Antibody Targeting Tissue Factor Pathway Inhibitor (TFPI) Sharply Reduces Bleeding Rate in Hemophilia A and B Patients

Subcutaneous administration of marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), resulted in a roughly 10-fold lower annualized bleeding rate (ABR) in 26 hemophilia patients than comparable control individuals in previous clinical trials who were treated on-demand with recombinant factor replacement therapy. This Phase Ib/II clinical study was sponsored by Pfizer, which is developing marstacimab for treatment of hemophilia A and B with and without inhibitors.

Sixteen (61.5 percent) and seven (26.9 percent) of treated study subjects had hemophilia A without and with inhibitors, respectively, and three (11.5 percent) had hemophilia B. Twenty-four of the 26 subjects had joints with a history of multiple bleeds (target joints). Once-weekly dosages ranged from 150 mg to 450 mg.

The mean ABR was 2.67 across all marstacimab-treated subjects, compared to an ABR of 27.62 in historical control subjects who received on-demand ReFacto (moroctocog alfa) or BeneFIX (nonacog alfa). Both TFPI and peak thrombin levels increased with marstacimab treatment, indicative of effective targeting of TFPI. Marstacimab was “generally safe and well-tolerated at all dose levels,” according to the investigators, with no thrombotic events or serious treatment-related adverse events. Decreases in circulating fibrinogen relative to baseline were observed at all dosage levels, but were not below the lower limit of the normal range and were reversible with treatment discontinuation.

An ongoing Phase III study (NCT03938792) evaluating marstacimab is enrolling a planned 145 adult and adolescent subjects with severe hemophilia A or moderately severe to severe hemophilia B. All participants are initially receiving a 300 mg loading dose followed by 150 mg weekly; a 300 mg weekly dosage is prescribed for those who meet dose escalation criteria.