Shikha Wadhwani, MD, MS

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

New phase 3 data released by Vor Bio underscore the potential of telitacicept, a dual BLyS/APRIL inhibitor, as a disease-modifying therapy for 

, particularly for patients at high risk of progression.

Kidney Compass: Navigating Clinical Trials

, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS sit down with study investigators Jicheng Lv, MD, PhD, and Hong Zhang, MD, PhD, professors of internal medicine at Peking University First Hospital, following their presentation at the 

American Society of Nephrology (ASN) Kidney Week 2025

Telitacicept is a recombinant fusion protein designed to neutralize BLyS and APRIL, upstream drivers of B-cell survival and immunoglobulin class switching, including production of galactose-deficient IgA1, the pathogenic hallmark of IgAN. The 39-week multicenter, randomized, double-blind trial evaluated the agent’s impact on proteinuria, B-cell activity, immunoglobulin levels, and kidney function.

In stage A, adults were randomly assigned 1:1 to telitacicept 240 mg subcutaneous weekly or placebo, in addition to background supportive care. The primary endpoint, which was defined as change in 24-hour urine protein-to-creatinine ratio (UPCR), was met with a −58.9% reduction in the telitacicept arm compared with −8.8% with placebo (

 < .0001). Week-39 data were consistent, with the treatment group showing a 55% 24-hour UPCR reduction.

Clinically meaningful thresholds associated with improved long-term renal outcomes were achieved at substantially higher rates with telitacicept:

24h-UPCR <0.8 g/g: 61% vs 19.5% (placebo)

Investigators highlighted kidney function remained stable across secondary endpoints. Mean eGFR change at week 39 was essentially unchanged with telitacicept (−0.010 mL/min/1.73 m²) compared with a modest decline in the placebo group (−0.77 mL/min/1.73 m²). Investigators also observed a lower risk of ≥30% eGFR decline (27%) with telitacicept versus placebo.

Editor's Note: LV reports relevant disclosures with Chinook Therapeutics, KBP Bioscience, and others. Zhang reports no relevant disclosures

Lv, J, Liu LJ, Wang W, et al. Efficacy and Safety of Telitacicept in Patients with IgAN: Results from Stage A of a Phase 3 Clinical Study. 

Journal of the American Society of Nephrology

Telitacicept Achieved Primary Endpoint in Phase 3 Clinical Study for IgA Nephropathy | Vor Bio. Vor Bio. Published 2025. https://ir.vorbio.com/news-releases/news-release-details/telitacicept-achieved-primary-endpoint-phase-3-clinical-study-0

Podcasts

Dual BLyS/APRIL inhibition with telitacicept cut proteinuria and maintained kidney function in adults with IgA nephropathy.

Welcome to Kidney Compass: Navigating Clinical Trials!

Kidney Compass: SMART-C at ASN Kidney Week 2025

, Brendon Neuen, MBBS, PhD, doubles as a host and special guest as he offers host Shikha Wadhwani, MD, MS, a deep dive into the latest data from the the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C) at the 

the large-scale meta-analyses provide comprehensive evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce the risk of 

 progression, kidney failure, and related adverse outcomes across all levels of kidney function and albuminuria, regardless of diabetes status.

In the first analysis, the SMART-C team evaluated 70,361 participants from 10 randomized, placebo-controlled trials of SGLT2 inhibitors. Participants had a mean (SD) age of 64.8 (SD, 8.7) years, and 35.0% were female. During a median follow-up of 3 years, 2314 participants (3.3%) experienced CKD progression and 988 (1.4%) reached kidney failure.

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% 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)

<30 mL/min/1.73 m²: HR, 0.71 (95% CI, 0.60–0.83); 

Similar protection was observed across urinary albumin-to-creatinine ratio (UACR) levels, with HRs of 0.58 (95% CI, 0.44–0.76) for ≤30 mg/g, 0.74 (95% CI, 0.57–0.96) for 30–300 mg/g, and 0.57 (95% CI, 0.52–0.64) for >300 mg/g (

 for trend = .49). SGLT2 inhibitors also attenuated annual eGFR decline across all subgroups, including those without diabetes.

A complementary meta-analysis of 58,816 participants, including 48,946 with diabetes and 9870 without diabetes, across 8 clinical trials confirmed the broad efficacy and safety of SGLT2 inhibitors. Treatment significantly reduced kidney disease progression (HR, 0.65 [95% CI, 0.60–0.70] in diabetes; HR, 0.74 [95% CI, 0.63–0.85] without diabetes), acute kidney injury (HR, 0.77 [95% CI, 0.69–0.87] and HR, 0.72 [95% CI, 0.56–0.92]), all-cause hospitalization (HR, 0.90 [95% CI, 0.87–0.92] and HR, 0.89 [95% CI, 0.83–0.95]), and all-cause death (HR, 0.86 [95% CI, 0.80–0.91] and HR, 0.91 [95% CI, 0.78–1.05]).

Check out this interview with presenting investigator Natalie Staplin, PhD, for more on the 8-trial meta-analysis!

The magnitude of benefit was consistent across albuminuria strata (UACR ≥ 200 mg/g vs <200 mg/g), although absolute risk reductions were greater in those with higher baseline albuminuria.

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

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

Neuen BL, Fletcher RA, Anker SD, et al. SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria: A Meta-Analysis. 

 Published online November 07, 2025. doi:

Staplin N, Roddick AJ, Neuen BL, et al. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. 

Discover groundbreaking insights on SGLT2 inhibitors and their impact on kidney health, cardiovascular outcomes, and patient care at ASN Kidney Week.

