May, 2016 – The results of the SIPPET (Survey of Inhibitors in Plasma-Products Exposed Toddlers) study were published today in the New England Journal of Medicine. The paper suggests that, in previously untreated patients (PUPs), the risk of developing an inhibitor when using recombinant factor VIII products is higher than when using plasma-derived factor VIII concentrates. This is a significant study and the results may prove to be important. There is no evidence of a higher risk of inhibitors with recombinant FVIII in previously treated patients (PTPs).
Between 2010 and 2014, PUPs with severe hemophilia A were treated at 42 participating sites in 14 countries from Africa, Asia, the Americas, and Europe. In the study, 251 PUPs were randomized so that 125 patients received plasma-derived FVIII (which contained von Willebrand factor) and 126 received recombinant FVIII. The study used a variety of plasma-derived and recombinant FVIII clotting factor concentrates. The study compared two classes of FVIII concentrates – plasma-derived and recombinant – so no conclusions can be made about the risk associated with specific products. It should also be noted that some newer recombinant FVIII products were not included in the SIPPET study.
Inhibitors are a known risk with any clotting factor concentrate and the SIPPET study shows that inhibitors occur often in PUPs treated with either class of product. It is also widely known that inhibitor development is caused by many risk factors not related to product type. However, the possibility that in PUPs the risk may be elevated with recombinant products, means it may be prudent, where there is a choice, to consider not using recombinant FVIII to treat newly diagnosed patients with severe hemophilia A.
The WFH awaits comment from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). We will continue to monitor this situation and provide updates when available.
The paper can be viewed here: http://www.nejm.org/doi/full/10.1056/NEJMoa1516437?query=featured_home
The EMA’s review procedure can be viewed here:http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Factor_VIII/human_referral_prac_000060.jsp&mid=WC0b01ac05805c516f