The FDA approval of pegcetacoplan (Empaveli), a PEGylated compstatin-based C3 
therapeutic, as a new treatment for paroxysmal nocturnal hemoglobinuria (PNH) 
marks a milestone in the history of complement drug discovery. Almost 15 years 
after the approval of the first complement-specific drug for PNH, the anti-C5 
antibody eculizumab, a novel class of complement inhibitors with a distinct 
mechanism of action finally enters the clinic. This landmark decision broadens 
the spectrum of available complement therapeutics, offering patients with unmet 
clinical needs or insufficient responses to anti-C5 therapy an alternative 
treatment option with a broad activity profile. Here we present a brief 
historical account of this newly approved complement drug, consolidating its 
approval within the long research record of the compstatin family of peptidic C3 
inhibitors.