Adakveo

Crizanlizumab is a selective immunoglobulin G2 (IgG2) kappa humanised monoclonal antibody (mAb) that binds to P-selectin with high affinity and blocks the interaction with its ligands including P-selectin glycoprotein ligand 1 (PSGL-1). Crizanlizumab can also dissociate preformed P-selectin/PSGL-1 complex. P-selectin is an adhesion molecule expressed on activated endothelial cells and platelets. It plays an essential role in the initial recruitment of leukocytes and the aggregation of platelets to the site of vascular injury during inflammation.In the chronic pro-inflammatory state associated with sickle cell disease, P-selectin is over-expressed and circulating blood cells and the endothelium are activated and become hyperadhesive. P-selectin mediated multi-cellular adhesion is a key factor in the pathogenesis of vaso-occlusion and vasoocclusive crises. Elevated levels of P-selectin are found in patients with sickle cell disease.Binding P-selectin on the surface of the activated endothelium and platelets has been shown to effectively block interactions between endothelial cells, platelets, red blood cells, and leukocytes, thereby preventing vaso-occlusion.