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Research Article
20 November 2025

Matching-adjusted indirect comparison of kidney function in patients with immunoglobulin A nephropathy treated with nefecon or sparsentan

Authors: Christopher Ngai https://orcid.org/0000-0003-4136-1550, Mit Patel, Agnieszka Kopiec, Shuai Fu, and Noemi Hummel https://orcid.org/0009-0000-5656-5025 [email protected]Author Info & Affiliations
Volume 14, Number 12
https://doi.org/10.57264/cer-2025-0045
PDFFormats

Abstract

Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & methods: We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd (NCT03643965; n = 364), a randomized (1:1) trial of nefecon plus optimized renin–angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT (NCT03762850; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker. Mean absolute eGFR change and mean relative urine protein-to-creatinine and urine albumin-to-creatinine ratio changes from baseline at 9, 12 and 24 months (NefIgArd) or 36, 48 and 106 weeks (PROTECT) were analyzed using a mixed-effects model for repeated measures. A composite outcome (time to confirmed 40% eGFR reduction, end-stage kidney disease or all-cause mortality) was also included. An unanchored MAIC and network meta-analysis were used as sensitivity analyses. Results: The matching process reduced the effective sample for the NefIgArd trial from 364 to 208. Absolute eGFR change significantly favored nefecon over sparsentan at 9 months (mean difference, ml/min/1.73 m2 [95% credible interval]: 5.7 [3.1–8.2]), 12 months (3.5 [1.0–6.0]) and 24 months (3.3 [0.0–6.5]). Differences in other outcomes were generally not statistically significant. Sensitivity analysis results were consistent with the main findings. Conclusion: In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan.

Plain language summary

What is this article about?

Immunoglobulin A nephropathy (IgAN) is a progressive form of kidney disease that can lead to kidney failure in many patients over time. In recent years, different treatments have been approved for use in patients with IgAN, but no head-to-head comparisons of their effectiveness have been conducted. Nefecon is a targeted-release formulation of budesonide that targets the main underlying cause of IgAN in the gut. Sparsentan works downstream by reducing damage to the kidney. We carried out an anchored matching-adjusted indirect comparison of these new treatments using available data from their two pivotal phase III clinical trials (NefIgArd and PROTECT) to compare their effects on kidney function.

What were the results?

Nefecon on top of existing standard of care, was associated with less of a decline in estimated glomerular filtration rate (a measure of kidney function) at 9, 12 and 24 months than sparsentan. We carried out other similar analyses that supported this finding.

What do the results of the study mean?

The results suggest that nefecon is better at preserving kidney function than sparsentan. However, it is important to remember that they work in different ways and so potentially can be used as part of a wider strategy to prevent patients with IgAN from progressing to kidney failure.

Shareable abstract

This is a matching-adjusted indirect comparison of the efficacy profiles of two approved therapies (nefecon and sparsentan) for immunoglobulin A nephropathy using phase III clinical trial data. Nefecon (plus standard of care) preserved kidney function better than sparsentan.

Supplementary Material

File (supplementary materials.docx)

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
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