Abstract
We report results of the first real world study evaluating outcomes in people with severe and non-severe hemophilia (SH, NSH), including the first female patient on Marstacimab, a novel Anti TFPI antagonist. Over the past decade, the management of hemophilia has undergone radical transformation with the emergence of novel non-factor therapies, particularly subcutaneous agents that rebalance hemostasis. Traditionally, the cornerstone of care for people with hemophilia (pwh) has been the use of intravenous clotting factor concentrates (CFCs) and FVIII mimetics for hemophilia A, which, while effective, present challenges in terms of administration burden and variable bleed control, especially in subpopulations not captured in clinical trials (Srivastava et al., 2020). Recent approval of rebalancing agents—including Marstacimab, a tissue factor pathway inhibitor (TFPI) monoclonal antibody for people with hemophilia A and B without inhibitors, along with Fitusiran and Concizumab—herald a new era of expanded, and effective patient-friendly therapeutic options.
To date, regulatory approvals and pivotal trials have focused predominantly on severe hemophilia (factor VIII or IX activity <1%), often excluding non-severe (1–5% activity) and female pwh. However, mounting evidence has revealed that individuals outside the “severe” category—namely symptomatic females with hemophilia and NSH males—can experience considerable bleeding burden and hemophilic arthropathy. Herein, we present real-world data on the use of Marstacimab in symptomatic females and moderate males with hemophilia A or B.
Results: 7 participants on weekly injectable subcutaneous (SQ) Marstacimab at 150mg/dose as solo prophylaxis (6 males - 3 SH, 3NSH 1 NSH female. Ages 15-19 years) are reported here. 50% switched from a CFC based prophylaxis while the remaining switched to weekly SQ regimen from on demand therapy in the moderate cohort whereas 75% of severe Hemophilia A/B patients switched from CFC and remaining from previous Emicizumab prophylaxis. Experience of trauma related breakthrough bleed in the female patient while on Marstacimab, demonstrated excellent clinical hemostasis, despite a bone fracture, needing a single dose of CFC for peri surgical intervention while on Marstacimab weekly prophylaxis. All subjects demonstrated excellent bleed control with zero reported spontaneous breakthrough bleeds while on weekly SQ regimen. 100% report improved quality of life metrics, mobility scores and reported convenience of the SQ therapy reducing treatment burden and associated needle phobia. No unexpected adverse events or thromboembolism have been noted in these patients despite having higher baseline factor VIII/IX activity than participants during the preceding clinical trial reporting (factor activity <1%). Joint health (HJHS), chronic pain, anemia/iron status, menstrual bleeding (female) were additional metrics collected and are being monitored in these cohorts longitudinally.
Conclusion: Our findings underscore the critical need to consider bleeding phenotype—not merely factor levels—when selecting candidates for rebalancing therapies. Women with hemophilia endure recurrent, debilitating bleeds related to menorrhagia or obstetric complications, resulting in chronic anemia and impaired quality of life. By broadening the focus beyond severe hemophilia, we advocate for an evolution in treatment paradigms that prioritizes individual bleeding risk, closing the persistent care gap for males and females with non-severe hemophilia, especially since labeling of anti-TFPI agents such as Marstacimab is not limited by factor level or gender. Furthermore, we strongly advocate for inclusion of women with hemophilia in clinical trials using novel agents based on their bleeding phenotype and regardless of their factor levels.
