What role for avacopan in the treatment of ANCA-associated vasculitis?

Recent experimental data have revealed the complement, and more specifically the C5a compound, plays a major role in the pathophysiology of ANCA associated vasculitis (AAV). The development of avacopan, an oral inhibitor of C5a receptor, has allowed to test the blockade of this immunological pathway, initially in a murine animal model of the disease, followed by a preliminary, phase 2 therapeutic trial in human disease, with promising results. An international phase 3 trial published in 2021 demonstrated that avacopan can be used instead of corticosteroids for the induction therapy of AAV, in association with an immunosuppressive drug such as cyclophosphamide or rituximab. The adjunction of this new-generation immunosuppressive drug does not increase the infectious risk, but seems to amplify the improvement of renal function during the initial treatment of renal vasculitis. These results have led to the recent registration of avacopan, opening new therapeutic options in AAV. (c) 2022 Published by Elsevier Masson SAS on behalf of Societe francophone de nephrologie, dialyse et transplantation.