Pegcetacoplan (Empaveli™) is a PEGylated pentadecapeptide developed by Apellis 
Pharmaceuticals for the treatment of complement-mediated diseases. It binds to 
complement component 3 (C3) and its activation fragment C3b, controlling the 
cleavage of C3 and the generation of the downstream effectors of complement 
activation and thus both C3b-mediated extravascular haemolysis and terminal 
complement-mediated intravascular haemolysis. Pegcetacoplan is the first 
C3-targeted paroxysmal nocturnal haemoglobinuria (PNH) therapy to be approved 
(in May 2021) in the USA, where it is indicated for the treatment of adults with 
PNH, including those switching from C5 inhibitor therapy with eculizumab and 
ravulizumab. A regulatory assessment of pegcetacoplan for the treatment of PNH 
is currently underway in the EU and Australia. Pegcetacoplan is also being 
investigated as a therapeutic option in other complement-mediated diseases, 
including age-related macular degeneration, C3 glomerulopathy and autoimmune 
haemolytic anaemia. The recommended dosage regimen of pegcetacoplan is 1080 mg 
twice weekly, administered as a subcutaneous infusion via an infusion pump with 
a ≥ 20 mL reservoir. This article summarizes the milestones in the development 
of pegcetacoplan leading to this first approval for the treatment of adults with 
PNH.