Avacopan for the treatment of ANCA-associated vasculitis

ABSTRACT

Introduction: Anti-neutrophil cytoplasm autoantibodies (ANCA)-associated vasculitides (AAVs) are a group of rare heterogeneous diseases characterized by blood vessel inflammation resulting in organ destruction and death. Although various treatment strategies have resulted in marked improvement in vasculitis-specific outcomes, many patients with AAV continue to suffer from complications related to the prolonged use of glucocorticoids (GC) such as infections, metabolic abnormalities, and increased cardiovascular morbidity. Recently, activation of the alternative complement pathway has been implicated in the augmentation of the damage caused by AAV via the complement C5a receptor (C5aR1, CD88). Specifically targeting this pathway may lead to improved outcomes in patients with AAV.

Areas covered: In this article, we have summarized the rationale for targeting the complement pathway in AAV. The relevant pre-clinical, phase I, II and III findings with emphasis on the efficacy, and safety of avacopan, a new oral competitive inhibitor that interferes with the binding of C5a to C5aR1 (CD88), are reviewed.

Expert opinion: These results are encouraging, may led to major changes in the treatment approach for AAV, and give rise to future studies utilizing complement inhibitors in AAV patients, and potentially in other immune mediated diseases.

KEYWORDS:

• ANCA
• avacopan
• complement
• glucocorticoids
• vasculitis

Article highlights

• Synopsis of how the different complement pathways play a role in the pathogenesis of ANCA-associated vasculitis and cardiovascular diseases.

• Discussion of avacopan’s mechanisms of action and pharmacology.

• Summary of pre-clinical, phase I, II and III data related to the efficacy and safety of avacopan in ANCA-associated vasculitis.

• Avacopan is one the first agents to achieve that key goal for the treatment of ANCA-associated to reduce glucocorticoids exposure and toxicity.

Declaration of interest

CP reports receiving in the past 2 years fees for serving on advisory boards from ChemoCentryx, GlaxoSmithKline, Astra-Zeneca and Hoffman-LaRoche; he also reports lecture fees and research/educational grant support from Hoffman-LaRoche, Pfizer and GlaxoSmithKline. JWCT reports serving as the chair of the IDMC for InflaRx; he also reports lecture fees from Sanofi and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This article was not funded.