Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates.
作者： R. Stidl , S. Fuchs , M. Bossard , J. Siekmann , P. L. Turecek
DOI: 10.1111/HAE.12762
关键词:
摘要: Introduction BAX 855 is a PEGylated human full-length recombinant factor VIII (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has been optimized to retain functionality of the FVIII molecule, improve its pharmacokinetic properties and allow less frequent injections while maintaining efficacy. Aim The aim this study was confirm that excellent safety profile ADVATE remains unchanged after PEGylation. Methods Non-clinical studies with BAX respective unbound polyethylene glycol (PEG) were conducted in several species. distribution single dose radiolabelled further investigated rats. Publically available data PEG alone biomolecules summarized reviewed for specific findings attributable or biopharmaceuticals. Results Safety pharmacology rabbits macaques repeated toxicity rats identified no issues. Results administered showed radioactivity completely excreted; urine major elimination route. A 28-day dosed constituent (PEG2ru20KCOOH) adverse non-adverse effects. Safety PEG-protein conjugates indicate concerns associated at clinically relevant levels. Although vacuolation certain cell types reported mammals, such observed constituent. Conclusion Non-clinical evaluation signals; compound now clinical development treatment patients haemophilia A.
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