Characterizing the Effects of NN1731 and rFVIIa In Severe Hemophilia Patients with a Poor Laboratory Response to In Vivo Dosing of rFVIIa 90 μ g/Kg

Abstract Abstract 4414 Introduction: A rFVIIa analogue (NN1731) with increased prothrombinase activity on the activated platelet surface relative to rFVIIa has been shown to result in a more rapid and less variable response in spiking experiments with hemophilia whole blood samples. In a recent pharmacokinetic study of rFVIIa in 10 non-bleeding hemophilia A and B patients who received a dose of 90 mg/kg rFVIIa, we noted that there were two divergent groups based on their laboratory response to rFVIIa. Study participants who achieved clot formation time determined by Hemodyne (FOT) or Rotational Thromboelastography (CT) < 15 min were noted to have a “rapid laboratory response”; conversely, those with a FOT and CT value ≥ 15 min were noted to have a “delayed laboratory response”. In order to determine whether the participants with a delayed laboratory response to rFVIIa 90 μ g/kg would have an improved response to higher doses of rFVIIa and to NN1731, additional blood samples were collected and spiked ex vivo. Patients and Methods: Blood samples from ten severe FVIII or FIX deficient patients were spiked with 1.28, 2.56, 3.84 μ g/mL rFVIIa (corresponding to 90, 180 and 270. Disclosures: Hedner: Novo Nordisk A/S: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Speakers Bureau. Ezban:Novo Nordisk A/S: Employment, Membership on an entity's Board of Directors or advisory committees, Research Funding.