marstacimab for treating severe haemophilia B

NICE have stated that:

• marstacimab is recommended, within its marketing authorisation, as an option for preventing bleeding episodes caused by severe (factor IX [9] activity less than 1%) haemophilia B (congenital factor 9 deficiency) in people 12 years and over who:
  • weigh at least 35 kg and
  • do not have factor 9 inhibitors (anti-factor antibodies)

Marstacimab

Tissue factor pathway inhibitor (TFPI) antagonises early coagulation stages by inhibiting tissue factor‐activated FVII (FVIIa) and activated FX (FXa)

• TFPI is expressed in three isoforms, all sharing the Kunitz‐type inhibitor domain K2, which binds and inhibits activated FXa
• marstacimab is a human immunoglobulin G1 monoclonal antibody that targets the K2 domain of TFPI
  • intended to reduce the inhibition of FXa by TFPI, thereby augmenting haemostasis through the extrinsic pathway (2)
  • evidence showed that once‐weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long‐term efficacy up to 365 days (2)

The NICE committee noted:

• treatment for preventing bleeding episodes (prophylaxis) is usually factor 8 replacement therapy or emicizumab in severe haemophilia A, and factor 9 replacement therapy in severe haemophilia B
• in severe haemophilia A and B, evidence from a clinical trial shows marstacimab reduces the number of bleeding episodes a person has compared with factor 8 or 9 prophylaxis
• in severe haemophilia A, there is no trial directly comparing marstacimab with emicizumab
  • an indirect comparison suggests marstacimab reduces bleeding episodes by a similar number as emicizumab - but the evidence for this is uncertain
• in severe haemophilia B, the cost-effectiveness evidence for marstacimab showed it is a cost-effective option compared with factor 9

Reference:

1. NICE (June 2025). Marstacimab for treating severe haemophilia A or B in people 12 years and over without anti-factor antibodies
2. Mahlangu J et al. Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results. Br J Haematol. 2023 Jan;200(2):240-248.