An Ex Vivo Pharmacodynamic Study of KN057, a Tissue Factor Pathway Inhibitor Neutralizing Antibody, in Plasma Samples From Patients With Haemophilia or VWD3.

INTRODUCTION

Tissue factor pathway inhibitor (TFPI), a key regulator of tissue factor-initiated coagulation through FXa-dependent inhibition of the tissue factor-FVIIa complex, has emerged as a promising target for restoring thrombin generation.

AIM: This ex vivo pharmacodynamic study aimed to evaluate the KN057, a novel humanized TFPI-neutralizing antibody, in plasma samples from participants with haemophilia or type 3 von Willebrand disease (VWD3).

METHODS

In this ex vivo spiking study, plasmas obtained from haemophilia or VWD3 participants were supplemented with KN057 at the concentration of 0-140.00 nM. The thrombin generation assay (TGA) and the dilute prothrombin time (dPT) assay were performed to assess coagulation responses.

RESULTS

Between 26, May 2021, and 3, September 2021, a total of 29 participants were enrolled in this study, including 10 haemophilia A (HA) without inhibitors, 6 haemophilia B (HB) without inhibitors, 6 HA with inhibitors, 3 HB with inhibitors, and 4 VWD3. In participant plasmas supplemented with KN057, peak thrombin and endogenous thrombin potential (ETP) increased notably between 1.12-5.60 nM, and reached a maximal level at 28.00 nM. A dose-dependent decrease in dPT was observed in all participants with haemophilia or VWD3.

CONCLUSIONS

KN057 exhibited a consistent ex vivo pharmacodynamic profile, including both the response trend and effective concentration range, across plasma samples from patients with HA or HB, irrespective of inhibitor status. Furthermore, its pharmacodynamic activity in plasma from patients with VWD3 was comparable to that observed in haemophilia plasma.