A phase 1b/2, three-month study of marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), was conducted in participants with haemophilia A or B, with or without inhibitors. Participants assigned to four cohorts received escalating weekly doses based on inhibitor status (without inhibitors: 300 mg, a single 300-mg loading dose with subsequent 150-mg doses, or 450 mg; with inhibitors: 300 mg). Safety outcomes were treatment-emergent adverse events (TEAEs), injection site reactions, clinical and laboratory parameter changes. Efficacy was assessed by annualised bleeding rates (ABRs). Pharmacokinetics and pharmacodynamics (PD) were also evaluated. Among 26 treated participants [haemophilia A without inhibitor, n = 16 (61.5%); haemophilia A with inhibitor, n = 7 (26.9%); haemophilia B, n = 3 (11.5%)], 24 completed the study. Overall, 80.8% experienced TEAEs. ABR during treatment was significantly reduced versus an external on-demand control group (p < 0.0001) and versus pretreatment ABR (p < 0.0001), with significant reductions observed across all dose cohorts. Marstacimab exposure generally increased in a dose-related manner, with steady-state concentration reached by day 57. Changes in pharmacodynamic biomarkers occurred across all dose cohorts. Marstacimab was safe and well tolerated. Clinically meaningful reductions in ABR and treatment-related changes for all PD biomarkers indicated effective targeting of TFPI. (Clinicaltrials.gov identifier, NCT02974855).

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI -13·8 to -3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0·05 U/ml; 95% CI -0·07 to -0·02 and -4·77%; 95% CI -6·81 to -2·73, respectively). PAI-1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04-0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.