Marstacimab, a tissue factor pathway inhibitor neutralizing antibody, improves coagulation parameters of ex vivo dosed haemophilic blood and plasmas

• DOI: 10.1111/hae.13820
• Publication Date: 2019-07-23T22:34:41Z
• Authors: Sunita Patel‐Hett; Erika J. Martin; Bassem M. Mohammed; Swapnil Rakhe; Pengling Sun; John C. Barrett; Melinda E. Nolte; Janice Kuhn; Debra D. Pittman; John E. Murphy; Donald F. Brophy
• Keywords: Ex vivo; Thromboelastometry; Clotting time; Factor IX

Tissue factor pathway inhibitor (TFPI) is an endogenous of the extrinsic that negatively regulates thrombin production during coagulation. Under haemophilic conditions, where intrinsic coagulation impaired, inhibition TFPI may improve clotting.We investigated ex vivo effects a human neutralizing antibody, marstacimab (previously PF-06741086), in assays including rotational thromboelastometry (ROTEM), generation assay (TGA) and dilute prothrombin time (dPT) assay, performed whole blood plasmas. We compared to recombinant factors reproducibility restoring haemostasis by comparing its effect collected from same study participants on differing days.Citrated plasmas obtained haemophilia were supplemented with vehicle, marstacimab, FVIII (rFVIII) or IX (rFIX) analysed ROTEM, TGA dPT using low tissue concentrations trigger coagulation.Marstacimab induced pro-coagulant responses ROTEM parameters reduction clotting times increases angle. Similarly, participant exhibited improvements parameters, reduced lag times, increased peak reductions time. Concentrations tested showed activity comparable addition rFVIII rFIX reproducible.These studies show potency comparability reconstitution recombination factors.