A new study has found that recombinant factor IX-FIAV (FIX-FIAV) is effective in increasing thrombin formation and clotting activity in patients with hemophilia A, regardless of inhibitor status.
The study, published in the Journal of Thrombosis and Haemostasis, confirms previous studies that showed FIX-FIAV improved the hemophilia A phenotype in vitro and in vivo.
“Here we have assessed the prohemostatic effect of FIX-FIAV in a preclinical setting in plasma of patients with severe, moderate, or mild HA with and without FVIII inhibitor,” the authors explained. “This allowed us to not only evaluate the FIX-FIAV response regardless of residual and baseline FVIII levels, but to also study potential enhanced effects of FIX-FIAV in combination with [current hemophilia A therapies].”
The research team validated a novel factor IX variant, FIX-FIAV, in 21 adult patients with severe, moderate, or mild hemophilia A with or without inhibitors.
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All patients received their last does of FVIII concentrate at least 3 days before starting the study, and plasma was collected for analyses employing a modified FXIa-triggered thrombography assay to assess the prohemostatic effect of FIX-FIAV alone and together with current therapies.
The beneficial, FVIII-independent effect of FIX-FIAV was confirmed by administering a FVIII-inhibitory antibody to the plasma samples. The results showed that 100% FIX-FIAV improved the median FVIII-equivalent activity to various degrees in the plasma of patients with severe, moderate, and mild hemophilia A.
The results also demonstrated that the combination of FIX-FIAV with current therapies had a modest effect on thrombin generation lag time, meaning FIX-FIAV could represent a new treatment for patients with hemophilia A with inhibitors, regardless of their current therapy.
The authors caution that the small sample size represents a limitation, and they recommend further clinical studies in patients with hemophilia A with and without FVIII inhibitors to assess the hemostatic effects of FIX-FIAV.
Strijbis V, Romano LGR, Cheung KL, et al. A factor IX variant that functions independently of factor VIII mitigates the hemophilia A phenotype in patient plasma. J Thromb Haemost. Published online February 22, 2023. doi:10.1016/j.jtha.2023.02.019