Use of the human monoclonal antibody marstacimab is safe and effective for the treatment of patients with hemophilia A and hemophilia B, according to study results recently published in the British Journal of Haematology.

A phase 1/2, open-label, multicenter study (NCT02974855) of marstacimab was conducted over 3 months. The researchers sought to assess the short-term safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of weekly subcutaneous injections of marstacimab. The agent was administered for up to 3 months in participants with severe hemophilia A or hemophilia B, with or without inhibitors, after which time the patients were eligible to enroll in a phase 2, long-term treatment study.

Marstacimab is known to target the tissue factor pathway inhibitor (TFPI), which antagonizes early coagulation states by inhibiting tissue factor–activated coagulation factor VII and activated factor X.

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The study was carried out at 8 centers in North America, South America, Europe, and Asia. Eligible participants were males aged 18 to 65 years with hemophilia A or hemophilia B, with or without inhibitors, who had previously been treated on demand and had 6 or more acute, nonsurgical, treated bleeding episodes in the 6 months prior to screening.

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All participants were assigned to 1 of 4 cohorts. Those individuals without inhibitors were assigned, through an interactive technology system, to subcutaneous marstacimab at dose levels of 300 mg once weekly (the 300-mg cohort); a single 300-mg loading dose, followed by 150 mg once weekly (the 300-mg/150-mg cohort); or 450 mg once weekly (the 450-mg cohort). For those with inhibitors, 300 mg once weekly was used (the 300-mg with inhibitors cohort).

Safety outcomes included treatment-emergent adverse events (TEAEs), injection-site reactions, and changes in clinical and laboratory parameters. Efficacy was evaluated with the use of annualized bleeding rates (ABRs). Among 26 treated participants—16 of whom had hemophilia A without inhibitors, 7 of whom had hemophilia A with inhibitors, and 3 of whom had hemophilia B—24 individuals completed the study.

Overall, 80.8% of the participants experienced TEAEs, with the events classified as “serious” in 15.4% of participants. The most common were injection site pain and swelling and hypertension.

ABRs during marstacimab therapy were statistically significantly reduced compared with an external on-demand control group (P <.0001), as well as with pretreatment ABRs (P <.0001). In fact, significant reductions were observed across all of the dose cohorts.

Marstacimab exposure generally increased in a dose-related fashion over the 300-mg to 450-mg dose range after both single-dose and multiple-dose administration. Steady-state concentration was achieved by day 57. Changes in PD biomarkers were reported across all dose cohorts.

“Clinically meaningful reductions in ABR and treatment-related changes for all PD biomarkers indicated effective targeting of TFPI,” investigators wrote.


Mahlangu JN, Lamas JL, Morales JC, et al. A phase 1/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia. Br J Haemotol. Published online August 23, 2022. doi:10.1111/bjh.18420

PF-06741086 multiple dose study in severe hemophilia. November 29, 2016. Updated December 4, 2019. Accessed August 29, 2022.