WFH NETWORK

Recombinant FVIII product associated with higher risk of inhibitor development in newly diagnosed, previously untreated patients with severe hemophilia A 

A study published in the journal Blood on September 24, 2014 suggests that inhibitor incidence is elevated in previously untreated patients (PUPs) with severe hemophilia A treated with Kogenate FS/Bayer/Helixate Nexgen compared to other recombinant factor VIII (rFVIII) products. It should be noted that Kogenate FS/Bayer/Helixate Nexgen have been marketed for over a decade and have a good safety record. No increased inhibitor risk has been found for previously treated patients (PTPs). The development of inhibitors is a known risk for all factor VIII products; however, this is the second study suggesting an increased risk with this specific product.

In January 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpected higher risk of inhibitor development in PUPs treated with this second-generation full-length rFVIII, Kogenate FS/Bayer/Helixate Nexgen. 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 CHMP also stated that the product information for these medicines should be amended to reflect the results of the RODIN study. The manufacturer initiated an update to their product label. 

The newly published study focused on 303 boys with severe hemophilia A first treated with a rFVIII product. The inhibitor incidence was higher with Kogenate FS/Bayer/Helixate NexGen versus the most widely used rFVIII product. Similar results were found for high-titer inhibitors and in sensitivity analyses. The researchers believe these results suggest the higher immunogenicity of Kogenate FS/Helixate NexGen compared to other rFVIII products in newly diagnosed PUPs with severe hemophilia A.

The WFH has requested that the US Food and Drug Administration (FDA) and EMA examine all the relevant data in an expedited manner. Based on the available published data, it may be prudent, where other safe clotting factor concentrates are available, to consider not using Kogenate FS/Bayer/Helixate NexGen for newly diagnosed PUPs with severe hemophilia A. There is no evidence of a higher risk of inhibitors with this product in PTPs.

Data related to the immunogenicity of treatment products is constantly evolving; WFH supports the detailed and rapid publication of all relevant clinical and trial data to allow for a full and independent evaluation of the benefits and potential harms of treatment. The WFH will closely monitor this situation and will communicate again no later than November 17.

Bayer Global Position Statement


Updated October 2014