Marstacimab Shows Promising Efficacy in Hemophilia Management: Study
Canada: The phase 3 BASIS trial demonstrated that marstacimab, a TFPI-targeting therapy enhancing thrombin generation independently of FVIII and FIX, significantly reduced annualized bleeding rates (ABR) in patients with hemophilia A or B after 12 months of once-weekly treatment. The findings highlight its superiority over prior on-demand and routine prophylaxis therapies.
The study, published in the Blood journal by Davide Matino and colleagues from the Thrombosis and Atherosclerosis Research Institute, McMaster University, Canada, evaluated the efficacy and safety of marstacimab, a monoclonal antibody designed to inhibit the tissue factor pathway inhibitor (TFPI) and restore hemostatic balance. Marstacimab has previously shown promise in phase 1 and 2 trials, demonstrating safety and effectiveness in adults with severe hemophilia A (HA) or B (HB).
BASIS was an open-label, phase 3 trial including males aged 12 to 74 years with severe HA (factor VIII <1%) or moderately severe to severe HB (factor IX ≤2%) who did not have inhibitors. Participants first underwent a 6-month observational phase (OP) while receiving either on-demand (OD) or routine prophylaxis (RP) therapy. This was followed by a 12-month active treatment phase (ATP) during which participants received once-weekly subcutaneous 150 mg marstacimab. The primary endpoints were ABR for treated bleeds compared with the observational phase and safety.
The findings from the trial were as follows:
- Of the 128 participants enrolled, 116 received marstacimab.
- In the on-demand (OD) group (n = 33), mean annualized bleeding rate (ABR) decreased from 39.86 to 3.20.
- The ABR reduction in the OD group demonstrated the therapy’s superiority (estimated ABR ratio 0.080).
- In the routine prophylaxis (RP) group (n = 83), mean ABR decreased from 7.90 to 5.09.
- The ABR reduction in the RP group confirmed both noninferiority and superiority (estimated ABR difference –2.81).
- No deaths occurred during the trial.
- No thromboembolic events were reported.
- Marstacimab was generally well-tolerated with no unexpected side effects.
The results highlight marstacimab’s potential to transform hemophilia management by offering a once-weekly subcutaneous alternative to conventional factor replacement therapies. Unlike factor-based treatments, marstacimab works independently of FVIII or FIX levels, making it effective for both hemophilia A and B patients without inhibitors. The therapy’s consistent safety profile, with no thromboembolic events reported, also distinguishes it from other non-factor agents under development.
While the study’s sample size limits full characterization of rare thrombotic events, the trial provides robust evidence of marstacimab’s effectiveness and safety over 12 months. Despite challenges posed by the COVID-19 pandemic, including potential treatment interruptions, the trial’s conduct and data integrity were largely maintained.
The BASIS trial demonstrates that once-weekly subcutaneous marstacimab prophylaxis significantly lowers bleeding rates and is well tolerated in adolescents and adults with severe hemophilia A or moderately severe to severe hemophilia B without inhibitors.
"Its convenience, efficacy, and safety suggest that marstacimab could become a valuable addition to the hemophilia treatment landscape, expanding options for patients who currently rely on factor replacement or more frequent therapies," the authors concluded.
Reference:
Matino D, Palladino A, Taylor CT, Hwang E, Raje S, Nayak S, McDonald R, Acharya SS, Mahlangu J, Jiménez-Yuste V, Choraria N, Yang R, Li CK, Al-Khabori M, Wali Y, Morales Adrián J, Park YS, Zülfikar OB, Teeter J. Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial. Blood. 2025 Oct 2;146(14):1654-1663. doi: 10.1182/blood.2024027468. PMID: 40608864.
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