Avacopan, a selective C5a receptor antagonist, for anti-neutrophil cytoplasmic antibody-associated vasculitis

Avacopan, an orally administered C5a receptor antagonist, has been approved for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan and the USA. In ADVOCATE Phase III clinical trial, patients with active MPA or GPA received either 30 mg avacopan twice daily or prednisone on a tapering schedule in combination with rituximab or cyclophosphamide (followed by azathioprine). The trial met its two primary endpoints: avacopan showed non-inferiority to prednisone for achieving remission at Week 26 (avacopan, 72.3%; prednisone, 70.1%; p < .001 for non-inferiority and p = .24 for superiority) and superiority for maintaining remission at Week 52 (65.7% for avacopan, 54.9% prednisone, p < .001 for non-inferiority and p = .007 for superiority). Of several key secondary endpoints tested, the glucocorticoid toxicity index (GTI)-cumulative worsening score and GTI-aggregate improvement score were significantly lower in the avacopan group than in the prednisone group at both Weeks 26 and 52. Serious adverse events related and unrelated to the worsening vasculitis were reported at 10.2% and 37.3% in the avacopan group and at 14.0% and 39.0% in the prednisone group, respectively. Avacopan has set the stage for the semi-glucocorticoid-free or glucocorticoid-free treatment of MPA and GPA.