Abstract: SA-PO0680
Targeting the Gut-Kidney Axis: Mediation Analysis of Immunological Biomarkers and Kidney Function Benefit with Nefecon in IgAN
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Barratt, Jonathan, College of Life Sciences, University of Leicester, Leicester, United Kingdom
- Jama, Amal A A, College of Life Sciences, University of Leicester, Leicester, United Kingdom
- Jones, Russell, Calliditas Therapeutics AB, Stockholm, Sweden
- Nawaz, Nadia, College of Life Sciences, University of Leicester, Leicester, United Kingdom
- Thomas, Roisin Clare, College of Life Sciences, University of Leicester, Leicester, United Kingdom
Background
Dysregulated immunoglobulin A (IgA) production in the gut is a key driver of IgA nephropathy (IgAN) pathogenesis. Nefecon, a targeted-release budesonide formulation, stabilizes kidney function, reduces proteinuria, and modulates immune biomarkers in IgAN. However, the relationship between specific immune changes and clinical benefit remains unclear. We evaluated whether stabilization of estimated glomerular filtration rate (eGFR) with nefecon is mediated by immune biomarkers.
Methods
The Phase 3 NefIgArd trial compared treatment with nefecon versus placebo for 9 months followed by 15 months off treatment in adults with IgAN (Lafayette RA, et al. Lancet 2023;402:859-870). Primary endpoints included time-weighted average eGFR over 2 years. eGFR and biomarkers were evaluated at baseline and at prespecified visits during treatment (including Month 9) and follow-up. Associations between treatment, biomarker changes, and eGFR were analyzed using robust regression with multiple imputation methods and with mediation analyses.
Results
Seven of 30 biomarkers were shown to mediate eGFR stabilization versus placebo during the 9-month treatment period: Gd-IgA1, BAFF, CCL19, soluble (s)CD23, sCD27, sCD30, and IL18BPA (Fig). Mediation analyses indicated that the effect of nefecon on eGFR was partially attributable to pathways involving these biomarkers, while additional mechanisms independent of these mediators also contributed.
Conclusion
At 9 months, biomarker changes indicated lymphocyte and IgA-related pathway activations with nefecon that were associated with stabilization of kidney function. These findings suggest a mechanistic relationship between gut-targeted immunomodulation and clinical benefit in IgAN and support a disease-modifying effect of nefecon.
Acknowledgment
This trial was funded by Calliditas Therapeutics AB, an Asahi Kasei company. Medical writing assistance was provided by Fraser Collins, PhD, of OHMC, London, UK, with financial support from Calliditas Therapeutics AB and in accordance with the 2022 Good Publication Practice guidelines (https://www.ismpp.org/gpp-2022).
Funding
- Commercial Support – Calliditas Therapeutics AB (an Asahi Kasei company)