PF-05230907 (FXaI16L) is a zymogen-like variant of recombinant activated coagulation factor X (FXa), which is more resistant to inactivation by plasma protease inhibitors (compared to endogenous FXa). Previous studies showed that its cofactor, Factor Va (FVa), facilitates its transition to an active conformation, promoting hemostatic activity. The properties of PF-05230907 are consistent with its use as a short acting hemostatic agent to control bleeding and it currently is in clinical development for treatment of individuals with intracerebral hemorrhage (ICH).

We conducted a Phase 1 First-in-Human study to determine if single escalating doses of PF-05230907 were safe and tolerable and to characterize pharmacokinetics (PK) and pharmacodynamics (PD). The study was conducted in healthy adult volunteers aged 18-35 years with no risk factors for thrombosis and was approved by the local ethics committee. Subjects were assigned to one of six ascending single dose cohorts, each with 2 placebo treated subjects and 6 subjects treated with PF-05230907 (0.1, 0.3, 1, 2, 3, or 5 µg/kg). Assessments included safety monitoring, PD, PK, and immunogenicity testing. All placebo treated subjects were to be included in the safety and PD analyses. All PF-05230907 treated subjects were to be included in the safety, PK and PD analyses.

Forty-nine male subjects were enrolled after informed consent. One subject from the 2 µg/kg cohort received less than 80% of the planned PF-05230907 dose and was replaced. This subject was included in the safety analysis, but excluded in PK and PD analysis. PF-05230907 exhibited a fast clearance rate with a terminalhalf-life of approximately 4 minutes. Exposure of PF-05230907 appeared to increase proportionally with dose. Treatment-related PD changes were observed for activated partial thromboplastin time (aPTT), thrombin-anti-thrombin III complexes, prothrombin fragment 1+2, D-dimer and thrombin generation assay (lag time and peak thrombin). PF-05230907 was safe and well tolerated at all dose levels tested with no dose limiting toxicity. There were no serious adverse events. One subject treated with PF-05230907 had a weak and transient non-neutralizing anti-drug antibody response, which did not cross react with native FX or native FXa.

PF-05230907 was safe and tolerated and exhibited pharmacologic effect in healthy adults when administered at doses up to 5 µg/kg. The safety profile, PK, and PD observed in this study support further development of PF-05230907 for hemostatic treatment in individuals with acute hemorrhagic conditions.


Arkin:Pfizer Inc: Employment. Hua:Pfizer Inc: Employment. Kantaridis:Pfizer Inc: Employment. Li:Pfizer Inc: Employment. Parsons-Rich:Pfizer Inc: Employment. Pittman:Pfizer: Employment.

Author notes


Asterisk with author names denotes non-ASH members.

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