In a recent press release, the FDA announced the acceptance of the New Drug Application (NDA) for avacopan, which is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action in the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and other complement-driven autoimmune and inflammatory diseases. ANCA-associated vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. As a result, organ damage and failure, especially involving the kidneys, manifests and is fatal if not treated. 

Currently available therapy for the treatment for ANCA-associated vasculitis involves courses of nonspecific immunosuppressants (cyclophosphamide or rituximab), combined with daily glucocorticoids for extended periods of time, which can be linked with substantial clinical risk, including death from infection.

In its NDA acceptance letter, the FDA also indicated that it may hold an advisory committee meeting to discuss the application per guidelines for new molecular entities. The NDA was submitted based on data from the global, phase III ADVOCATE trial, which is a randomized, double-blind, active-controlled, double-dummy phase III trial of 331 patients with ANCA-associated vasculitis in 20 countries to evaluate the efficacy and safety of avacopan. In the trial, qualified study subjects were randomized to receive avacopan plus either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) or prednisone plus either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate). 

Findings from the study demonstrated that 72.3% of avacopan-treated patients achieved disease remission (assessed by Birmingham Vasculitis Activity Score) at Week 26 compared with 70.1% of prednisone-treated patients, establishing noninferiority of the investigational treatment (P <.0001). At Week 52, avacopan demonstrated statistical superiority in sustained remission compared with prednisone (65.7% vs. 54.9%, respectively; P = .0066). In the trial, the avacopan group also demonstrated considerably lower glucocorticoid toxicity, better improvement in kidney function, and greater improvement in health-related quality of life measures compared with the prednisone group. 

Finally, avacopan demonstrated favorable safety results, with fewer patients having serious adverse events in the avacopan group than in the prednisone group. The Prescription Drug User Fee Act goal date for the avacopan NDA is projected for July 7, 2021.

Additionally, in the aforementioned press release, the manufacturer noted that it is also developing avacopan for the treatment of patients with C3 glomerulopathy (C3G) and hidradenitis suppurativa. The FDA has granted avacopan orphan drug designation for ANCA-associated vasculitis and C3G.
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