Long‐term safety and efficacy of the anti‐tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results

Summary Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in patients with haemophilia. This multicentre, open‐label study investigated safety, tolerability, and efficacy of long‐term weekly prophylactic marstacimab treatment in participants with severe haemophilia A and B, with or without inhibitors. Adult participants were enrolled from a previous phase Ib/II study or de novo and assigned to one of two subcutaneous (SC) marstacimab doses: once‐weekly 300 mg or a 300‐mg loading dose followed by once‐weekly 150‐mg doses, for up to 365 days. Study end‐points included safety assessments and annualised bleeding rates (ABRs). Of 20 enrolled participants, 18 completed the study. Overall, 70% of participants had treatment‐emergent adverse events, including injection site reactions, injection site haematoma, and haemarthrosis. No treatment‐related serious adverse events or thrombotic events occurred. Across all dose cohorts, mean and median on‐study ABRs ranged from 0 to 3.6 and 0 to 2.5 bleeding episodes/participant/year respectively, demonstrating comparable efficacy to that observed in the short‐term parent study. No treatment‐induced anti‐drug antibodies were detected. Once‐weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long‐term efficacy up to 365 days. ( Clinicaltrials.gov identifier, NCT03363321).