Generative year-long progress in nephrology enabled an abundant final quarter of 2025, immersed in US Food and Drug Aministration (FDA) news, clinical trial updates, and breakthroughs, as well as bustling content from HCPLive’s nephrology podcast, Kidney Compass: Navigating Clinical Trials, and ground floor coverage from the American Society of Nephrology (ASN) Kidney Week 2025.

FDA updates included Orphan Drug Designation to ABBV-CLS-628 for the treatment of autosomal dominant polycystic kidney disease (ADPKD), accelerated approval for sibeprenlimab (Voyxact) for reducing proteinuria in primary IgA nephropathy (IgAN), Breakthrough Device Designation for Holly™ implantable, continuous dialysis system, and a supplemental New Drug Application (sNDA) for the furosemide On-body Infusor (FUROSCIX) to treat edema associated with chronic heart failure (HF) and chronic kidney disease (CKD), as well as for FUROSCIX ReadyFlow Autoinjector.

In the IgAN landscape specifically, there are > 5 drugs in late-phase clinical development showing similar proteinuria reductions, and > 20 clinical trials underway, offering an emerging opportunity for patients and clinicians’ treatment choice. Further investigation into the long-lasting safety and efficacy of therapeutics, such as finerenone, felzartamab, telicacicept, povetacicept, atacicept, and others, will continue as 2026 unfolds and quarter 1 begins.

To read the highlights from quarter 4 of 2025, check out HCPLive’s editorial coverage below:

FDA News

FDA Grants Orphan Drug Designation to ABBV-CLS-628 for ADPKD

On November 5, 2025, the FDA granted Orphan Drug Designation to ABBV-CLS-628, an investigational therapy for the treatment of ADPKD.

The designation stemmed from the ongoing phase 2, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of intravenous ABBV-CLS-628 in adults with ADPKD, measuring changes in total kidney volume, estimated glomerular filtration rate (eGFR) decline, and secondary measures of patient quality of life, biomarker responses, and treatment tolerability.

The study duration is 92 weeks, with a 15-week safety follow-up period.

FDA Awards Accelerated Approval to Sibeprenlimab in IgA Nephropathy

Accelerated approval was given to sibeprenlimab (Voyxact) for reducing proteinuria in primary IgAN in adults at risk for disease progression, on November 25, 2025. The targeted APRIL inhibitor was examined in the VISIONARY trial, billed by Otsuka Pharmaceutical Co. as the largest phase 3 trial ever conducted in IgAN.

The therapy was associated with a 54.3% placebo-adjusted reduction in geometric mean 24-hour urine protein-to-creatinine ratio (UPCR) from baseline after 12 months of treatment. The full 2-year results, which will include eGFR, are expected to be released in 2026.

FDA Grants Breakthrough Device Designation to Holly Implantable Dialysis System

Nephrodite’s Holly™ implantable, continuous dialysis system was granted Breakthrough Device Designation by the agency on December 15, 2025, which recognized it as a novel, transformative therapy addressing end-stage kidney disease (ESKD).

The company announced successful results from a 72-hour preclinical animal trial study, including the first considered demonstration of sustained, continuous kidney function replacement by a fully mechanical implantable device in a living sheep, without the complications typically associated with current dialysis technologies.​​

Nephrodite is preparing for Good Laboratory Practice studies and subsequent regulatory submissions to enable first-in-human clinical trials.

FDA Approves FUROSCIX On-Body Injector for Pediatric Patients, Accepts sNDA for ReadyFlow Autoinjector

On December 23, 2025, MannKind announced the FDA had approved a sNDA for the furosemide On-body Infusor (FUROSCIX) to treat edema associated with chronic HF and CKD in pediatric patients weighing ≥43 kg.

In the same release, the company announced the acceptance of a sNDA for the FUROSCIX ReadyFlow Autoinjector for adult patients with chronic HF or CKD, which is designed to deliver a subcutaneous furosemide injection in < 10 seconds. The implications of an approval could mean a method for patients to manage fluid buildup from home, thereby eliminating the need for hospital admission.

