IgA Nephropathy in 2025: Year in Review

In 2025, therapeutic modalities for IgA nephropathy (IgAN) underwent rapid and consequential changes, signaling newfound opportunity and choice for clinicians in the once-limited treatment landscape.

These developments were marked by multiple US Food and Drug Administration (FDA) approvals, pivotal phase 3 readouts, and an updated 2025 Kidney Disease: Improving Global Outcomes (KDIGO) IgAN guideline. The FDA granted accelerated approval to sibeprenlimab (Voyxact) based on proteinuria reduction in the phase 3 VISIONARY trial, approved atrasentan (Vanrafia) as the first selective endothelin A receptor antagonist for IgAN, and updated the Risk Evaluation and Mitigation Strategy (REMS) requirements for sparsentan (Filspari), reducing liver monitoring frequency and removing embryo-fetal toxicity monitoring.

At the same time, late-stage clinical trials, including APPLAUSE-IgAN evaluating iptacopan (Fabhalta), phase 3 studies of telitacicept, and emerging data for povetacicept and mezagitamab, provided growing evidence of targeted complement inhibition and B-cell modulation slowing disease progression and reducing proteinuria.

These developments, alongside the release of the international clinical guidance, collectively signal a shift toward earlier, mechanism-driven intervention.

FDA News

FDA Approves REMS Label Update for Sparsentan (Filspari) in IgA Nephropathy

On August 27, 2025, Travere Therapeutics announced FDA approval of an updated REMS labeling for sparsentan (Filspari) in IgAN. The update reduces liver function monitoring from monthly to every 3 months and removes embryo-fetal toxicity monitoring, based on safety data from post-marketing surveillance and the phase 3 PROTECT, phase 3 DUPLEX, and phase 2 DUET trials. Less intensive monitoring may improve patient adherence and broaden the practical use of sparsentan in IgAN management.

FDA Awards Accelerated Approval to Sibeprenlimab in IgA Nephropathy

On November 25, 2025, the FDA approved sibeprenlimab (Voyxact), a targeted APRIL inhibitor from Otsuka Pharmaceutical, for reducing proteinuria in adults with primary IgAN at risk for disease progression. Approval was based on results from the VISIONARY trial, the largest phase 3 IgAN study to date, which demonstrated a 54.3% placebo-adjusted reduction in 24-hour urine protein-to-creatinine ratio (UPCR) after 12 months. Sibeprenlimab provides a first-in-class option targeting APRIL, signaling the emergence of mechanism-based therapies beyond conventional supportive care.

Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy

On April 2, 2025, the FDA approved atrasentan, a once-daily, non-steroidal oral endothelin A receptor antagonist, for reducing proteinuria in adults at risk of rapid progression. The approval confirms proteinuria as a regulatory-accepted surrogate endpoint and expands nephrology’s antiproteinuric toolkit.

Related: Progress in IgAN and Future Innovations in Nephrology, with Richard Lafayette, MD

Trial Updates and New Guidelines

Finerenone Shows Promise in IgAN: Reduced Proteinuria, Stable Kidney Function

Finerenone treatment in patients with IgAN on standard supportive care reduced protein-to-creatinine ratio and maintained stable estimated glomerular filtration rate (eGFR) over 6 months, with a 25% relative reduction in urine albumin-to-creatinine ratio (UACR) versus placebo.

These results suggest finerenone may provide kidney protection and reduce cardiovascular risk, expanding its potential role in managing patients with proteinuric kidney disease.

Povetacicept Data Validate APRIL/BAFF Inhibition in IgAN and pMN, With James Tumlin, MD

In the phase 1/2 RUBY-3 trial, povetacicept led to sustained reductions in UPCR, galactose-deficient IgA1 (Gd-IgA1), and hematuria, while maintaining stable eGFR in patients with IgAN and primary membranous nephropathy (pMN). James Tumlin, MD, highlighted that these upstream immunologic effects translate into meaningful proteinuria reductions. Povetacicept reinforces the potential of B-cell–modulating therapies to achieve disease-modifying outcomes in IgAN.

APPLAUSE-IgAN: Iptacopan (Fabhalta) Meets eGFR Decline Primary Endpoint

The phase 3 APPLAUSE-IgAN trial demonstrated that iptacopan, an oral alternative complement pathway inhibitor, significantly slowed IgAN progression, measured by the annualized total slope of eGFR decline over 2 years. Novartis plans to use these data for regulatory submissions in 2026. Iptacopan offers a potential oral complement-targeted therapy that could reduce the burden of progressive kidney loss in IgAN.

