Innovation in IgAN: Exploring New Therapies and Combination Approaches, With Brendon Neuen, MBBS, PhD

The therapeutic landscape for IgA nephropathy (IgAN) is evolving at an unprecedented pace. Multiple new therapies are now available and others are progressing through clinical development, raising critical questions about how to best use these treatments in practice.

In the past few years, the US Food and Drug Administration (FDA) has granted accelerated approval to Novartis’ iptacopan (Fabhalta) and atrasentan (Vanrafia) as well as full approval to Travere Therapeutics’ sparsentan (Filspari) and Calliditas Therapeutics’ budesonide (Tarpeyo) delayed release capsules.1,2,3

“Therapeutic options for IgA nephropathy have expanded so rapidly in the last few years, and we now have multiple agents approved by regulatory agencies like the US FDA to reduce proteinuria and reduce kidney function decline,” Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and director of the Kidney Trials Unit with Royal North Shore Hospital, told HCPLive. “The question that is being asked by clinicians now and is increasingly relevant, is how do we use these drugs? Which ones should we preferentially use, and can we use them in combination?"

To clarify how available treatments compare, Neuen and a team of investigators conducted a systematic review and meta-analysis in which they pooled phase 2 and phase 3 trial data for nonimmunosuppressive antiproteinuric therapies, corticosteroids, B-cell modulating agents, and complement inhibitors. Treatment effects on proteinuria and eGFR slope were pooled overall and by drug class.4

Findings showed all 4 therapeutic classes reduce proteinuria, but to varying degrees. Nonimmunosuppressive therapies achieved about a 34% reduction, while corticosteroids and B-cell modulating agents produced 45–50% reductions. Complement inhibitors also showed benefit with about a 35% reduction, though the available data are more limited.4

Kidney function outcomes followed a similar pattern, with data from trials reporting eGFR slope over > 12 months indicating benefits for all drug classes, but with some evidence that effects varied by class. Specifically, nonimmunosuppressive therapies slowed eGFR decline by roughly 28%, corticosteroids by 52%, and B-cell–directed agents by as much as 73%.4

“We have to be a little bit careful about these indirect comparisons across trials because these are very different populations across the studies,” Neuen explained. “What it does suggest, or at least raise the possibility of, is that how we reduce proteinuria is at least as important as to what extent we reduce proteinuria. What this highlights is the really important role of targeting the underlying immunological basis of the disease, where we see that the rates of GFR decline are substantially improved, in particular with the B cell modulating agents.”

Looking ahead, Neuen points to the need for safety data on the B-cell modulating agents, citing a current lack of complete 2-year eGFR slope data and accompanying safety data. From a research perspective, he raises questions about how to best evaluate these therapies in combination and generate evidence supporting the potential role of combination therapy for IgAN.

Editors’ note: Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others.

References

1. Campbell P. Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy. HCPLive. April 3, 2025. Accessed September 22, 2025. https://www.hcplive.com/view/atrasentan-vanrafia-receives-accelerated-approval-in-igan

2. Brooks A. FDA Approves Travere Therapeutics’ Sparsentan to Slow Kidney Function Decline in Adult Primary IgAN. HCPLive. September 5, 2024. Accessed September 22, 2025. https://www.hcplive.com/view/fda-approves-travere-therapuetics-sparsentan-for-proteinuria-reduction-in-adult-primary-igan

3. Campbell C. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. HCPLive. August 8, 2024. Accessed September 22, 2025. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy

4. Kim D, Neuen BL, Perkovic V, Wong MG. Effects of Therapies on Proteinuria and Estimated Glomerular Filtration Rate in IgA Nephropathy: Meta-Analysis of Randomized Trials. Clin J Am Soc Nephrol. doi:10.2215/CJN.0000000839