Trial Updates

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

Jürgen Floege, MD, principal investigator of the STOP-IgAN trial and senior professor at RWTH Aachen University’s Medical School, sat down with HCPLive after presenting new findings on felzartamab from the PREVAIL trial at ASN Kidney Week 2025.

Felzartamab, a CD38-targeted therapy, demonstrated successful depletion of plasma cells, while immunoglobulins recovered; however, IgA remained suppressed, proteinuria remained reduced, and galactose-deficient IgA (GDiGA) rebounded in the IGNAZ phase 2.

PREVAIL, the ongoing 104-week phase 3 multicenter, randomized, double-blind, placebo-controlled trial, aims to evaluate further the efficacy and safety of felzartamab in adults with IgAN and consists of a 24-week treatment period where patients are randomly assigned to receive felzartamab or placebo, followed by an 80-week off-medication study.

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

In the FINE-ONE trial, finerenone showed a significant reduction in the protein-to-creatinine ratio and stable estimated glomerular filtration rate (eGFR) during follow-up when treating patients with IgAN receiving full supportive care.

The data suggest a protective effect of finerenone on renal function, reduced risk of cardiovascular events, and a statistically significant 25% relative reduction in the urine albumin-to-creatinine ratio compared with the placebo in 6 months.

Telitacicept Achieves Primary Endpoint in IgA Nephropathy Phase 3 Study

RemeGen’s telitacicept, a novel fusion protein and B-cell modulating biologic, exhibited efficacy and a favorable safety profile in adults with IgAN at a high risk of disease progression.

In the phase 3 study, telitacicept achieved its primary endpoint of reducing proteinuria, with a -58.9% change in 24-hour urine protein-to-creatinine ratio (24h-UPCR) compared with -8.8% for placebo (P <.0001). At week 39, the treatment group showed a 55% reduction in 24h-UPCR. A greater proportion of patients receiving telitacicept achieved thresholds associated with lower progression risk: 61% vs 19.5% achieved 24h-UPCR <0.8 g/g, 42.1% vs 7.5% achieved <0.5 g/g, and 24.5% vs 0.6% achieved <0.3 g/g.

Related: Kidney Compass: Phase 3 Data on Telitacicept in IgA Nephropathy at ASN Kidney Week 2025.

VALIANT: Pegcetacoplan Shows Sustained Efficacy in C3G and IC-MPGN, With Carla Nester, MD

Pegcetacoplan, the first FDA-approved therapy for C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), showed sustained proteinuria reductions and stable estimated eGFR in a 26-week open-label extension of the phase 3 VALIANT trial.

HCPLive spoke with study investigator Carla Nester, MD, a professor of pediatrics-nephrology at the University of Iowa, about the implications of the results.

Investigators reported patients maintained a 70% reduction in proteinuria over 52 weeks in adolescents, with many patients achieving remission (≤0.5 g/g) or normalization (≤0.2 g/g). At 52 weeks, pegcetacoplan-treated patients saw stabilized eGFR in both adolescents and adults, signaling the therapy may have the potential to change disease trajectory.

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

HCPLive spoke with James Tumlin, MD, an adjunct professor from the department of medicine at Emory University School of Medicine, about the data he presented at Kidney Week 2025 on povatecicept, a BAFF and APRIL inhibitor.

In findings from the phase 1/2 RUBY-3 trial, povatacicept led to substantial, sustained 64% mean reduction in 24-hour UPCR with stable eGFR, significant Gd-IgA1 reductions, hematuria resolution, clinical remission, with favorable safety in IgAN and primary membranous nephropathy (pMN).

The therapy was generally well-tolerated across both diseases, with Tumlim expressing the possibility of povetacicept as a disease-modifying therapy, distinct from hemodynamic or anti-proteinuric approaches.

Feature Content/Podcasts

In the last quarter of 2025, Kidney Compass: Navigating Clinical Trials, podcast hosts Shikha Wadhwani, MD, MS, and Brendon Neuen, MBBS, PhD, sat down with nephrology clinical trial investigators and experts to break down their findings for HCPLive’s audience.

