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Kidney Week

Abstract: TH-OR30

Kidney-Related Outcomes in Patients with Active Lupus Nephritis Treated with Obinutuzumab: A Post Hoc Analysis of the Phase 2 NOBILITY Trial

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Rovin, Brad H., Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, United States
  • Alfonso Ross Terres, Jorge, Genentech Inc, South San Francisco, California, United States
  • Giang, Sophia, Genentech Inc, South San Francisco, California, United States
  • Schindler, Thomas, F. Hoffman-La Roche Ltd, Basel, Switzerland
  • Turchetta, Armando, F. Hoffman-La Roche Ltd, Basel, Switzerland
  • Garg, Jay P., Genentech Inc, South San Francisco, California, United States
  • Furie, Richard, Northwell Health, Great Neck, New York, United States
  • Pendergraft, William Franklin, Genentech Inc, South San Francisco, California, United States
  • Malvar, Ana, Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina
Background

Preservation of long-term kidney function is a major therapeutic goal in lupus nephritis (LN). In the randomized, double-blind, placebo-controlled, Phase 2 NOBILITY trial (NCT02550652; PMID: 34615636), patients with proliferative LN receiving obinutuzumab with standard-of-care therapy showed clinically meaningful improvement in complete and overall renal responses at Weeks 52, 76 and 104 compared with those receiving placebo and standard-of-care therapy. We conducted a post hoc analysis of NOBILITY to assess kidney-related outcomes.

Methods

Cox regression analysis was conducted for the time to first kidney-related event (death, doubling of serum creatinine or treatment failure), LN flare and first 30% and 40% eGFR decline from baseline. The eGFR slope was assessed in a linear mixed-effects model.

Results

Obinutuzumab significantly reduced the risk of kidney-related events or death (HR, 0.40; 95% CI, 0.20 to 0.80), LN flare (HR, 0.43; 95% CI, 0.20 to 0.95) and first eGFR decline of 30% (HR, 0.20; 95% CI, 0.06 to 0.61) and 40% (HR, 0.09; 95% CI, 0.01 to 0.73) (Figure). Risk of sustained eGFR decline of 30% and 40% was numerically lower, and a significant difference in attenuation of eGFR slope decline was observed between patients receiving obinutuzumab and standard-of-care therapy and those receiving placebo and standard-of-care therapy (annual slope difference, 4.10 mL/min/year; 95% CI, 0.14 to 8.08).

Conclusion

Obinutuzumab, in addition to increasing the possibility of achieving a complete renal response, significantly reduced the risk of kidney-related events, eGFR decline, time to LN flare and eGFR slope decline in a post hoc analysis, suggesting that obinutuzumab in combination with standard-of-care therapy may positively impact kidney-related outcomes. Obinutuzumab is being evaluated in patients with active proliferative LN in the global registrational Phase 3 REGENCY trial (NCT04221477).

Funding

  • Commercial Support – This study was funded by Genentech, Inc., a member of the Roche Group. Editorial assistance was provided by Health Interactions, Inc., and funded by F. Hoffmann-La Roche Ltd.