Preliminary Assessment of Safety and Tolerability of Avacopan During the Early Access Program for ANCA-Associated Vasculitis.

Abstract

Introduction Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogeneous group of rare, life-threatening, systemic autoimmune disorders characterized by necrotizing vasculitis that predominantly affects the small bloodto medium-sized vessels. Patients with ANCA vasculitis experience side effects from immunosuppression used to achieve disease remission, notably from long-term use of glucocorticoids. Both a Phase 2 trial (CLEAR) and a Phase 3 pivotal trial (ADVOCATE) have demonstrated the potential for avacopan to reduce steroid use in patients with newly diagnosed or relapsing severe ANCA-associated vasculitis while maintaining efficacy and safety. Avacopan is an orally administered small-molecule C5a receptor (C5aR) antagonist that selectively blocks the effects of C5a through the C5aR, including blocking neutrophil chemoattraction and activation. Most recently, avacopan has been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of ANCAassociated vasculitis. In between the completion of the ADVOCATE study (2019) and the approval of regulatory agencies, 30 patients with a high unmet medical need have been treated with avacopan through the Early Access Program (EAP). Eligible for the EAP were patients with new or relapsing lifeor organ-threatening ANCA-associated vasculitis, requiring an induction treatment, who also had a high risk of steroid-related complications.