REGENCY: Obinutuzumab’s Deep B-Cell Depletion in Kidney Supports Benefit for Lupus Nephritis

Obinutuzumab (Gazyva; Genentech) extensively depleted B-cells and significantly reduced plasma cells in kidney tissue of patients with lupus nephritis (LN).1

These findings, from an exploratory kidney biopsy analysis of participants in the REGENCY trial (NCT04221477), were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Brad H. Rovin, MD, Lee A. Hebert Professor of Nephrology, Ohio State University Wexner Medical Center. Rovin also serves as Division Director of Nephrology and Medical Director of the Ohio State University Clinical Research Management Organization.

“In the REGENCY trial, addition of the type 2 anti-CD20 monoclonal antibody, obinutuzumab, to standard therapy (ST) in patients with active LN increased the proportion of complete renal responders at Week 76 compared with placebo plus ST,” Rovin and colleagues wrote.1 “Along with the superior clinical benefit, obinutuzumab treatment resulted in rapid, profound and sustained peripheral CD19+ B-cell depletion. It was hypothesized that in addition to complete peripheral B-cell depletion, obinutuzumab treatment would lead to deep depletion of B cells in the kidneys of patients with LN.”

Rovin and colleagues found that obinutuzumab treatment almost completely depleted B-cells at Week 76, with a −98.34% median percent change from baseline compared to a 29.8% median percent increase from baseline in the placebo arm. The adjusted mean reduction in B-cell counts at Week 76 was statistically superior compared to placebo (−16.6 cells/mm2, ANCOVA P<.0001) after adjusting for baseline B cell count variability.1

Furthermore, at Week 76, obinutuzumab treatment substantially reduced plasma cell counts in kidneys by a median percent reduction of 57.13% from baseline, compared to a 2.74% increase in the placebo arm. Obinutuzumab’s reduction compared to placebo’s increase was statistically significant (−19.2 cells/mm2, ANCOVA P = .0039) after adjusting for baseline plasma cell levels.1

“Obinutuzumab treatment resulted in complete/near complete depletion of B-cells and a significant reduction of plasma cells within the kidney tissue of patients with LN. This is the first demonstration of kidney tissue-level B-cell and plasma cell depletion by an anti-CD20 agent in any glomerular disease. These findings suggest that obinutuzumab attenuates intra-renal autoimmunity by eliminating intra-renal B cells and significantly reducing intra-renal plasma cells. This may contribute to greater renal responses and fewer LN flares observed in obinutuzumab-treated patients in the REGENCY trial,” Rovin and colleagues concluded.1

Obinutuzumab was approved for adults with LN receiving ST on October 20, 2025, based on positive results from the phase 2 NOBILITY and phase 3 REGENCY studies.2 Following 4 initial doses in the first year, obinutuzumab can be administered twice yearly, offering an effective and potentially more convenient treatment option than traditional targeted therapies.

REGENCY was conducted at centers in 15 countries and included 271 patients 18-75 years of age who met the ACR classification criteria for systemic lupus erythematosus and had active class III or IV LN with or without concomitant class V disease according to the classification of the International Society of Nephrology and the Renal Pathology Society. In the study, nearly half of the participants (46.4%) on obinutuzumab in combination with ST achieved a complete renal response compared to 33.1% on standard therapy alone. This was accompanied by clinically meaningful improvements in complement levels and reductions in anti-dsDNA, corticosteroid use, and proteinuria, all signaling improved disease control. The safety profile of obinutuzumab was consistent with the well-characterized profile observed in its hematology-oncology indications.2

References

1. Rovin BH, Martins E, Austin CD, et al. Obinutuzumab Leads to Deep B-Cell Depletion in the Kidney Parenchyma of Patients With Lupus Nephritis: An Exploratory Analysis of the REGENCY Trial. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB13

2. Brooks A. FDA Approves Obinutuzumab (Gazyva) for Lupus Nephritis. Article. HCPLive. October 20, 2025. https://www.hcplive.com/view/fda-approves-obinutuzumab-gazyva-for-lupus-nephritis