If proven safe and effective in patients, the investigational therapy could provide an alternative preventive solution to standard replacement therapy.
The study, “Marstacimab, a tissue factor pathway inhibitor neutralizing antibody, improves coagulation parameters of ex vivo dosed haemophilic blood and plasmas,” was published in the journal Haemophilia.
Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein naturally produced in the body that inhibits an alternative process of blood coagulation in its early phases.
This has led researchers to consider the inhibition of TFPI as an alternative approach to factor replacement therapy for bypassing coagulation problems and preventing bleeding in hemophilia patients.
To look at the effectiveness of this strategy, researchers tested if a human antibody that blocks TFPI — marstacimab — was able to restore coagulation in hemophilic blood and plasma.
By blocking TFPI, marstacimab was expected to prevent its activity and allow blood clotting by the alternative process in patients with hemophilia.
They collected blood and plasma from 12 participants who had hemophilia A (factor VIII, or FVIII, deficiency) or hemophilia B (factor IX, or FIX, deficiency), regardless if they had inhibitory antibodies.
Samples were trialed in the laboratory (or ex vivo) where they were exposed to a placebo solution, marstacimab, or the missing recombinant factor (FVIII or FIX) to simulate replacement therapy.
Several coagulation assays were performed to determine how well and how quickly blood and plasma coagulated with each of these agents, and how they affected the production of thrombin, a factor essential for the formation of blood clots.
Data showed that the addition of marstacimab was able to induced pro‐coagulant responses in hemophilic blood, shortening the clotting time in all patient samples. Similarly, plasmas treated with marstacimab produced more thrombin and clotted more rapidly.
Marstacimab’s effects were comparable to those of recombinant FVIII or FIX and at similar concentrations. Researchers also confirmed that the effects of marstacimab were consistent and reproducible, by comparing experiments done with the agent on blood collected from the same study participants on different days.
“These studies show the ex vivo potency of marstacimab in restoring hemostasis [coagulation] in whole blood and plasmas from hemophilia participants and comparability to ex vivo reconstitution with recombination coagulation factors,” the researchers wrote.
Marstacimab (previously PF‐06741086) is being developed by Pfizer as a preventive coagulant therapy for hemophilia A and B patients with or without inhibitors. The experimental therapy was granted orphan drug designation by both the U.S. Food and Drug Administration and the European Medicines Agency.
A first‐in‐human Phase 1 clinical trial (NCT02531815) demonstrated the safety, tolerability, and favorable distribution in the body of the therapy in healthy volunteers.
A Phase 1/2 trial (NCT02974855), recently completed, evaluated the safety and efficacy of multiple subcutaneous (under the skin) and/or intravenous (into the vein) doses in adults with severe hemophilia.
Pfizer also has plans for a Phase 3 trial (NCT03938792) in the U.S. to test marstacimab in teenagers and adults from 12 to 74 years of age.
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