Abstract Number: PB0859
Meeting: ISTH 2020 Congress
Background: Recombinant factor VIIa (NovoSeven®, NovoNordisk, Bagsvaerd, Denmark) is used in the management of bleeding in patients with hemophilia. A generic version of NovoSeven® is also developed for the same indication (AryoSeven, AryoGen, Tehran, Iran).
Aims: The purpose of this study was to compare several batches of generic of rFVIIa, namely AryoSeven, with multiple commercially available batches of branded NovoSeven® to determine biosimilarity.
Methods: Four commercially available lots of Novoseven® were obtained through US and European sources and compared to 6 clinical batches of AryoSeven. Samples were profiled in vitro using surface enhanced laser desorption ionization (SELDI) mass spectrometry, gel electrophoresis (GE), immunoblotting studies, and procoagulant activity as measured by a clot based method. Thrombin generation studies were carried out using NHP supplemented with 0-1.0 ug/ml rFVIIa. The pharmacokinetic profiles representative batch each of the NovoSeven® and AryoSeven were studied in primates after a 50 ug/kg bolus IV.
Results: The molecular profiles, GE and immunoblotting studies of the two groups of agents showed a comparable profile with identical sharp peaks at 50 kDa and 29 kDa. In the clot based functional assays performed using citrated whole blood and retrieved plasma, the two FVIIa products produced comparable procoagulant effects in the PT and aPTT assays In the primate pharmacokinetic studies at a dose of 50 ug/kg, both groups exhibited similar pharmacokinetic profiles in terms of biologic half-life, Cmax, volume of distribution and other parameters.
Conclusions: The pharmacokinetic profile of the NovoSeven® and AryoSeven as studied in primates by measuring the factor VIIa level for up to 4 hours post-administration were found to be comparable. These results support the hypothesis that NovoSeven® and AryoSeven are biosimilar. Further clinical validation studies are warranted.
To cite this abstract in AMA style:Iacobelli M, Sadeghi N, Kouta A, Duff R, Iqbal O, Hoppensteadt D, Jeske W, Walenga J, Fareed J. A Generic Recombinant Factor VIIa Is Comparable to the Branded Novoseven in In-vitro and Pharmacokinetic Studies in Primates [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-generic-recombinant-factor-viia-is-comparable-to-the-branded-novoseven-in-in-vitro-and-pharmacokinetic-studies-in-primates/. Accessed October 26, 2020.
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