Enhancing Clotting in Hemophilia: The Synergistic Effect of PF-06741086 and rFVIIa

Hemophilia, a genetic condition leading to excessive bleeding, is caused by a lack of either Factor VIII or IX in the blood's clotting process. A protein called tissue factor pathway inhibitor (TFPI) regulates blood clotting, and its overactivity can be problematic for hemophiliacs. PF-06741086 is a monoclonal antibody that targets TFPI to reduce its inhibitory effect, and it's being explored as a treatment for hemophilia types A and B, particularly for those with inhibitors.

In the study, the impact of PF-06741086 on the blood clotting process was examined alongside recombinant Factor VIIa (rFVIIa), which is commonly used to bypass clotting factor deficiencies. Experiments were conducted using plasma from severe hemophilia A patients, and the results showed that combining PF-06741086 with rFVIIa led to a significant increase in the production of thrombin, a key enzyme in clotting. This combination was found to be more effective than rFVIIa alone, as it not only increased peak thrombin levels but also reduced the time taken for clotting to occur.

Further analysis was conducted on additional hemophilia A plasmas, including those with inhibitors, as well as hemophilia B plasmas. The study consistently demonstrated that the addition of PF-06741086, either alone or with rFVIIa, enhanced thrombin generation. Notably, in samples with inhibitors, PF-06741086 was able to restore normal clotting activity on its own.

The research also measured the effect of PF-06741086 in non-hemophilic plasma, confirming that the addition of the antibody did not lead to excessive clotting. The study concluded that the combination of rFVIIa and PF-06741086 could be a promising therapeutic approach for hemophiliacs, as it effectively boosts thrombin generation without causing over-clotting.

The disclosures section indicates that several authors, including Rakhe, Hett, Murphy, and Pittman, are employed by Pfizer, the company developing PF-06741086.