Safety of Avacopan for the Treatment of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Combined Data From Three Clinical Trials

Abstract

Objective: This study aimed to report the safety of avacopan, an oral selective complement C5a receptor antagonist, using pooled data from clinical trials in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (granulomatosis with polyangiitis [GPA] or microscopic polyangiitis [MPA]). Methods: Data were included from two phase 2 (CLEAR [NCT01363388] and CLASSIC [NCT02222155]) and one phase 3 (ADVOCATE [NCT02994927]) double-blind randomized controlled trials comparing the safety and efficacy of avacopan with active non-avacopan control regimens to induce remission in patients with GPA or MPA. In CLEAR and ADVOCATE, avacopan-treated patients received either no or lower doses of study-supplied prednisone than the control groups; in CLASSIC, all groups received the same dose of study-supplied prednisone. Assessments included rates of exposure-adjusted adverse events (AEs), serious AEs (SAEs), and AEs of special interest. Results: Overall, 439 patients with GPA or MPA (avacopan: n = 239; non-avacopan: n = 200) were included. The exposure-adjusted rates of AEs, SAEs, white blood cell (WBC) count reductions, and infections were lower with avacopan versus control (between-group differences in rate per 100 patient-years −151.9 [95% confidence interval (CI) −218.6 to −85.3], −20.8 [95% CI −38.3 to −3.3], −11.6 [95% CI −22.2 to −1.2], and −24.3 [95% CI −48.5 to −0.1], respectively). SAEs associated with hepatic function abnormalities occurred in 4.4% of the avacopan group and 2.8% of the control group. Conclusion: In clinical trials of GPA or MPA, use of avacopan was associated with fewer AEs, SAEs, and WBC count reductions and fewer infections than non-avacopan treatment. Safety data support the use of avacopan in patients with GPA or MPA.