Obinutuzumab Reduces Urinary Biomarkers of Lupus in Phase 2 NOBILITY Analysis

A secondary analysis of the NOBILITY trial is offering clinicians further insight into the safety and efficacy of obinutuzumab (Gazya/Gazyvaro) among patients with lupus nephritis (LN).

The posthoc analysis, which was presented at the 62nd European Renal Association (ERA 2025) Congress, the study details the effects of obinutuzumab use relative to placebo therapy on urinary renal biomarker, with results demonstrating obinutuzumab was associated with improvements in a slew of markers for disease and disease progression.

“These findings suggest a mechanistic hypothesis whereby [obinutuzumab] modulates the kidney inflammatory microenvironment to promote repair and protect the parenchyma and long-term function, reinforcing its potential as a promising therapy for patients with LN; and urine biomarkers may offer early insights into treatment responses and warrant further investigation in larger studies for potential use in therapeutic response monitoring,” wrote investigators.

The phase 2 NOBILITY trial was a randomized, double-blind, placebo-controlled study assessing the safety and efficacy of obinutuzumab in combination with mycophenolate mofetil among 125 patients. The original trial results were presented at the American College of Rheumatology 2019 annual meeting by Richard Furie, MD, of Northwell Health. The trial’s primary endpoint was Results indicated 34.9% of patients achieved the primary endpoint in the obinutuzumab group compared to 22.6% of the placebo group, but this failed to reach the threshold for statistical significance (12.3% delta; 80% CI 2.1% to 22.6%; P = .115).

In February 2025, the field received news the phase 3 REGENCY trial, which examined obinutuzumab in addition to standard of care therapy against placebo. In this trial,46.4% of patients using obinutuzumab achieved a complete renal response, which was defined as and represents a 13.4% adjusted difference relative to standard of care therapy alone.

At ERA 2025, an international team of investigators led by Juan Manuel Mejía Vilet, MD, MSc, PhD, of the National Institutes of Medical Sciences and Nutrition in Mexico, presented data from an analysis examining the effect of the agent on renal biomarkers from the study. Per trial protocol, urine samples were analyzed using ELLA immunoassays and urine biomarker concentrations were normalized to urine creatinine and were analyzed using mixed models for repeated measures. Of note, the models used in the study were built to account for each patient, visit, treatment received, and baseline UPCR category.

Results of this latest analysis indicated use of obinutuzumab was associated with significantly greater reductions in urine CCL2, KIM1 and sCD163 and increases in urine EGF were observed relative to placebo therapy. Additionally, investigators pointed out there was a rapid and significantly greater decline in urine CCL2 and KIM1 levels were observed as early as week 12 and week 24, respectively, in the obinutuzumab group compared with the placebo group. Investigators also highlighted the presence of increased EGFR levels.

Further analysis revealed patients achieving complete renal response at week 52 had significantly greater decreases in urine CCL2, KIM1, and sCD163 and increases in urine EGF were observed at week 12 and persisting through week 76.

“Exploratory analyses from the Phase II NOBILITY study showed that OBI may induce early beneficial effects on kidney inflammation and damage markers in LN, as evidenced by reduced urine CCL2, KIM1 and sCD163 and increased urine EGF. Importantly, these urinary changes occurred within 24 weeks of [obinutuzumab] initiation (later for sCD163), preceding improvements in UPCR observed at Week 52,” investigators concluded.

References:

1. Meija-Vilet JM, Clarke HJ, Lanza B, et al. EFFECTS OF OBINUTUZUMAB ON URINARY RENAL BIOMARKERS IN LUPUS NEPHRITIS: A POST HOC EXPLORATORY ANALYSIS OF THE PHASE II NOBILITY STUDY. June 05, 2025. Accessed: June 05, 2025. Presented at the 62nd European Renal Association Congress in Vienna, Austria.

2. Campbell P. Obinutuzumab for Treatment of Lupus Nephritis Shows Promise in Phase 2 Trial. HCP Live. Published November 14, 2019. Accessed June 5, 2025. https://www.hcplive.com/view/obinutuzumab-for-lupus-nephritis-phase-2-trial

3. Campbell P. REGENCY: Obinutuzumab Proves Efficacy in Lupus Nephritis. HCP Live. Published February 7, 2025. Accessed June 5, 2025. https://www.hcplive.com/view/regency-obinutuzumab-proves-efficacy-in-lupus-nephritis