avacopan

Avacopan is an oral small-molecule medication that functions as a selective antagonist of the C5a receptor (C5aR1). By blocking C5a signaling, it reduces neutrophil activation and the inflammatory cascade driven by the complement system, offering an approach to treating inflammatory vasculitis without broad C5 depletion. It is approved for adults with ANCA-associated vasculitis (AAV), a group that includes granulomatosis with polyangiitis and microscopic polyangiitis.

Mechanism: C5aR1 antagonism inhibits neutrophil chemotaxis and activation at sites of vascular inflammation, limiting tissue injury while preserving upstream complement functions in host defense.

Clinical development and use: In the phase 3 ADVOCATE trial, avacopan demonstrated noninferiority to prednisone in achieving sustained remission at 52 weeks when used with standard-of-care therapy for adults with AAV, and it allowed reduced glucocorticoid exposure. These results supported its regulatory approval as a component of AAV treatment to replace or reduce long-term steroid use.

Regulatory status and availability: Avacopan was approved by the U.S. Food and Drug Administration in 2021 for adults with AAV, marketed under the brand Tavneos. Regional approvals vary.

Safety: Common adverse events reported in trials include infections, headaches, hypertension, and nausea. Elevations in liver enzymes were observed in some patients, necessitating routine monitoring and assessment of infectious risk during treatment.