Abstract: SA-PO0723
Proteomic Profiling of 24-Hour Urine in the Phase 2 IgAN SANCTUARY Trial
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Roth, Samuel J, Bioinformatics, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Cammett, Tobin J., Translational Research, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Li, Ming, Translational Research, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Nolan, Stephen, Clinical Development, Alexion, AstraZeneca Rare Disease, Dublin, Ireland
- Williams, Cory, Clinical Development, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Farag, Youssef MK, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Kateifides, Andreas, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Lambden, Simon, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- Singh, Ajay K., Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Ricchiuto, Piero, Bioinformatics, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
Background
In IgA nephropathy (IgAN), immune complex deposition and complement activation lead to kidney damage. Ravulizumab (RAV), a complement C5 inhibitor, led to rapid and clinically meaningful proteinuria reduction in a ph2 randomized controlled trial (NCT04564339; JASN 36(4):645-656). Traditional biomarkers provide evidence of complement involvement in IgAN; urine proteomic analysis may provide further insight into the pathophysiology of IgAN and mechanism of action of RAV.
Methods
This analysis included 54 patients with IgAN in SANCTUARY (pts) and 20 age-, sex-, and ethnicity-matched healthy normal donors (ND). 24-hour urine samples were collected at baseline and week (wk) 26 for proteomic analysis. The Olink platform was used to investigate a panel of >2900 proteins in pts at baseline vs ND and in pts treated with RAV (n=32) vs PBO (n=22) for 26 wks. A bespoke analytical workflow including differential expression analysis and machine learning was used.
Results
The proteomic profile demonstrated the ability to differentiate RAV vs PBO-treated pts using a distinctive set of biomarkers (Figure 1). Select proteins were upregulated in pts with IgAN vs ND, of which 27 were downregulated with RAV vs PBO (Figure 2). These 27 proteins included complement pathway proteins and will be assessed further for biological validation as potential biomarkers.
Conclusion
This analysis provides key insights into IgAN pathophysiology and the mechanism of action of RAV. Further exploration of the IgAN proteome could enhance our understanding of IgAN and inform future therapeutic approaches.
Funding
- Commercial Support – Alexion, AstraZeneca Rare Disease, Boston, MA, United States