Shikha Wadhwani, MD, MS

Counting down the biggest news from major medical meetings, it's the HCPLive Five!

HCPLive Five at European Renal Association (ERA) Congress 2025

European Renal Association (ERA) Congress

 is a medical conference bringing together world-renowned experts, researchers, and practitioners in nephrology. 2025’s meeting was hosted in Vienna, Austria, and saw more than 10,000 participants from around the world with a record 2835 abstract submissions from 91 countries. This year’s conference was centered around the theme “Game Changers in Nephrology” with the slogan “Beyond Nephrology,” boasting a comprehensive and innovative program exploring the latest advancements and transformative ideas in nephrology.

As part of HCPLive’s on-site coverage, the editorial team conducted expert interviews and reported on timely topics across therapeutic advances, pipeline updates, new renal clinical trial data, and more. In this edition of the HCPLive Five, the team highlights key conversations on pegcetacoplan in 

 and idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN), a trio of 

 drugs in clinical development, and the potential benefits of simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with 

Pegcetacoplan Sustains Proteinuria Reductions in C3G, IC-MPGN at 52 Weeks

Extended data from the phase 3 VALIANT trial were presented at ERA 2025 and support the sustained efficacy and safety of pegcetacoplan (Empaveli) in patients with C3G or IC-MPGN, including adolescents and adults with native or transplanted kidneys. The 52-week results show continued proteinuria reduction and eGFR stabilization in both treatment-naïve and crossover groups, reinforcing 26-week data presented at the American Society of Nephrology’s 2024 Scientific Sessions.

In this on-site interview at the meeting, Fadi Fakhouri, MD, PhD, co-lead principal investigator for the VALIANT study and a professor of nephrology at CHUV Lausanne, Switzerland, describes pegcetacoplan’s long-term potential in C3G and IC-MPGN and how the data presented at ERA could shift treatment strategies.

Understanding Zigakibart's Potential in IgA Nephropathy, with Jonathan Barratt, MD, PhD

100-week data from the phase 1/2 ADU-CL-19 trial presented at ERA suggest zigakibart, an APRIL inhibitor under development by Novartis, offers durable reductions in proteinuria and maintains a favorable safety profile in patients with IgAN. In the study, patients experienced a mean 60% reduction in proteinuria from baseline, with 55% achieving proteinuria below 500 mg and 31% below 300 mg, as described by Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in this interview. Additionally, serum IgA and pathogenic Gd-IgA1 levels dropped by 74%, building on earlier 52-week data showing reductions in IgA, IgM, and IgG of 67%, 78%, and 35%, respectively.

Kidney Compass: CONFIDENCE Trial at ERA 2025, with Rajiv Agarwal, MD, MS

Simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with CKD and type 2 diabetes was well-tolerated and resulted in significantly greater reductions in urinary albumin-to-creatinine ratio (UACR) than either agent alone, according to results from the CONFIDENCE trial. During ERA, Kidney Compass host Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and the director of the Kidney Trials Unit with Royal North Shore Hospital, held a discussion with trial investigators Rajiv Agarwal, MD, Professor Emeritus at Indiana University School of Medicine, about the study results and what they mean for CKD management landscape in real-world settings.

Phase 3 ORIGIN Sets Stage for Atacicept in IgA Nephropathy, with Richard Lafayette, MD

Just days before the ERA 2025, the nephrology community welcomed and celebrated new positive data for atacicept in IgAN in the form of topline results from the phase 3 ORIGIN trial. Announced by Vera Therapeutics on June 02, 2025, the data indicate the trial met its primary endpoint of reduction in proteinuria at week 36, with the atacicept group achieving a 46% reduction from baseline and a statistically significant 42% reduction compared to placebo at week 36.

’s coverage of ERA, we sat down with Lafayette to discuss how this latest data adds to our understanding of atacicept and its potential role in the management of IgAN if it were to receive FDA approval.

