Adakveo: animal efficacy model or human cells?

“The published in vitro data demonstrate that crizanlizumab blocks binding of human P-selectin to its ligand PSG-1, blocks neutrophil binding to P-selectin, blocks leukocyte rolling and adhesion to human vascular endothelium under shear stress, inhibits interaction of neutrophils with stimulated platelets, and blocks binding of human sickled red cells to human endothelium under flow.”

“Primary pharmacodynamics was only studied ex vivo with SelG1 and SEG101 because of occurrence of immunological reactions and species differences in target recognition of P-selectin, which hamper animal PD studies.”

“Taken together, the primary pharmacology evaluation of SEG101 (crizanlizumab) lacks firm in vitro documentation, leaving some uncertainty on specificity and off-target activity. However, the supportive functional data generated with the parental antibody SelG1 provide sufficient support for the rationale for crizanlizumab´s biological activity in the prevention of vaso-occlusive crises.”