Complement Factor B

Class

Oral small-molecule complement inhibitor

Pathway

Alternative complement pathway (inhibits Factor B, blocking formation of the alternative pathway C3 convertase)

Complement Factor B is a plasma protein central to the alternative pathway of the complement system, an arm of innate immunity that tags pathogens and damaged cells for destruction and drives inflammation. Unlike the classical and lectin pathways, which require specific triggers such as antibodies, the alternative pathway is continuously active at a low level and also serves as an amplification loop that intensifies complement activation regardless of how it began. Factor B is cleaved to form the enzyme complex that generates C3b, the central molecule that opsonizes targets and fuels further complement activation and eventual formation of the membrane attack complex, which can lyse cells. When this amplification loop is dysregulated, it can damage the body's own cells and tissues, as occurs in conditions such as paroxysmal nocturnal hemoglobinuria, C3 glomerulopathy, and other complement-mediated kidney and blood disorders. Inhibiting Factor B interrupts formation of the alternative pathway's convertase, dampening this amplification loop and reducing downstream tissue injury and cell destruction. Because the alternative pathway also reinforces complement activity initiated through the other two pathways, targeting it upstream can broadly attenuate complement-driven pathology across multiple disease contexts, making Factor B inhibition a mechanistically distinct alternative to therapies that act further downstream in the cascade.