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

, host Shikha Wadhwani, MD, MS, sits down with Brad Rovin, MD, Lee A. Hebert Distinguished Professor of Nephrology at The Ohio State University Wexner Medical Center, to discuss updates in lupus nephritis at the 

, including a late-breaking analysis of the phase 3 REGENCY trial.

Building on the phase 2 NOBILITY signal and addressing lessons from the negative LUNAR rituximab study, where depth of B-cell depletion predicted response, REGENCY is the first successful phase 3 anti-CD20 trial in LN, showing a higher complete renal response (CRR) with obinutuzumab. The phase 3 trial randomized adults with active LN to obinutuzumab (Gazyva) plus standard therapy, which was defined as mycophenolate mofetil (MMF) and glucocorticoids, or placebo plus standard therapy. At week 76, obinutuzumab significantly increased rates of CRR compared with placebo (46.4% vs 33.1%; adjusted difference 13.4%; 95% CI, 2.0–24.8; 

= .0232), leading to its FDA approval for lupus nephritis in October 2025.

In a prespecified histologic substudy, 64 participants underwent paired baseline and post-week 76 kidney biopsies, and 29 provided additional tissue for B-cell and plasma cell analyses via a novel 5-plex immunofluorescence assay (CD79a, CD19, CD38, CD138, Ki67).

Histologic remission (activity index [AI]=0) and near-histologic remission (AI≤1) were achieved in 46.9% and 65.6% of obinutuzumab-treated patients versus 18.8% and 21.9% with placebo (adjusted differences 30.75% and 47.69%; 

= .0002, respectively). The mean reduction in AI was –5.0 (SD 4.7) for obinutuzumab versus –1.8 (SD 4.6) for placebo, while chronicity index changes were minimal in both arms.

Notably, more than half of obinutuzumab-treated patients who did not achieve clinical CRR still achieved histologic remission (AI=0), with a rate of 52.6% versus 8.3% among non-responders (adjusted difference 44.9%; 

=0.0018), which Rovin suggests is indicative of clinical endpoints underestimating tissue-level improvement.

Tissue-level biomarker data confirmed near-complete renal B-cell depletion with obinutuzumab (median change –98.3% from baseline), compared to a +29.8% increase with placebo. Plasma cell counts declined by 57.1% with obinutuzumab versus a +2.7% increase in the placebo arm, confirming deep immunologic inactivation within the kidney.

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

 include Alexion, Artiva, AstraZeneca/MedImmune, Aurinia Pharmaceuticals, Biogen Idec, Bristol Myers Squibb, Calliditas Therapeutics, Genentech/Hoffmann-La Roche, GSK, Omeros, Travere Therapeutics, and others.

Beyond Clinical Response in the REGENCY Trial: The Impact of Obinutuzumab on Histologic Remission in Patients with Active Lupus Nephritis. 

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

Genentech. FDA Approves Genentech’s Gazyva for the Treatment of Lupus Nephritis. October 20, 2025. Accessed October 20, 2025. 

https://www.businesswire.com/news/home/20251019548091/en/FDA-Approves-Genentechs-Gazyva-for-the-Treatment-of-Lupus-Nephritis

Discover groundbreaking insights on lupus nephritis treatment from the REGENCY trial, highlighting the impact of obintuzumab on patient outcomes.

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

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

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.

Shikha Wadhwani, MD, MS

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