C5a

Where it comes from

Made in

Made when C5 convertase cuts C5, the last step before the membrane attack complex

Sent out by

Any complement activation: infection, sepsis, immune complexes, ischaemia and reperfusion

Acts on

• Neutrophils
• Monocytes and macrophages
• Endothelium
• Mast cells

What it does

• Draws neutrophils to a site and primes their burst of oxidants
• Makes vessels leak and endothelium sticky
• In sepsis, too much of it paralyses neutrophils and damages organs

In medicine

• Avacopan, a C5aR1 blocker, has been approved in the United States since 2021 as an add-on treatment for ANCA-associated vasculitis; it lowers how much steroid a patient needs but does not replace it ¹
• The journal that published avacopan’s pivotal trial retracted that report in June 2026; the approval has not changed ²
• Vilobelimab, an antibody against C5a itself, had a United States emergency authorisation in 2023 for ventilated COVID-19 patients and was authorised in the European Union in January 2025 under exceptional circumstances, although its phase 3 trial missed significance on survival ³
• Eculizumab and ravulizumab block C5 upstream, so C5a is never made: they treat paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, myasthenia gravis and neuromyelitis optica ⁴

Beyond the body’s own use

• Vilobelimab was also tried in early severe sepsis and in hidradenitis suppurativa, and C5a blockade in pyoderma gangrenosum; of all of those, only the COVID-19 trial led to an authorisation ³
• C5a promotes tumour growth in several animal models, and C5aR1 blockers are in early cancer work; nothing is established in people