Efficacy and Safety of Marstacimab Prophylaxis in Hemophilia A/B With Inhibitors: Results from the Phase 3 BASIS Trial Open Access

• Marstacimab inhibits TFPI, enhancing factor Xa and thrombin generation to restore hemostasis in hemophilia A or B.

• In participants with inhibitors, weekly subcutaneous injections of marstacimab reduced bleeding rates with no unanticipated side effects.

Marstacimab is a monoclonal antibody that inhibits tissue factor pathway inhibitor and is approved for prophylactic use in individuals with hemophilia A or B without inhibitors. We present results on the efficacy and safety of marstacimab in individuals with inhibitors. BASIS (NCT03938792) was a phase 3, open-label, single-arm study to evaluate once-weekly subcutaneous flat-dose marstacimab in males aged 12 to <75 years with severe hemophilia A or moderately severe to severe hemophilia B. Participants with inhibitors received bypassing agents (on-demand or routine prophylaxis) during a 6-month observational phase (OP) before entering a 12-month active treatment phase (ATP) with marstacimab. Primary endpoints were annualized bleeding rate (ABR) of treated bleeds and safety. Of 60 participants with inhibitors in the OP, 51 entered the ATP and received marstacimab. In the on-demand group (n=48), mean (95% confidence interval [CI]) estimated ABR declined from 19.78 (16.12-24.27) in the OP to 1.39 (0.85-2.29) during the ATP (ABR ratio 0.07 [0.042-0.118]; 2-sided P<.0001). Results were consistent by hemophilia type (ABR ratio 0.05 [hemophilia A, n=40]; 0.13 [hemophilia B, n=8]). Participants reported significant improvements in health-related quality of life. Adverse events were common but mostly mild; 1 treatment-related grade 3 skin rash led to discontinuation. Antidrug antibodies were detected in 19.6% of participants, with no apparent effect on efficacy or safety. In participants with inhibitors, marstacimab was associated with reduced bleeding rates and an acceptable safety profile, with no thromboembolic events. Marstacimab may be a viable treatment option for people with hemophilia A or B with inhibitors. This trial is registered at www.clinicaltrials.gov as # NCT03938792.