Abstract Number: PB0699
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Rare Bleeding Disorders
Background: Marzeptacog Alfa (Activated) (MarzAA), a novel high potency rFVIIa, is being developed for subcutaneous (SQ) treatment of bleeding in Factor VII deficiency (FVIID) and other rare bleeding disorders. Patients with a severe phenotype can have life threatening bleeding and reduced quality of life.
Aims: To investigate the effect of SQ MarzAA on bleeding after tail vein transection (TVT) in a rat model of FVIID.
Methods: Sprague Dawley rats were treated with intravenous (IV) vehicle or warfarin 0.3 mg/kg to induce FVIID. Blood samples were obtained 1 to 4 hours after dosing to assess prothrombin time (PT) and activated partial thromboplastin time (aPTT) and 3 hours after dosing was chosen to investigate SQ MarzAA treatment (Table 1). Rats were placed under isoflurane anesthesia for the TVT procedure. Rats were treated with increasing doses of SQ MarzAA at either two hours before or one minute after TVT. The tail was briefly immersed in saline and then a lateral vein transected at 5 mm in diameter. Subsequent bleeding was monitored for 60 minutes and total blood loss quantified by measurement of hemoglobin in the saline.
Results: Dosing with warfarin induced a window when the PT was significantly prolonged while the aPTT was minimally affected (Table 1); this period represents a functional FVIID without overtly inducing concurrent defects of other factors traditionally affected by warfarin, including prothrombin, Factors IX and X.
SQ MarzAA administered prior to TVT reduced blood loss in a dose dependent manner (Figure 1) and was completely normalized at the highest dose. Notably, SQ MarzAA also decreased blood loss when used on-demand 1 minute after injury.
Conclusions: SQ MarzAA successfully treated induced bleeding in FVIID rats. These results provide robust nonclinical evidence that SQ MarzAA has the potential for prophylaxis or on-demand treatment of bleeding in patients with FVIID.
To cite this abstract in AMA style:
Knudsen T, B Johansen P, Neuman L, Levy H, Reckless J, E Blouse G. Subcutaneous Marzeptacog Alfa (Activated) is Effective Treatment of Bleeding in FVII Deficient Rats [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/subcutaneous-marzeptacog-alfa-activated-is-effective-treatment-of-bleeding-in-fvii-deficient-rats/. Accessed March 21, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/subcutaneous-marzeptacog-alfa-activated-is-effective-treatment-of-bleeding-in-fvii-deficient-rats/