CT-001, a novel next generation factor viia, demonstrates enhanced procoagulant activity in peripartum patient samples

Severe postpartum hemorrhage (PPH) unresponsive to first- and second-line therapies is treated with massive transfusion and aggressive procedures to compensate for and control blood loss. Recombinant factor VIIa (rFVIIa) has demonstrated some efficacy in this scenario, but has limited use due to thromboembolic risks. To address this liability, CT-001, a novel next generation rFVIIa, was developed to increase safety and improve activity. CT-001 has 4 N-glycans with terminal sialic acid residues removed to promote active clearance via the asialoglycoprotein receptor for lower thrombogenicity risk, and P10Q/K32E substitutions introduced to its gamma-carboxyglutamic (Gla)-domain for enhanced activity (Fig 1). While previous in vitro and in vivo studies support the success of these efforts (Sim DS et al, Thromb Res 2022 215:58), we sought to assess the ex-vivo hemostatic activity of CT-001 in peripartum blood samples.