Ultomiris

Ravulizumab rch is a humanised monoclonal antibody (mAb) consisting of 2 identical 448 amino acid heavy chains and 2 identical 214 amino acid light chains and has a molecular weight of approximately 148kDa.Ravulizumab rch is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the pro-inflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9, also known as the membrane attack complex (MAC)]) and preventing the generation of the C5b-9 or MAC. By binding specifically to C5, ravulizumab rch antagonises terminal complement-mediated inflammation, cell activation, and cell lysis while preserving the early components of complement activation that are essential for opsonisation of microorganisms and clearance of immune complexes. This mechanism of action provides the therapeutic rationale for the use of Ultomiris in paroxysmal nocturnal haemoglobinuria (PNH), in which uncontrolled complement activation is involved. In patients with PNH, complement mediated intravascular haemolysis is blocked with Ultomiris treatment. Ravulizumab rch was specifically engineered to dissociate from C5 and associate with human neonatal Fc receptor (FcRn) at pH 6.0 (while minimising the impact in binding to C5 in intravascular space where the normal pH is 7.4). As a result, dissociation of antibody:C5 complexes in the acidified environment of the early endosome after pinocytosis is increased. Therefore, free antibody is recycled from the early endosome back into the vascular compartment by FcRn, resulting in an extended ravulizumab rch terminal elimination half-life.