E006 Kidney-related outcomes with obinutuzumab in patients with active lupus nephritis: a pre-specified exploratory analysis ofthe REGENCY trial

Abstract Background/Aims Lupus nephritis is the most common, severe, organ-threatening manifestation of systemic lupus erythematosus. The randomised, double-blind, placebo-controlled, Phase III REGENCY trial (NCT04221477) demonstrated superiority of obinutuzumab over placebo for achievement of complete renal response when added to standard therapy (mycophenolate mofetil plus glucocorticoids) in patients with active lupus nephritis. This study assessed the effects of obinutuzumab on time to lupus nephritis flare, time to an unfavourable kidney outcome and annualised estimated glomerular filtration rate (eGFR) slope during the REGENCY trial. Methods Time to lupus nephritis flare was assessed between Weeks 24 and 76 by Cox regression. The composite outcome of death, doubling of serum creatinine or treatment failure was defined as an unfavourable kidney outcome. Time to an unfavourable kidney outcome from baseline to Week 76 was also assessed by Cox regression after stratifying for race and region. Linear mixed-effects modelling was used to assess eGFR slope between Weeks 12 and 76. Analyses were not controlled for type I error. Results Between Weeks 24 and 76, the proportion of patients with lupus nephritis flare was lower in the obinutuzumab arm (11.1%) compared with the placebo arm (23.5%), with a hazard ratio of 0.44 (95% CI, 0.24 to 0.82; P=0.0074). The proportion of patients with unfavourable kidney outcomes in the obinutuzumab arm (8.10%) was also lower compared with the placebo arm (21.30%), with a hazard ratio of 0.37 (95% CI, 0.18 to 0.75; P=0.0039). Numerical attenuation of eGFR decline from Week 12 to Week 76 was observed in the obinutuzumab arm with the annualised eGFR slope calculated as − 0.71 (SE = 1.454) compared with −4.39 (SE = 1.454) in the placebo arm, with a difference in eGFR slope of 3.68 (SE = 2.055; P=0.0732), favouring obinutuzumab-treated patients (Table 1). Conclusion This pre-specified exploratory analysis of the REGENCY trial demonstrated that obinutuzumab significantly reduced the occurrence of lupus nephritis flares and unfavourable kidney outcomes and attenuated the annualised decline in kidney function compared with placebo-treated patients. Together with the significantly higher proportion of patients achieving a complete renal response in the obinutuzumab arm, these findings suggest that obinutuzumab affords long-term kidney survival benefits compared with standard therapy. Disclosure B.H. Rovin: Other; B.H.R has received consulting fees from F. Hoffmann-La Roche Ltd/Genentech, Inc. W.F. Pendergraft: Other; W.F.P. is an employee of Genentech, Inc., and shareholder of F. Hoffmann-La Roche Ltd. L. Lightstone: Other; L.L. reports consulting fees and/or services for Alexion, Argenx, AstraZeneca, Boehringer Ingelheim, Carna Health, F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Kezar, Nkarta, Novartis, Otsuka and Pfizer. E. Daugas: Other; E.D. has received consulting fees and/or support from Alexion, Amgen, AstraZeneca, CSL, GlaxoSmithKline, Novartis, Otsuka and Vifor. 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. T.A. Omachi: Other; T.A.O. 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. E. Martins: Other; E.M. is an employee and shareholder of F. Hoffmann-La Roche Ltd. T. Schindler: Other; T.S. is an employee and shareholder of F. Hoffmann-La Roche Ltd. J.P. Garg: Other; J.P.G. is an employee of Genentech, Inc., and shareholder of F. Hoffmann-La Roche Ltd. L.F. Quintana: Other; L.F.Q. has received consulting fees from Genentech, Inc., GlaxoSmithKline and Otsuka. P. Leszczyński: 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.