P019 Obinutuzumab demonstrates steroid-sparing effects and consistent benefit in patients with lupus nephritis when using multiple primary endpoint definitions: secondary analysis of the REGENCY trial results

Abstract Background/Aims The REGENCY trial (NCT04221477) demonstrated superiority of obinutuzumab (OBI) over placebo (PBO) in achieving complete renal response (CRR) when added to standard therapy (ST) in patients with lupus nephritis. These analyses evaluated OBI+ST vs PBO+ST across different renal response definitions from recent studies, the efficacy of OBI+ST vs PBO+ST on each component of the REGENCY CRR definition and the oral prednisone intake over time. Methods REGENCY, BLISS-LN and AURORA-1 renal response endpoint definitions were used for analysis of the REGENCY dataset at Week 76 (Table 1). The Cochran-Mantel-Haenszel test, stratified by region and race, was used for comparisons. All patients received oral prednisone as part of ST, tapered to 5 mg/day by Week 24. Results At week 76, 46.4% of patients in the OBI+ST (n = 135) and 33.1% in the PBO+ST arm (n = 136) achieved CRR (adjusted difference: 13.4%, 95% CI, 2.0 to 24.8%; P=0.0232). The proportions of OBI+ST vs PBO+ST achieving modified BLISS-LN primary efficacy renal response were 51.8% and 39.7% (adjusted difference: 12.1%, 95% CI, 0.5 to 23.8%; P=0.0432); modified BLISS-LN CRR were 48.7% and 33.1% (adjusted difference: 15.7%, 95% CI, 4.3 to 27.2%; P=0.0084); modified AURORA-1 CRR were 48.7% and 33.8% (adjusted difference: 15.0%, 95% CI, 3.6 to 26.5%; P=0.0117). More patients achieved the individual components of CRR at week 76 in the OBI vs PBO arm (UPCR 0.5 g/g: 47.4% vs 36.0%; eGFR ≥85% of baseline: 83.7% vs 75.7%; no occurrence of intercurrent events: 88.9% vs 75.0% for OBI+ST and PBO+ST, respectively). The main reasons for not attaining CRR were UPCR ≥0.5 or eGFR 85% of baseline (54.8% OBI+ST vs 65.4% PBO+ST). The mean daily prednisone intake was consistently lower in patients in the OBI vs PBO arm from week 24-76. A consistently higher proportion of patients in the OBI vs PBO arm achieved a daily prednisone (or equivalent) dose of ≤ 5 mg/day from week 36; absolute difference from week 64-76 (78.5% vs 68.4% for OBI+ST vs PBO+ST; adjusted difference 95% CI: 10.1% −0.5 to 20.4, P=0.0589). Conclusion OBI showed consistent benefit across patient subgroups utilising multiple alternative definitions of CRR and exhibited steroid-sparing properties. Disclosure B.H. Rovin: Other; B.H.R. has received consulting fees from F. Hoffmann-La Roche Ltd/Genentech Inc. J.P. Garg: Other; J.P.G is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. R.A. Furie: Other; R.A.F. has received research support and consulting fees from Chugai Pharmaceutical Co., Ltd., F. Hoffmann-La Roche Ltd, Genentech, Inc. and GlaxoSmithKline. R. Jones: Other; R.J. has received research support and/or consulting fees from F. Hoffmann-La Roche Ltd and CSL Vifor. A. Saxena: Other; A.S. has received research support and/or consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb, GlaxoSmithKline, Synthekine and UCB. P. Esposito: Other; P.E. has received fees for advisory activity from F. Hoffmann-La Roche Ltd and Sanofi. F.I. Palazuelos: Other; F.I.P. has received research support and/or consulting fees for Abbvie, Amgen, Eli Lilly, F. Hoffmann-La Roche Ltd, Janssen, Novartis, Pfizer and Takeda. E. Martins: Other; E.M. is an employee and shareholder of F. Hoffmann-La Roche Ltd. C. Petry: Other; C.P. is an employee and shareholder of F. Hoffmann-La Roche Ltd. N. Frey: Other; N.F. is an employee of F. Hoffmann- La Roche Ltd. B. Yoo: Other; B.Y. is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. I. Hassan: Other; I.H. is an employee of F. Hoffmann-La Roche Ltd. T. Schindler: Other; T.S. is an employee and shareholder of F. Hoffmann-La Roche Ltd. T.A. Omachi: Other; T.A.O. is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. W.F. Pendergraft: Other; W.F.P. is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. M.B. Santiago: None. G. Aroca-Martínez: None. A. Malvar: Other; A.M. has received consulting fees and/or reports professional services for Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Kezar, Novartis and Pfizer.