Management of breakthrough bleeds and surgical procedures in participants with hemophilia A or B without inhibitors receiving marstacimab prophylaxis in the phase 3 BASIS study.

BACKGROUND: Marstacimab, a subcutaneous anti-tissue factor pathway inhibitor monoclonal antibody, has demonstrated efficacy in reducing treated bleeds in severe hemophilia A or moderately severe to severe hemophilia B without inhibitors in the phase 3 BASIS study. Evidence guiding management of breakthrough bleeds and perioperative hemostasis during marstacimab prophylaxis remains limited. OBJECTIVES: Describe the frequency, treatment, and outcomes of breakthrough bleeds and surgical/medical procedures in participants without inhibitors receiving marstacimab prophylaxis. METHODS: After the 6-month observation phase, participants received a 300-mg marstacimab loading dose followed by 150 mg once weekly in a 12-month active treatment phase (ATP). Bleed incidence, factor replacement therapy (FRT) use, and perioperative management were analyzed descriptively due to the small sample size and event distribution. RESULTS: Of 116 participants in the ATP, 75 (64.7%) experienced 453 acute breakthrough bleeds and were treated with FRT; 83% were controlled with a single infusion, most often standard half-life recombinant or plasma-derived factor VIII/IX. Thirteen participants underwent 15 procedures (8 dental, 7 other), with marstacimab continued in 86.7% and FRT used in 13/15 (86.7%). No thromboembolic events occurred during ATP. CONCLUSIONS: Breakthrough bleeds were generally controlled with standard FRT, with most requiring only one infusion. Perioperative management of minor procedures was feasible without interruption of marstacimab, with FRT use comparable to other non-factor prophylactic agents. Data on major surgery are lacking due to study exclusions, and conclusions should be restricted to minor and dental procedures. Further studies are needed to define perioperative protocols for higher-risk interventions. (ClinicalTrials.gov number, NCT03938792).