Kidney Compass: Understanding Renal Outcomes in SURPASS-CVOT

In this podcast episode, Neuen sat down with Sophia Zoungas, MBBS, PhD, an endocrinologist and head of the School of Public Health and Preventive Medicine at Monash University, to discuss a post hoc analysis of the phase 3 SURPASS-CVOT trial.

The findings showed tirzepatide (Mounjaro) significantly slowed kidney function decline and reduced albuminuria progression compared with dulaglutide (Trulicity) in patients with type 2 diabetes, atherosclerotic cardiovascular disease (ASCVD), and very high-risk CKD.

At 36 months, tirzepatide was associated with a significantly smaller decline in eGFR compared to dulaglutide: −3.0 (±0.5) mL/min/1.73 m² with tirzepatide vs −7.2 (±0.4) with dulaglutide (between-group difference: +4.1 mL/min/1.73 m²; P <.001), as well as reductions in urinary albumin-to-creatinine ratio (UACR) −45.6% with tirzepatide vs −28.0% with dulaglutide (between-group difference: −24.6%; P <.001).

No new safety concerns were identified, and benefits were consistent regardless of baseline SGLT2 inhibitor use.

Kidney Compass: Obinutuzumab, REGENCY, & Updates in Lupus Nephritis, With Brad Rovin, MD

At ASN Kidney Week 2025, Wadwhani sat down with Brad Rovin, MD, Lee A. Hebert Distinguished Professor of Nephrology at The Ohio State University Wexner Medical Center, to discuss a late-breaking analysis of the phase 3 REGENCY trial in obinutuzumab in patients with lupus nephritis.

REGENCY is the first successful phase 3 anti-CD20 trial in lupus nephritis, showing a higher complete renal response with obinutuzumab. Tissue-level biomarker data confirmed near-complete renal B-cell depletion with obinutuzumab, citing a median change of –98.3% from baseline, compared to a +29.8% increase with placebo. Plasma cell counts declined by 57.1% with obinutuzumab versus +2.7% in the placebo arm, confirming deep immunologic inactivation within the kidney.

Kidney Compass: Setanaxib, Alport Syndrome, and RaDaR Updates at Kidney Week 2025

Neuen sat down with Daniel Gale, PhD, MB BChir, who is the director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, to discuss a phase 2 trial of setanaxib in Alport syndrome for patients at risk for disease progression despite optimized background therapy.

The findings from the phase 2a clinical trial suggest setanaxib, a novel enzyme-driven hydrogen peroxide depleting agent with antifibrotic properties, was associated with a 15% mean reduction in UPCR at week 24 versus placebo. Of note, a 27% mean UPCR reduction was observed 4 weeks after treatment discontinuation, suggesting a sustained pharmacodynamic effect.

Kidney Compass: SMART-C at ASN Kidney Week 2025

In this special edition episode, Wadwhani interviews resident host, Neuen, as a special guest to discuss the latest data from the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C) during ASN’s Kidney Week.

SGLT2 inhibitors reduced the risk of CKD progression by 38% (25.4 vs 40.3 events per 1000 patient-years; hazard ratio [HR], 0.62 [95% Confidence Interval [CI], 0.57-0.68]), with consistent efficacy across eGFR categories: ≥60 mL/min/1.73 m²: HR, 0.61 (95% CI, 0.52–0.71); 45 to <60 mL/min/1.73 m²: HR, 0.57 (95% CI, 0.47–0.70); 30 to <45 mL/min/1.73 m²: HR, 0.64 (95% CI, 0.54–0.75); and <30 mL/min/1.73 m²: HR, 0.71 (95% CI, 0.60–0.83); P for trend = .16.

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

In another episode filmed during ASN Kidney Week 2025, Neuen and Wadhwani are joined by Richard Lafayette, MD, to discuss the late-breaking ORIGIN 3 results evaluating atacicept and its supportive evidence for the use of the dual BAFF/APRIL inhibitor in IgAN.

The phase 3 findings showed atacicept achieved >45% reductions in proteinuria, compared with approximately 7% in the placebo group. Gd-IgA1 fell by approximately 75–80%, and hematuria resolved in most atacicept-treated patients with minimal change on placebo.