Shaping the Next Era of IgA Nephropathy Treatment, 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

In a recent systematic review and meta-analysis of pooled phase 2 and phase 3 trial data for nonimmunosuppressive antiproteinuric therapies, corticosteroids, B-cell modulating agents, and complement inhibitors, 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, and a team of investigators found all 4 therapeutic classes reduce proteinuria, but to varying degrees.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.4

“What I'm really looking forward to seeing, and I think many others are looking forward to as well, is the safety data from ongoing phase 3 trials of the immunological therapies, particularly the B cell related therapies, APRIL and BAFF inhibitors, because of the tremendous potential that these agents have in preventing kidney function decline,” Neuen told HCPLive. “If the safety data is as good as what is suggested in earlier phase studies, I think that will really help guide treatment selection in IgA nephropathy.”

However, in the absence of head-to-head data, the practical question of sequencing therapies remains unsettled, with Neuen referencing a recent episode of Kidney Compass on the VISIONARY trial with guest Vlado Perkovic, MBBS, PhD, dean and scientia professor of Medicine at UNSW Sydney.

“I think this is where cost, availability, and other practicalities are going to come into play,” Neuen said. “Of course, it's always going to be preferable to target the immunological basis of the disease. But in many health care settings around the world, these agents may not be available, or if they are, they may be available at considerable costs.”

From a practical perspective, he says clinicians will be accessing therapies readily available to them, likely meaning nonimmunological antiproteinuric therapies will be used first and additional therapies will be added later.

Looking ahead, Neuen says he sees a “great opportunity” to explore a more personalized approach to IgAN therapeutics, but notes there are challenges in doing so with so many therapies available and limited ability to determine which patients will respond to which treatment.

“We're obviously not there yet, but I think that's the great opportunity and a real call to arms in terms of mechanistic research to identify biomarkers so that we can sequence these therapies and prioritize individuals for whom these drugs may work better,” Neuen said.

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 24, 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 24, 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 24, 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