Kidney Compass: Sibeprenlimab and the VISIONARY Trial, with Vlado Perkovic, MBBS, PhD, at ERA 2025

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Vlado Perkovic, MBBS, PhD, dean and scientia professor of Medicine at UNSW Sydney, as he dives into one of the meeting’s most anticipated releases—

. Less than 2 weeks prior to the presentation, Otsuka Pharmaceutical Co. announced the US Food and Drug Administration had granted priority review for their BLA and the application has been given a target action date of November 28, 2025.

These 5 represent only some of the data the 

 team covered at this year's meeting! Check out more KOL insight and our full conference coverage on our 

Videos

From new data for potential IgAN treatments to the use of combination initiation therapy for type 2 diabetes and CKD, here are 5 key updates from the annual meeting.

Welcome to Kidney Compass: Navigating Clinical Trials!

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

, Shikha Wadhwani sits down with Chee Kay Cheung, MBChB, PhD, of the University of Leicester, on the floor at the 

62nd European Renal Association (ERA 2025) Congress

treatment has come—from what used to feel like “tumbleweeds” in nephrology to a pipeline packed with promising therapies.

At the top of the conversation: the rise of B-cell modulating therapies targeting APRIL and BAFF. Cheung highlights the interim results from the global phase 3 VISIONARY trial of sibeprenlimab, an APRIL inhibitor that achieved a 51.2% placebo-adjusted reduction in proteinuria at 9 months—the largest seen in any IgAN phase 3 study to date. Safety data were encouraging, with low discontinuation rates and a favorable overall profile.

Also on the radar: new long-term data from zigakibart, another anti-APRIL antibody, and promising topline results from atacicept, which targets both APRIL and BAFF. While head-to-head comparisons remain elusive, future eGFR outcomes and biomarker studies may help tailor treatment choices to individual patients.

The discussion then shifts to recently approved agents. A post-hoc analysis of the NefIgArd trial found that oral budesonide’s efficacy was consistent across a range of baseline eGFR values. Cheung also spotlights the PROTECT trial’s open-label extension, where patients switching from maximally dosed irbesartan to sparsentan still saw proteinuria reductions of approximately 40%, reinforcing the added value of endothelin receptor antagonism.

During the conversation, Cheung also previews upcoming biopsy-based data from the SPARTAN study, which will explore how sparsentan impacts intrarenal inflammation and fibrosis. With innovation accelerating across drug classes, mechanisms, and biomarker strategies, this year’s ERA meeting evidences that nephrology, but more specifically the IgAN treatment landscape, has moved far beyond tumbleweeds—and into a new era of precision and promise.


 include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Relevant disclosures for 

 include Travere Therapeutics, Alexion, Alpine Immune Sciences, Calliditas Therapeutics, CSL Vifor, Novartis, Otsuka Pharmaceutical, Roche, Vera Therapeutics, and others.

Perkovic V. Sibeprenlimab for Patients With IgA Nephropathy: Results From a Prespecified Interim Analysis of the Phase 3 VISIONARY Study. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

Barratt J, Lee E.Y., Kim S.G., et al. Sustained Long-Term Efficacy and Safety of Zigakibart Over 100 Weeks in Patients with IgA Nephropathy. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

Vera Therapeutics. Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics. Published June 2, 2025. Accessed June 5, 2025. 

https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-atacicept-achieved-46-proteinuria

Barratt J, Lafayette R, Reich HN, et al. Nefecon provides kidney benefit irrespective of baseline eGFR in patients with IgAN: a subanalysis of the NefIgArd study. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

Floege J, Risk DV, Preciado P, et al. Effects of Sparsentan After Maximized Angiotensin Receptor Blocker (ARB) Treatment in Patients With IgA Nephropathy (IgAN) in the PROTECT Trial. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

Podcasts

A deep dive into several noteworthy IgAN studies presented during the ERA 2025 Congress. 

, hosts are joined by Vlado Perkovic, MBBS, PhD, dean and scientia professor of Medicine at UNSW Sydney, at the 

. During the episode, Perkovic takes hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, on a deep dive into 1 of the meeting’s most anticipated releases—

. Billed as the largest phase 3 trial ever conducted in IgA nephropathy (IgAN), the global study spanned 31 countries and randomized 510 participants in a 1:1 ratio to sibeprenlimab or placebo therapy.

