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.
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. ClinicalTrials.gov. November 29, 2016. Updated December 4, 2019. Accessed August 29, 2022.