Kidney Week

Abstract: SU-OR32

Complement C5a Receptor Inhibitor Avacopan Improves Renal Function in ANCA Vasculitis

Session Information

• Halfway Through the Marathon: Clinical Candidates in Development
  October 25, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Jayne, David R.W., Addenbrooke's Hospital, Cambridge, Cambridgeshire, United Kingdom

David R.W. Jayne, MD, MBChB



David Jayne is Professor of Clinical Autoimmunity at the University of Cambridge, UK, and Director of the Vasculitis and Lupus service at Addenbrookes Hospital Cambridge. He trained at the Universities of Cambridge and London, and in nephrology at Harvard Medical School, Boston, USA. He was a research fellow at Imperial College London and the University of Cambridge and was appointed as a Senior Lecturer in Nephrology at St George’s Hospital London. He is a co-founder and the current President of the European Vasculitis Society and his research focus has been ANCA vasculitis, having led a sequence of International randomised controlled trials over the last 25 years. His research group conducts first into disease trials of newer immunosuppressives and biologics in vasculitis and lupus. He has published over 400 peer reviewed papers and has contributed to numerous guideline statements. The clinical service in Cambridge cares for over 2000 patients with complex multi-system autoimmunity and receives tertiary referrals from throughout the UK and beyond.

• Merkel, Peter A., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Peter A. Merkel,

• Yue, Huibin, ChemoCentryx Inc, Mountain View, California, United States

Huibin Yue,

• Kelleher, Catherine L., ChemoCentryx Inc, Mountain View, California, United States

Catherine L. Kelleher,

• Schall, Thomas J., ChemoCentryx Inc, Mountain View, California, United States

Thomas J. Schall,

• Bekker, Pirow, ChemoCentryx Inc, Mountain View, California, United States

Pirow Bekker,

Background

Renal impairment is common in anti-neutrophil cytoplasmic autoantibody-associated vasculitis. The resulting chronic kidney disease and exacerbation of the toxicity risks of high dose or prolonged glucocorticoid use, a mainstay of ANCA treatment, are major consequences. Avacopan was tested for efficacy and effects on renal function compared to standard prednisone therapy in a randomized double-blind Phase 3 trial in ANCA vasculitis.

Methods

Subjects randomized 1:1 received either prednisone (60 mg tapered to 0 over 20 weeks) or avacopan (30 mg twice daily for 52 weeks), combined with either cyclophosphamide (CYC) followed by azathioprine, or rituximab (RTX). Primary endpoints: Disease remission at week 26 and sustained remission at week 52. Changes in urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were also assessed.

Results

330 subjects were treated: 166 to avacopan and 164 to prednisone treatment groups. Avacopan remission at week 26 was 72.3% vs. 70.1%, for prednisone (P<0.0001 for non-inferiority); avacopan was superior to prednisone for sustained remission (week 52, 65.7%, avacopan vs. 54.9%, prednisone, P=0.0066).
81% percent of subjects had renal disease. UACR decreased more rapidly with avacopan than prednisone: week 4 avacopan was 40% below baseline vs. no change for prednisone (P<0.0001). Baseline to week 52 eGFR (mL/min/1.73 m²) improvement: avacopan eGFR +7.3 vs. prednisone +4.1 (P=0.029). In subjects with baseline eGFR <30: mean eGFR improved 67% more with avacopan than prednisone to week 52: avacopan eGFR +13.7 vs. prednisone +8.2 (P=0.01).

Conclusion

Treatment with avacopan for ANCA vasculitis compared with standard glucocorticoid therapy (both combined with either CYC or RTX) is as effective for remission induction at 26 weeks, and superior to prednisone for sustained remission after 52 weeks. Avacopan led to faster falls in UACR and greater recovery in eGFR when compared to standard prednisone therapy. These findings have important implications for the long term health of AAV patients through better overall disease control, reduced prednisone exposure and reduced severity of chronic kidney disease.

Funding

• Commercial Support – ChemoCentryx