Brad Rovin, MD

Welcome to Kidney Compass: Navigating Clinical Trials!

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

Kidney Compass: Navigating Clinical Trials

, 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 

American Society of Nephrology (ASN) Kidney Week 2025

, 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

Podcasts

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

future of IgAN treatment, highlighting the BlyS/APRIL axis.

The Future of IgA Nephropathy Treatment

This is a video synopsis/summary of a panel discussion involving Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD.

In this discussion, Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD anticipate the imminent release of phase three data for drugs targeting the BAFF (B-cell activating factor) and APRIL (A proliferation-inducing ligand) axis, particularly April only and April and BAFF approaches. They foresee the potential availability of these drugs on the market within the next 24 months if they prove effective and gain approval.

The conversation shifts to safety concerns, emphasizing the favorable risk profile regarding hypogammaglobulinemia and infections associated with BAFF and APRIL inhibitors. Notably, the discussion touches on the crucial issue of vaccine responsiveness, highlighting preliminary data suggesting a less pronounced negative impact on vaccine responses compared to CD20-depleting therapies, especially relevant during the COVID-19 pandemic.

Dr Barratt concludes by urging viewers to keep a close eye on developments in the BAFF/APRIL axis, predicting its integration into the daily practice of healthcare professionals specializing in kidney diseases. He highlights the excitement surrounding established drugs like sibeprenlimab and atacicept, as well as promising newcomers like povetacicept, encouraging viewers to stay informed about forthcoming clinical data in this rapidly evolving field.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Videos

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the future of IgAN treatment, highlighting the BlyS/APRIL axis.

clinical trial data regarding the use of povetacicept for the treatment of IgAN.

Use of Povetacicept in Treatment of IgA Nephropathy

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the latest data on drugs targeting the B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) axis in IgA nephropathy (IgAN), presented at the American Society of Nephrology (ASN) meeting. The conversation highlights the growing interest and excitement in the nephrology community about these emerging therapies.

Dr Barratt mentions recent data on sibeprenlimab and povetacicept and emphasizes the significant attention these drugs received at the ASN meeting. He specifically discusses the promising results from sibeprenlimab, showcasing consistent and effective APRIL inhibition, resulting in a reduction in galactose-deficient IgA1 (Gd-IgA1) and translation to reduced proteinuria.

Dr Rovin provides insights into the presentation of data on povetacicept, emphasizing its impressive proteinuria reduction, even at what is referred to as a "low dose." Both experts acknowledge the need for further dose-ranging studies to determine optimal dosing.

The discussion extends to the potential applications of these drugs beyond IgAN. Dr Barratt highlights a patient with membranous nephropathy treated with povetacicept, showing a significant reduction in anti-PLA2R titers, suggesting a potential broader impact on autoantibody-mediated diseases.

The experts discuss the ability of these drugs to target different cell populations, providing a unique advantage in diseases where both pathogenic antibodies and autoantibodies play a role. Dr Barratt emphasizes the potential benefits in lupus, envisioning combined approaches with BAFF and APRIL inhibition.

Dr Rovin concludes by expressing excitement about the multifaceted applications of these drugs in various diseases and suggests rethinking the use of immunosuppression, aiming for effective treatment with reduced overt immunosuppression. The conversation underscores the transformative potential of BAFF and APRIL inhibitors in reshaping the landscape of nephrology therapeutics across multiple diseases.

Drs Jonathan Barratt and Brad Rovin comment on clinical trial data regarding the use of povetacicept for the treatment of IgAN.

review clinical trials for new and emerging treatments for IgAN, highlighting atacicept and telitacicept.

Clinical Trial Results From Emerging Therapies in IgA Nephropathy

The discussion shifts to the emerging class of drugs targeting the B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) axis in IgA nephropathy (IgAN). Dr Barratt prompts Dr Rovin to share his impressions from a high-level perspective on these new therapeutics, considering the variety of drugs available, such as APRIL-only therapeutics, zigakibart, sibeprenlimab, and combinations of BAFF and APRIL inhibitors.

Dr Rovin acknowledges the challenge of assessing these drugs collectively due to variations in patient populations and study phases. However, he notes that the aggregate data suggests a beneficial effect from targeting both cytokines. His primary considerations in evaluating these drugs include efficacy, convenience, adherence, and side-effect profiles.

Dr Barratt shares his optimism about this therapeutic pathway, foreseeing its fundamental role in IgAN and its potential extension to other disease areas. He emphasizes the promising concordance in side-effect profiles and the anticipated ability to modulate these cells safely and effectively. Dr Rovin expresses agreement and expands the discussion to the broader implications of this therapeutic approach. He envisions applications beyond IgAN, including lupus and membranous nephropathy, suggesting a shift towards considering glomerular diseases as a whole rather than isolated entities. Both experts highlight the need for innovative trial designs, drawing parallels with basket trials in oncology, to explore shared pathways across various nephrological conditions, particularly in the context of rare diseases.

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, review clinical trials for new and emerging treatments for IgAN, highlighting atacicept and telitacicept.

Brad Rovin, MD

Articles