Abstract: TH-OR043
Change in Soluble Biomarker Levels in Patients with IgAN: Analysis of the Phase 2 Trial of Ravulizumab (SANCTUARY)
Session Information
- Glomerular Precision Nephrology: Novel Mechanisms, Biomarkers, and Therapeutic Targets
November 06, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:30 PM - 05:40 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cammett, Tobin J., Translational Research, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Millman, Ellen E., Translational Research, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Luna, Julio Cesar, Translational Research, Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Rice, Kara, Biostatistics, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Garlo, Katherine, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Kateifides, Andreas, Clinical Development, 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
- Lafayette, Richard A., Stanford Glomerular Disease Center, Stanford University Medical Center, Stanford, California, United States
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- Farag, Youssef MK, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
Background
Complement activation plays an important role in the pathophysiology of IgA nephropathy (IgAN), leading to inflammation and progressive kidney damage. In a phase 2 trial, clinically meaningful proteinuria reduction was observed with the complement C5 inhibitor, ravulizumab (RAV).1 Here, we evaluated change over time in soluble biomarkers in patients (pts) treated with RAV vs placebo (PBO).
Methods
In SANCTUARY (NCT04564339), 66 adults with IgAN were randomized (2:1) to RAV (IV q8w) or placebo (PBO) for 26 weeks (wks). Spot urine was collected pre-dose on days 1, 15, 71, 127, and 183. Evaluable data were available from 60 pts. Validated immunoassays were performed on spot urine and soluble biomarker levels were normalized to urine creatinine (Cr). Longitudinal changes in biomarker levels were reported using descriptive statistics and a mixed model for repeated measures (MMRM) to compare RAV with PBO.
Results
With RAV, there was early (by Day 15), sustained, and marked reduction in sC5b-9/Cr and Ba/Cr (complement pathway products) (Figure). Sustained reduction in CD163/Cr (macrophage renal infiltration marker) was observed starting at day 71. MMRM analysis of change from baseline to wk26 showed significant reduction in sC5b-9/Cr, Ba/Cr, CD163/Cr, and KIM-1/Cr (proximal tubule injury marker) with RAV vs PBO (Figure).
Conclusion
In pts treated with RAV, there was an early and sustained reduction in biomarkers of complement activation and reduction in markers of macrophage renal infiltration and tubular injury. These results suggest reduced inflammation and kidney damage in response to C5 (terminal complement) inhibition and are consistent with the observed proteinuria reduction in SANCTUARY.1
1. Lafayette R, et al. J Am Soc Nephrol. 2025;36(4):645–656.
Funding
- Commercial Support – Alexion, AstraZeneca Rare Disease, Boston, MA, United States