POS0529 OBINUTUZUMAB BENEFITS PATIENTS WITH ACTIVE LUPUS NEPHRITIS IRRESPECTIVE OF BASELINE PROTEINURIA SEVERITY: A POST HOC ANALYSIS OF THE PHASE II NOBILITY TRIAL
Authors: R. A. Furie, J. A. Ross Terres, E. Martins, I. Hassan, T. Schindler, J. P. Garg, W. F. Pendergraft, A. Malvar, B. H. Rovin
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Lupus nephritis (LN) is the most common severe organ-threatening manifestation of systemic lupus erythematosus. The randomized, placebo-controlled, Phase II NOBILITY trial (NCT02550652) demonstrated superiority of obinutuzumab over placebo for achievement of complete and overall renal responses at Week 52 when added to standard-of-care mycophenolate mofetil and corticosteroids in patients with proliferative LN.<sup>1</sup> Recent and ongoing registrational clinical trials in LN use composite primary endpoints driven primarily by reduction in proteinuria. Resolution of proteinuria after new-onset LN or LN flare positively influences long-term kidney health. <h3>Objectives:</h3> To assess the achievement of complete renal response (CRR) in participants from the NOBILITY trial using primary endpoint definitions from the ongoing REGENCY and completed BLISS-LN<sup>2</sup> trials and to evaluate effect of proteinuria at baseline on achieving the REGENCY CRR. <h3>Methods:</h3> Primary and modified primary endpoints from the Phase III REGENCY trial (NCT04221477) and a modified primary endpoint from the Phase III BLISS-LN trial<sup>2</sup> (NCT01639339) were used for this analysis at Weeks 52, 76 and 104. Endpoint measures were defined as follows: REGENCY CRR (estimated glomerular filtration rate [eGFR] ≥85% of baseline, urine protein-creatinine ratio [UPCR] ≤0.5 g/g and no treatment failure or rescue therapy), modified REGENCY CRR (eGFR ≥85% of baseline eGFR, UPCR ≤0.7 g/g and no treatment failure or rescue therapy) and modified BLISS-LN primary efficacy renal response (PERR; eGFR ≥80% of baseline eGFR or eGFR ≥60 mL/min, UPCR ≤0.7 g/g and no treatment failure or rescue therapy). Subgroup efficacy analyses were performed by baseline UPCR &lt;2 vs ≥2 g/g and &lt;3 vs ≥3 g/g. Cochran-Mantel-Haenszel test stratified for region (US vs non-US) and race (Afro-Caribbean/African American vs others) was used to compare the CRRs between the treatment arms. All patients met the American College of Rheumatology classification criteria for systemic lupus erythematosus and had biopsy-proven proliferative LN. <h3>Results:</h3> Obinutuzumab with standard-of-care therapy was significantly superior compared with placebo with standard-of-care therapy when using the REGENCY CRR definition with the existing UPCR ≤0.5 g/g or with the modified UPCR cutoff of ≤0.7 g/g at Weeks 76 and 104 as well as the BLISS-LN PERR definition at Week 104 (Figure 1). In addition, the statistically significant effect of obinutuzumab with standard-of-care therapy compared with placebo with standard-of-care therapy was observed irrespective of baseline proteinuria levels (Figure 2). <h3>Conclusion:</h3> Obinutuzumab effects, in combination with standard-of-care therapy, persisted using the REGENCY and BLISS-LN primary endpoint definitions and may also positively impact patients with LN irrespective of baseline proteinuria levels. Obinutuzumab is currently undergoing further evaluation in patients with active proliferative LN in the global, registrational, Phase III REGENCY trial (NCT04221477). <h3>REFERENCES:</h3> [1] Furie RA, et al. <i>Ann Rheum Dis</i>. 2022;81:100-107. [2] Furie RA, et al. <i>N Engl J Med</i>. 2020;383(12):1117-1128. <h3>Acknowledgements:</h3> Funding provided by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Nucleus Global and funded by F. Hoffmann-La Roche Ltd. <h3>Disclosure of Interests:</h3> Richard A. Furie has received consulting fees from Genentech, Inc, and research support from Genentech, Inc, Jorge A. Ross Terres is a shareholder of F. Hoffmann-La Roche Ltd, and an employee of Genentech, Inc., Elsa Martins is an employee of F. Hoffmann-La Roche Ltd, Imran Hassan is a shareholder of F. Hoffmann-La Roche Ltd, and an employee of F. Hoffmann-La Roche Ltd, Thomas Schindler is a shareholder of F. Hoffmann-La Roche Ltd, and an employee of F. Hoffmann-La Roche Ltd, Jay P. Garg is a shareholder of F. Hoffmann-La Roche Ltd, and an employee of Genentech, Inc., William F. Pendergraft III is a shareholder of F. Hoffmann-La Roche Ltd, and an employee of Genentech, Inc., Ana Malvar has received consulting fees from Genentech, Inc., and F. Hoffmann-La Roche Ltd, Brad H. Rovin has received consulting fees from Genentech, Inc., and F. Hoffmann-La Roche Ltd.