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

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.