions in a small patient population. At the moment, no firm conclusion can be made.

The WFH has requested that the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) examine all the relevant data and come to a conclusion as soon as possible. Both the FDA and the EMA have confirmed that they will be reexamining the data. In January 2015 the EMA confirmed it will work with the investigators of all of the relevant studies regarding Kogenate FS/Bayer/Helixate NexGen and inhibitors development in PUPs to make a recommendation for safe and effective use. This review is expected to take several months. It is the view of the WFH that all of the available data should be pooled in order to give a clearer answer about the relative risk for individual products.

Based on the currently available published data, it remains the position of the WFH that it may be prudent to consider not using Kogenate FS/Bayer/Helixate NexGen for newly diagnosed PUPs with severe hemophilia A where other safe clotting factor concentrates are available. There is no known increased risk for any other patients using these products.

The WFH will closely monitor this situation and will communicate again when further relevant information is available.

National Hemophilia Foundation Medical Advisory #417: MASAC Assessment on Inhibitor Studies

Updated March 2015