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Abstract: SA-PO890

Targeted Release Formulation (TRF) Budesonide (Nefecon) Reduces Serum Biomarkers of Lymphocyte Activation in IgA Nephropathy, Which Correlates with Changes in Serum B Cell-Activating Factor (BAFF) Levels 

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Nawaz, Nadia, University of Leicester, Leicester, United Kingdom
  • Molyneux, Karen, University of Leicester, Leicester, United Kingdom
  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Group or Team Name

  • IgA Nephropathy Group.
Background

The targeted-release formulation of budesonide, Nefecon, is designed to deliver budesonide to the gut-associated lymphoid tissue of the terminal ileum, a major site of immunoglobulin A (IgA) production. In the phase 2b NEFIGAN trial, treatment with Nefecon significantly reduced serum levels of galactose-deficient IgA1IgA/IgG immune complexes and cytokines involved in B-cell activation. This study investigates the effect of Nefecon on biomarkers of lymphocyte activation in the Part A population of the phase 3 double-blind, randomized controlled NefIgArd trial in which 9 months’ treatment with Nefecon led to a reduction in proteinuria at 9 months (p=0.0005), and a reduction in loss of estimated glomerular filtration rate at 24 months (p<0.0001) compared with placebo.

Methods

Levels of the soluble cluster of differentiation (CD)23, CD27, and CD30 were measured using Luminex technology in 160 NefIgArd Part A participants using serum samples collected at baseline and 3, 6, and 9 months post randomization. Comparisons between placebo and Nefecon treated groups were made at each time point using unpaired t-tests, with a significance level of p<0.05.

Results

Treatment with Nefecon 16 mg/day resulted in a significant reduction in the levels of sCD23, sCD27, and sCD30 at 3 months (all p values <0.0001), 6 months (all p values <0.0001), and 9 months (all p values <0.0001), confirming the findings from the NEFIGAN trial. The extent of sCD23, sCD27, and sCD30 suppression correlated with the magnitude of B-cell activating factor (BAFF) reductions at each timepoint. sCD30 reductions at 6 months and 9 months correlated with the magnitude of reductions in IgA/IgG immune complexes.

Conclusion

These data validate the findings from the phase 2b study and further support a disease-modifying action of Nefecon, specifically an action on the BAFF-lymphocyte interactome and immune complex formation in immunoglobulin A nephropathy.

Funding

  • Commercial Support – Calliditas Therapeutics