Phase 3 results ADVOCATE C5a receptor inhibition for ANCA-associated vasculitis
medwireNews: Findings from the ADVOCATE trial suggest that patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who are treated with avacopan are more likely to experience sustained remission than those given glucocorticoids.
Speaking at the EULAR 2020 E-Congress, Peter Merkel (University of Pennsylvania, Philadelphia, USA) explained that avacopan (CCX168) is a “highly selective” antagonist of the complement fragment C5a, a molecule known to be linked to the pathogenesis of ANCA-associated vasculitis.
The rate of remission at week 26 – defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and no glucocorticoid treatment within the past 4 weeks – was 72.3% for the 166 participants who were randomly assigned to receive avacopan 30 mg twice daily alongside prednisone placebo and standard treatment with rituximab or cyclophosphamide followed by azathioprine. By comparison, the rate of remission was 70.1% for the 164 participants who were instead given prednisone at a dose of 60 mg/day tapered to zero over 20 weeks alongside avacopan placebo and standard therapy.
“This was very clearly within the margins for noninferiority and the primary outcome was met,” said Merkel.
Moreover, avacopan was superior to prednisone for the coprimary endpoint of sustained remission, he added, with 65.7% versus 54.9% of patients in the avacopan and control groups, respectively, remaining in remission at the 1-year follow-up.
The ADVOCATE investigators also demonstrated less glucocorticoid-related toxicity and a steroid-sparing effect among avacopan-treated patients. The average glucocorticoid toxicity index worsening score was 39.7% in the avacopan arm versus 56.6% in the control group at week 26, and patients given avacopan had lower average weekly glucocorticoid use over time.
Merkel said that avacopan had a “very acceptable safety profile” in the trial, with “no important safety signals.” A total of 42.2% of patients in the avacopan group and 45.1% of those given prednisone experienced serious adverse events (AEs). Serious infections were reported in 13.3% and 15.2% of patients, respectively, and a corresponding 66.3% and 80.5% had AEs judged by the investigators to be potentially related to glucocorticoids.
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