Less than 2 weeks prior to the presentation, Otsuka Pharmaceutical Co. announced the US Food and Drug Administration had granted priority review for their BLA and the application has been given a target action date of November 28, 2025. Perkovic, who also serves as a professorial fellow at The George Institute and a staff specialist in Nephrology at the Royal North Shore Hospital in Sydney, shares how sibeprenlimab—a targeted APRIL inhibitor—achieved a significant 50.2% reduction in geometric mean 24-hour urine protein-to-creatinine ratio (uPCR) from baseline after 9 months of treatment while the placebo group saw a slight increase of 2.1%, yielding a between-group difference of 51.2% (96.5% CI, 42.9% to 58.2%; 

According to Perkovic, what makes this data even more compelling is the context: 98% of participants were on renin-angiotensin system inhibitors and 39% were also taking SGLT2 inhibitors at baseline, suggesting that sibeprenlimab delivered a significant additional benefit beyond optimized standard of care.

Throughout the conversation, Perkovic offers key insights into the rationale for targeting APRIL in IgAN, the design considerations behind the VISIONARY trial, and what this could mean for the future of therapy. He emphasizes the importance of proteinuria as a prognostic marker and discusses how a reduction of this magnitude could correlate with longer-term eGFR stabilization—data expected in a future analysis.

Tune in to hear Perkovic’s expert take on how VISIONARY is not only changing the narrative around IgAN treatment, but also setting a new bar for targeted, precision-driven kidney care.

 include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for 

 include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Relevant disclosures for 

 include Boehringer Ingelheim,AbbVie, Inc., Bristol-Myers Squibb, servier, Astellas Pharma US, Merck, Janssen Pharmaceuticals, GSK, and others.

Otsuka Pharmaceutical Co. Otsuka Announces Positive Interim Results from the Phase 3 Trial of Sibeprenlimab for the Treatment of Immunoglobulin A Nephropathy in Adults｜News Releases | Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Published October 22, 2024. Accessed June 6, 2025. 

https://www.otsuka.co.jp/en/company/newsreleases/2024/20241022_1.html

Discover groundbreaking insights on the VISIONARY trial, IgA nephropathy treatment, and the future of kidney care with expert Vlado Perkovic, MBBS, PhD.

Kidney Compass: Applying Hierarchical Composite Endpoints in Kidney Disease Trials

In the final installment of our 4-part episode of 

, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, are joined by special guests Dustin Little, MD, and Niels Jongs, PhD, as they discuss the application of hierarchical composite endpoints (HCEs) in specific kidney disease subpopulations and rare disease trials.

Wadhwani highlights the need to tailor HCEs to disease-specific priorities, such as relapse reduction and immunosuppression minimization in lupus nephritis. The discussion then shifts to subgroup analyses in trials using HCEs. While traditional trials are powered for the overall population, subgroup analyses often lack statistical power. Jongs explains that increasing the efficiency of HCE-powered trials may allow for better-powered subgroup analyses, but achieving statistical certainty in smaller populations remains challenging.

The panel explores a real-world example of focal segmental glomerulosclerosis (FSGS) within the DAPA-CKD trial, where traditional analyses showed numerical benefits of dapagliflozin but lacked statistical significance due to wide confidence intervals. Jongs and Little discuss how applying HCEs and win odds in these cases could refine statistical assessments and potentially strengthen findings, offering greater confidence in treatment effects.

The episode concludes with reflections on the future of HCEs in nephrology research, emphasizing their potential to optimize trial efficiency, improve data interpretation, and advance therapies for rare and complex kidney diseases.

For ease of viewing, we've divided this episode into 4 sections and highlighted them below.

Kidney Compass: Hierarchical Composite Endpoints in Nephrology

Part 1: Introductions, HCEs in Nephrology

Part 2: HCEs in Nephrology Clinical Trials

Part 3: Addressing HCE Skepticism, Potential Limitations

Part 4: Applying HCEs in Kidney Disease Trials

 include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for 

 include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for 

In the final segments of this 4-part episode, the discussion focuses on the use of HCEs in different kidney disease trials.

Shikha Wadhwani, MD, MS

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