Compstatins: the dawn of clinical C3-targeted complement inhibition.

Despite the growing recognition of the complement system as a major contributor to a variety of clinical conditions, the therapeutic arsenal has remained scarce. The introduction of an anti-C5 antibody in 2007 raised confidence in complement-targeted therapy. However, it became apparent that inhibition of late-stage effector generation might not be sufficient in multifactorial complement disorders. Upstream intervention at the level of C3 activation has therefore been considered promising. The approval of pegcetacoplan, a C3 inhibitor of the compstatin family, in 2021 served as critical validation of C3-targeted treatment. This review delineates the evolution of the compstatin family from its academic origins to the clinic and highlights current and potential future applications of this promising drug class in complement diseases.

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Déclaration de conflit d'intérêts

Declaration of interests J.D.L. is the founder of Amyndas Pharmaceuticals, which is developing complement inhibitors for therapeutic purposes; is the inventor of patents or patent applications that describe the use of complement inhibitors for therapeutic purposes, some of which are being developed by Amyndas Pharmaceuticals; is the inventor of the compstatin technology licensed to Apellis Pharmaceuticals (Cp05/POT-4/APL-1 and PEGylated derivatives such as APL-2/pegcetacoplan and APL-9); and has provided paid consulting services to Achillion, Ra Pharma, Viropharma, Sanofi, Shire, LipimetiX, and Baxter. D.R. is the inventor of patents or patent applications that describe complement inhibitors for therapeutic purposes, some of which are developed by Amyndas Pharmaceuticals; has provided paid consulting services to Roche Pharma, Sobi, and Greenovation; and has provided scientific lectures sponsored by Roche and Alexion. The other authors claim no conflict of interest.