PB0518 - Coagulation biomarker levels in subjects with severe hemophilia receiving acute treatment for bleeding episodes experienced during prophylactic marstacimab treatment

Background: Marstacimab is a human anti-TFPI monoclonal antibody currently in phase 3 development, intended for routine prophylaxis treatment to prevent or reduce the frequency of bleeding episodes in Hemophilia A or B patients (with or without inhibitors). Factor or bypass treatment for bleed events could lead to increased levels of downstream pharmacodynamic biomarkers associated with an increased risk of thrombosis.

Aims: Analysis of biomarker data in hemophilia patients with and without treated bleeding episodes receiving prophylactic marstacimab treatment was conducted to assess the changes in these biomarker levels post bleeding episodes.

Methods: Individual time profiles of peak thrombin, D-dimer and prothrombin fragments 1+2 (PF 1+2) levels in hemophilia patients receiving SC marstacimab (150 mg once weekly with a loading dose of 300 mg or 300 mg once weekly) from phase 2 and 3 studies were analyzed to assess the effect of bleed treatment. There were no thromboembolic events. All subjects with bleeding episodes were identified, along with the on-demand bleed treatment administered. Biomarker profiles were compared between subjects with and without bleed episodes, as well as with data from healthy volunteers, as these subjects represent an intact and uncompromised coagulation system.

Results: In general, elevated levels of peak thrombin, D-dimer and PF 1+2 were not seen following bleed treatment per protocol specified recommended guidelines (sample collection within and outside 4-day window). Biomarkers levels in patients were generally lower than or similar to those seen in healthy volunteers. Except for transient increases, biomarker levels were generally below 120 nM for peak thrombin, below 1 µg/mL for D-dimer and below 1200 pmol/L for PF 1+2.

Conclusion(s): The observed lack of excessive pharmacology following bleed treatment provides evidence against an increased risk of thrombosis post acute bleed treatment while on prophylactic marstacimab therapy and supports the clinical observations to date (absence of thromboembolic events).