FDA accepts avacopan NDA for ANCA-associated vasculitis

David A. McLain, MD, FACP, FACR

In the evolution of treatment of ANCA-associated vasculitis, we have seen great strides over the past 50 years. In the early 1970s, Anthony Fauci, MD, and his colleagues at the NIH, developed a protocol that used a 3-to-6-month course of daily cyclophosphamide plus steroids, followed by long-term daily azathioprine (AZA) plus steroids in the treatment of AAV. More than 90% of individuals with this once 80% fatal disease experienced remission after they received cyclophosphamide-based therapy. However, an unmet need of this therapy were relapses with the need for retreatment.

Then in 2010, John Stone, MD, MPH, and Ulrich Specks, MD, were able to show that rituximab provided comparable benefits as standard therapy for ANCA-associated vasculitis using rituximab once a week for one month, plus steroids versus 3 to 6 months of daily cyclophosphamide therapy plus steroids, followed by daily AZA. This new approach proved its superiority in preventing relapse with rituximab vs. standard of care.

Now, in 2020, there appears another new addition to the treatment of AAV. Avacopan has been shown in the ADVOCATE trial to be statistically superior in sustaining remission at 52 weeks compared to the prednisone group. In the trial, the avacopan group also showed greater improvement in kidney function, significantly lower glucocorticoid toxicity, and greater improvement in health-related QoL measures compared to the prednisone group; there were also fewer adverse drug reactions in the avacopan group. It looks like we will have another medication option to use in AAV that appears to improve outcomes.