Crovalimab (SKY59; RO7112689) is an Fc-engineered and pH-dependent humanised monoclonal antibody that binds to complement C5 and blocks its cleavage into C5a and C5b, thereby inhibiting MAC formation and intravascular haemolysis. It can rebind to the FcRn receptor under acidic pH conditions and return to the bloodstream, making it suitable for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).

Method:
In cynomolgus monkeys, the pharmacodynamic and pharmacokinetic profiles of a single intravenous dose of Crovalimab (20 mg/kg) and its IgG1 derivative SG115 were evaluated. A multiple dosing regimen (intravenous/subcutaneous) was also used to assess immunological and serological responses.

Result:
A single dose of Crovalimab inhibited plasma C5 accumulation and sustained complement suppression for up to 8 weeks. SG115 showed a slow clearance rate (1.87 mL/day/kg). The multiple-dose regimen led to increased hemolytic activity, dysphagia, and elevated LDH and ALT levels.[1]