Mezagitamab Shows Promise for IgA Nephropathy in Phase 1b Trial, with Jonathan Barratt, MD, PhD

Interim data from a phase 1b trial led by Jonathan Barratt, MD, PhD, suggest mezagitamab, a CD38-targeting monoclonal antibody, achieved meaningful biological and clinical responses with no Grade 3 or higher infections when added to standard care. Early results indicate CD38-targeted therapy may provide a novel immunomodulatory approach for IgAN management.

Telitacicept Achieves Primary Endpoint in IgA Nephropathy Phase 3 Study

RemeGen’s telitacicept, a fusion protein targeting B-lymphocyte stimulator (BLyS) and APRIL, demonstrated efficacy and a favorable safety profile over 39 weeks, reducing UPCR and affecting immunoglobulin levels in high-risk IgAN patients. Telitacicept strengthens the pipeline of B-cell–modulating therapies with the potential to alter disease course in IgAN.

KDIGO Releases Updated IgA Nephropathy, IgA Vasculitis Clinical Practice Guideline

The 2025 KDIGO Clinical Practice Guideline, co-chaired by Jürgen Floege, MD, and Brad Rovin, MD, emphasizes early initiation of therapies targeting both IgA-containing immune complex formation and downstream nephron injury. Guidelines reinforce a precision-based approach, encouraging use of targeted therapies in early disease to prevent irreversible kidney damage.

Feature Content/Podcasts

Kidney Compass: Key Updates in IgA Nephropathy at ERA 2025, with Chee Kay Cheung, MBChB, PhD

Kidney Compass, HCPLive’s nephrology podcast hosted by Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, covered pivotal advances in kidney care throughout 2025.

In this special edition of Kidney Compass, Wadhwani, MD, sits down with Chee Kay Cheung, MBChB, PhD, of the University of Leicester, at the 62nd European Renal Association (ERA 2025) Congress to discuss the evolving treatment landscape of IgAN, including the rise of B-cell modulating therapies targeting APRIL and BAFF.

Kidney Compass: Atacicept and ORIGIN 3 at Kidney Week 2025, with Richard Lafayette, MD

In this featured episode of Kidney Compass at the American Society of Nephrology (ASN) Kidney Week 2025, our hosts sat down with Richard Lafayette, MD, a rheumatologist at Stanford Health Care. They reviewed ORIGIN-3 trial results evaluating atacicept, a dual BAFF/APRIL inhibitor, highlighting its potential to reduce pathogenic IgA1 production and proteinuria in IgAN. Atacicept reinforces the mechanistic approach to IgAN, supporting its integration into precision therapy strategies.

PREVAIL: Felzartamab’s Sustained Clinical Outcomes In IgAN, With Jurgen Floege, MD

In this featured interview from ASN 2025, Jürgen Floege, MD, discussed data from the IGNAZ phase 2 and ongoing PREVAIL phase 3 trials investigating felzartamab, an anti-CD38 agent, which showed durable plasma cell depletion, sustained suppression of IgA, and reduced proteinuria. Felzartamab demonstrates the long-term potential of CD38-targeted therapy to modify the disease course in IgAN.

Shaping the Next Era of IgA Nephropathy Treatment, With Brendon Neuen, MBBS, PhD

Brendon Neuen and a team of investigators evaluated multiple new therapies, iptacopan (Fabhalta), sparsentan (Filspari), atrasentan (Vanrafia), and budesonide (Tarpeyo), considering critical questions about how to best use these treatments in practice.

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 were examined. They found that all 4 therapeutic classes reduce proteinuria, but to varying degrees. Comparative insights help guide the selection of personalized therapy based on mechanism, efficacy, and patient-specific factors.

Factor D Inhibition Lacks Efficacy For IgAN in Phase 2 ALXN2050 Trial, With Sayna Norouzi, MD

Sayna Norouzi, MD, reported that ALXN2050 (vemircopan) did not significantly reduce UPCR versus placebo, underscoring safety concerns and lack of efficacy in IgAN.Even though these results are negative, they may inform the prioritization of alternative therapeutic pathways, refining future drug development strategies in IgAN.