Safety and Efficacy of Investigational Single-Chain Recombinant Factor VIII Examined in Preclinical Studies
- By BSTQ Staff
A recombinant factor VIII (rFVIII) featuring a covalent linkage between heavy and light chains and expressed as a single chain molecule has demonstrated “convincing hemostatic efficacy and excellent tolerability” in multiple animal studies, according to CSL Behring researchers. Called “rVIIISingleChain” (CSL627), this investigational product was designed with the goal of enhancing the pharmacokinetic profile of rFVIII and its binding affinity to von Willebrand factor.
In a tail-clip bleeding model in which observers were blinded, hemophilia A mice were injected with escalating doses (1 to 150 IU/kg) of rVIII-SingleChain, B-domain deleted rFVIII (ReFacto AF) or full-length rFVIII products (Advate, Helixate). Total blood loss and the percentage of animals in which hemostasis occurred were indistinguishable across products. In a thrombosis model, the effect of rVIII-SingleChain on the incidence of thrombus formation was nonsignificant and comparable to B-domain deleted rFVIII at doses up to 500 IU/kg.
In safety and toxicity studies, treatment with rVIIISingleChain was not associated with anaphylactic reaction or local intolerance, and demonstrated “an excellent overall safety profile.” The investigators called for continued investigation of the product in human Phase I/III trials.