Kidney Compass: Lafayette and ORIGIN 3 at Kidney Week 2025

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Ricahrd Lafayette, MD, from the floor at the 

 evaluating atacicept and how it adds to the totality of evidence supporting the use of the dual BAFF/APRIL inhibitor in IgA nephropathy (IgAN). 

Lafayette describes the moment as “predictably exciting,” noting that the phase 3 findings strongly mirror the promising signals seen previously in the ORIGIN phase 2 program.

The phase 2 trial, which evaluated weekly atacicept dosing, demonstrated a robust biologic impact with approximate reductions of 75% in galactose-deficient IgA1 and 50% in proteinuria at 96 weeks, hematuria resolution in most affected patients, and an annual eGFR decline of only ~0.6 mL/min/1.73 m², which Lafayette noted was far below the expected trajectory in this population. These data guided the design of ORIGIN 3, which enrolled biopsy-proven IgA nephropathy with >1 g/day of proteinuria, eGFR >30 mL/min/1.73 m², and maximally tolerated background therapy. More than half of the participants were also taking an SGLT2 inhibitor. 

Lafayette reports the 9-month primary outcome results aligned closely with phase 2. 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. Lafayette highlighted these effects were consistent across prespecified subgroups, including those on SGLT2 inhibitors.

Safety findings demonstrated there was no increase in infections or serious adverse events relative to placebo, aside from mild injection-site reactions. Lafayette pointed out, numerically, severe adverse events occurred more often in the placebo arm.

While regulatory restrictions prevent release of 9-month eGFR data, Lafayette notes the close resemblance to the phase 2 trajectory supports optimism for the upcoming 2-year readout. However, he emphasizes that atacicept-related biomarker improvements reverse when treatment stops, indicating that ongoing therapy may be necessary for sustained benefit.

The discussion concludes by situating atacicept within a rapidly expanding therapeutic landscape, including other B-cell–directed agents targeting APRIL alone. Head-to-head differences remain unknown, but atacicept’s dual BAFF/APRIL inhibition and consistent efficacy across optimized background therapy make it a compelling potential addition.

 include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others. Relevant disclosures for 

Lafayette R, Barbour SJ, Brenner RM, et al. 

ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN

. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

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

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

Discover groundbreaking insights from the ORIGIN 3 study on IgA nephropathy, showcasing promising results and future treatment possibilities.

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

Unmet Needs and Unanswered Question in C3G

, Shikha Wadhwani, MD, MS, Anuja Java, MD, and Corey Cavanaugh, DO, reflect on the promise and challenges of integrating FDA-approved therapies like pegcetacoplan and iptacopan into clinical practice for patients with 

C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN)

A New Era for C3G Treatment with Pegcetacoplan

Navigating Targeted Therapies for C3 Glomerulopathy

Understanding Pegcetacoplan in C3G with VALIANT Data

Approaching Incident C3G in an Era of Targeted Therapies

Unmet Needs and Unanswered Questions in C3G

While both approvals mark a major step forward, the panel is candid about the real-world barriers that still stand in the way, with access to therapy chief among them. Cavanaugh emphasizes the logistical and financial hurdles in securing these high-cost drugs, even for young patients who may urgently need them. He anticipates that larger academic centers and designated centers of excellence will play a crucial role in helping regional providers navigate these complexities and secure timely treatment.

Java shares the same enthusiasm about having disease-targeted options but flags the persistent frustrations of insurance denials, even for long-established complement inhibitors. Both she and Cavanaugh express ongoing uncertainty about how to apply trial findings to the diverse patient populations seen in practice, especially those with atypical presentations or no clear genetic or functional complement driver. They also grapple with how best to manage transplant patients, many of whom may be on anti-C5 therapy already and raise questions about whether upstream inhibition might offer better long-term outcomes.

The discussion also touches on the lack of predictive tools to determine who will respond to therapy, who will progress, and when and how often repeat biopsies should be performed in seemingly stable patients.

As Wadhwani notes in closing, nephrologists are entering a new era in C3G marked by momentum, collaboration, and the opportunity to finally align pathophysiology with treatment. The panel agrees the key now is to ensure that the promise of clinical trial data translates into equitable, durable outcomes for patients across practice settings.

 is an associate professor of Medicine and the vice chair of Clinical Research at the University of Texas Medical Branch. Wadhwani, who is the co-host of HCPLive’s 

 and member of our advisory board, serves as the moderator for this conversation.

 is an associate professor and transplant nephrologist at Washington University School of Medicine in St. Louis and director of Kidney Transplantation at John Cochran VA Medical Center in St. Louis.

 is a staff nephrologist at the Cleveland Clinic.

 include Otsuka Pharmaceuticals, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for 

 include Alexion, AstraZeneca, Novartis, Dianthus Therapeutics, Aurinia Pharmaceuticals Inc., Apellis and UptoDate.

 include Vera Therapeutics and Travere Therapeutics.

Apellis Pharmaceuticals. FDA Approves Apellis’ EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older | Apellis Pharmaceuticals, Inc. Apellis Pharmaceuticals, Inc. Published July 28, 2025. Accessed August 4, 2025. 

https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and

Nester CM, Bomback AS, Ariceta G, et al. VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). 

US Food and Drug Administration. Fabhalta approved for complement 3 glomerulopathy. U.S. Food and Drug Administration. Published March 20, 2025. Accessed August 4, 2025. 

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce

Videos

In the final segment of this 5-part HCPLive RX Review, experts discuss real-world barriers to implementing new C3G therapies and lingering unmet needs.

Shikha Wadhwani, MD, MS

Articles