Abstract: TH-PO0714
Biomarker Insights from the Phase 3 APPLAUSE-IgAN Study: Iptacopan's Proteomic Signature in IgAN
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Barratt, Jonathan, The Mayer IgA Nephropathy Laboratories, University of Leicester, Leicester, United Kingdom
- Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia
- Sprangers, Ben, Department of Nephrology, Ziekenhuis Oost Limburg, Genk, Belgium
- Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Kashihara, Naoki, Kawasaki Medical School, Okayama, Japan
- Maes, Bart D., AZ Delta, Roeselare, Belgium
- Zhang, Hong, Peking University First Hospital, Beijing, China
- Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina
- Grioni, Andrea, Novartis Institutes for BioMedical Research Basel, Basel, Switzerland
- Applegate, Douglas, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, United States
- Hach, Thomas, Novartis Pharma AG, Basel, Switzerland
- Merkel, Tobias, Novartis Pharma AG, Basel, Switzerland
- Desai, Manasi Mital, Novartis Pharmaceuticals Limited, London, United Kingdom
- Renfurm, Ronny, Novartis Pharma AG, Basel, Switzerland
- Rizk, Dana V., University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Iptacopan, a complement factor B inhibitor, significantly reduced proteinuria in the Phase III APPLAUSE-IgAN trial (NCT04578834), leading to its accelerated approval by the US FDA for the treatment of primary IgAN. This exploratory APPLAUSE-IgAN biomarker substudy aimed to expand on an iptacopan proteomic signature from a Phase II trial (NCT03373461).
Methods
SomaScan 4.1, a highly multiplexed, semiquantitative, aptamer-based proteomics technology that simultaneously quantified ~6500 proteins, profiled the plasma proteome in baseline and Month 9 APPLAUSE-IgAN samples. We used R package limma to identify protein concentration changes between placebo and iptacopan at Month 9 (statistical significance: false discovery rate <0.01, absolute log fold change >0.5). Pathway enrichment analysis used R package clusterProfiler.
Results
SomaScan analysis from randomly selected patients in the APPLAUSE-IgAN biomarker substudy (N=58) identified 299 proteins modulated by iptacopan, which were mostly downregulated at Month 9 (Figure A). The data confirmed 79/81 proteins from the Phase II proteomic signature. Pathway enrichment analysis associated the modulated proteins with several proposed IgAN-related biological processes, including leukocyte proliferation and migration, and inflammatory response (Figure B).
Conclusion
These data expand iptacopan’s previously reported Phase II proteomic signature and suggest that alternative complement pathway inhibition downregulates several IgAN-related biological processes. Biomarker analyses to be conducted at completion of APPLAUSE-IgAN and an ongoing kidney biopsy study (NCT06797518) will help to further characterize mechanistic aspects of alternative complement pathway inhibition in IgAN.
Funding
- Commercial Support – Novartis