James Tumlin, MD, is the president of NephroNet, director of research at Georgia Nephrology, and a professor of medicine in nephrology at Emory University School of Medicine.

James Tumlin, MD

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

Povetacicept led to substantial, sustained UPCR reductions with stable eGFR, significant Gd-IgA1 reductions, hematuria resolution, clinical remission, with favorable safety in IgA nephropathy (IgAN) and primary membranous nephropathy (pMN).

These findings, from the phase 1/2 RUBY-3 trial, were presented at the 

American Society of Nephrology (ASN) Kidney Week 2025

, held November 5-9, 2025, in Houston, Texas, by James Tumlin, MD, Adjunct Professor, Department of Medicine, Emory University School of Medicine.

Povetacicept is designed to simultaneously inhibit BAFF and APRIL, two central cytokines that regulate pathogenic B-cell maturation, immunoglobulin class switching, plasma-cell survival, and downstream autoantibody production. Unlike agents that act downstream on inflammation or proteinuria, this approach aims to directly interrupt the causal biology driving Gd-IgA1 generation in IgAN and anti-PLA2R autoantibody production in pMN. The 48-week analyses from RUBY-3 provide the clearest evidence to date that these upstream immunologic effects translate into meaningful reductions in proteinuria and support the potential for disease-modifying impact.

Patients with IgAN receiving povetacicept 80 mg experienced a 64% mean reduction in 24-hour UPCR at week 48, with 65% achieving UPCR <0.5 g/g, stable eGFR, and early, deep, and sustained declines in circulating Gd-IgA1 (77% by week 48). Hematuria resolved in 90% and more than half reached clinical remission. In people with pMN, the same dose achieved an 82% reduction in UPCR, durable stabilization of kidney function, and 83% reductions in anti-PLA2R autoantibodies, with 100% of patients in immunologic remission and universal achievement of partial remission.

 spoke with Tumlin to discuss how dual BAFF/APRIL inhibition reshapes disease biology in IgAN and pMN, what the 48-week kinetics suggest about long-term remission potential, and how these findings may influence future treatment sequencing in immune-complex glomerular disease.

Across both diseases, povetacicept was generally well tolerated, with decreases in IgG monitored but not associated with serious infections or clinically significant immune compromise. Tumlin emphasized that these characteristics underscore its promise as a disease-modifying therapy, distinct from hemodynamic or anti-proteinuric approaches.

"I think, looking forward ahead, the APRIL/BAFFS may be able to induce a more long and sustained remission. Don't know that yet, but that's data that will be evolved and gleaned out over time," Tumlin said.

Disclosures for Tumlin include Vera Therapeutics, Calliditas Therapeutics, Alexios Pharmaceuticals, and Vertex Pharmaceuticals.

Tumlin JA, Yalavarthy R, Kim DK, et al. Efficacy and Safety of Povetacicept in Patients with IgAN and Primary Membranous Nephropathy (pMN) at 48 Weeks of Treatment: The RUBY-3 Study. Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025. #SA-OR091

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Tumlin discussed improvements in UPCR and Gd-IgA1 seen with povetacicept.

Sparsentan and Progression to Kidney Failure in FSGS, with James Tumlin, MD

Findings from a posthoc analysis of the phase 3 DUPLEX study of sparsentan (Filspari) are providing new insight into the dual endothelin angiotensin receptor antagonist’s nephroprotective benefit in patients with 

focal segmental glomerulosclerosis (FSGS)

The data were presented during a late-breaking session at the National Kidney Foundation (NKF) Spring Clinical Meetings 2025 in Boston, Massachusetts, and showed patients with FSGS treated with sparsentan achieved partial and complete remission more rapidly and with higher incidence than those treated with irbesartan. Additionally, patients who reached partial or complete remission showed a markedly reduced risk of progression to kidney failure versus those who did not.

“A substantial number of people have very few options. Prednisone is really not used by most anyone today, certainly not by me,” James Tumlin, MD, president of NephroNet, director of research at Georgia Nephrology, and a professor of medicine in nephrology at Emory University School of Medicine, explained to 

. “CNIs, tacrolimus, and cyclophosphamide are still used, but you still have the same problem with long-term toxicity… We've been desirous of having a new type of therapeutic pathway for quite some time.”

Sparsentan may be poised to address this unmet need in FSGS – in March 2025, Travere Therapeutics submitted a supplemental New Drug Application to the US Food and Drug Administration seeking priority review for traditional approval of sparsentan for the treatment of FSGS, supported by results from the phase 3 DUPLEX study and the phase 2 DUET study.

A multicenter, double-blind, active-controlled trial, DUPLEX enrolled 371 patients 8-75 years of age with biopsy-confirmed FSGS or a documented pathogenic variant in a podocyte protein associated with FSGS, a urinary protein-to-creatinine ratio ≥ 1.5, and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 of body-surface area at screening.

Following randomization in a 1:1 ratio, 184 participants were randomly assigned to sparsentan and 187 were randomly assigned to irbesartan. Results showed there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan.

In the posthoc analysis presented at NKF, investigators investigated the impact of sparsentan versus irbesartan on partial or complete remission of proteinuria and the effect of achieving these thresholds on progression to kidney failure.

Results showed both partial remission and complete remission were achieved more frequently with sparsentan than with irbesartan:

Partial remission: 64.7% vs 43.9% (relative risk [RR], 1.48; 95% CI, 1.23-1.78)

Complete remission: 18.5% vs 7.5% (RR, 2.47; 95% CI, 1.37-4.45)

Additionally, investigators noted partial and complete remission were achieved earlier with sparsentan than with irbesartan.

Of note, irrespective of treatment group, lowering proteinuria to reach partial and complete remission resulted in a marked reduction in progression to kidney failure. For partial remission the odds of progressing to kidney failure were 3% compared with 15.9% without partial remission. For complete remission, the odds of progressing to kidney failure were 2.1% compared with 9.9% without complete remission.

“Those numbers seem similar, but there's a really important point behind that, which is that even a partial reduction in proteinuria has resulted in a profound reduction in the risk of progression of renal disease,” Tumlin explained. “From my standpoint, I think this will be a significant weapon in the argument to change the accepted clinical endpoints for drug development. I suspect that drug development FSGS will explode if that ruling goes through by the FDA.”

Editors’ note: Tumlin has relevant disclosures with Aurinia Pharmaceuticals, Biogen, Mallinckrodt, Novartis, Vertex Pharmaceuticals, and others.

Tumlin J, Tesar V, Trimarchi H, et al. Patients (Pts) in DUPLEX Achieved Partial or Complete Remission of Proteinuria Earlier and More Often With Sparsentan (SPAR) vs Irbesartan (IRB): Implications for Slowing Progression to Kidney Failure (KF) in Focal Segmental Glomerulosclerosis (FSGS). Abstract presented at: National Kidney Foundation Spring Clinical Meetings 2025. Boston, MA. April 9 - 13, 2025.

Brooks A. Travere Therapeutics Submits sNDA for Sparsentan (Filspari) in FSGS. 

. March 17, 2025. Accessed April 14, 2025. 

https://www.hcplive.com/view/travere-therapeutics-submits-snda-sparsentan-filspari-fsgs

Campbell P. Sparsentan Use Could Lower Risk of Kidney Failure, Death in FSGS. HCPLive. November 3, 2023. Accessed April 14, 2025. 

https://www.hcplive.com/view/sparsentan-use-could-lower-risk-of-kidney-failure-death-in-fsgs

Tumlin reviews findings from a posthoc analysis of DUPLEX demonstrating sparsentan’s impact on partial remission, complete remission, and kidney failure.

James Tumlin, MD

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