Two-Year Results from a Randomized, Controlled Study of Obinutuzumab for Proliferative Lupus Nephritis

Richard Furie¹, Gustavo Aroca², Analia Alvarez³, Hilda Fragoso-Loyo⁴, Elizabeth Zuta Santillan⁵, Brad Rovin⁶, Paul Brunetta⁷, Thomas Schindler⁸, Imran Hassan⁹, Matthew Cascino¹⁰, Jay Garg¹⁰ and Ana Malvar¹¹, ¹Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, ²Simon Bolivar University y Clinica de la Costa, Barranquilla, Colombia, ³CEMIC, Buenos Aires, Argentina, ⁴Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, ⁵Instituto de Ginecología y Reproducción, Lima, Peru, ⁶The Ohio State University, Columbus, ⁷Genentech, Inc., South San Francisco, ⁸F. Hoffmann-La Roche Ltd., Basel, Switzerland, ⁹Hoffmann-La Roche Ltd, Mississauga, Canada, ¹⁰Genentech, Inc., South San Francisco, CA, ¹¹Organizacion Medica de Investigacion, Buenos Aires, Argentina

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, B-Lymphocyte, clinical trial, Lupus nephritis, Nephritis

Session Information

Date: Saturday, November 7, 2020

Title: SLE – Treatment (0985–0989)

Session Type: Abstract Session

Session Time: 3:00PM-3:50PM

Background/Purpose: NOBILITY demonstrated improved renal responses and complete B-cell depletion with the humanized type II anti-CD20 monoclonal antibody obinutuzumab (OBI) compared with placebo (PBO) through 18 months in patients with proliferative lupus nephritis (LN) when added to standard of care therapies [1]. Two-year results from NOBILITY are reported here.

Methods: Patients with class III/IV LN received mycophenolate and steroids and were randomized to blinded OBI or PBO infusions on weeks 0, 2, 24, and 26. The primary endpoint was complete renal response (CRR) at week 52. Patients were followed through week 104. Secondary endpoints included overall renal response (ORR) and modified CRR (mCRR). The prespecified alpha level was 0.2 and analyses after week 52 were exploratory.

Results: 125 patients were randomized and received blinded infusions; 102 patients (82%) completed 104 weeks of follow up. CRR was greater with OBI than PBO at week 52 (35% vs. 23%, P = 0.115), week 76 (40% vs. 18%, P = 0.007), and week 104 (41% vs 23%, P = 0.026; Table). At week 104, OBI patients had greater improvement in eGFR, UPCR, anti-dsDNA, C3, and C4. Fewer OBI patients required initiation of a new rescue therapy through week 104 (OBI 6, PBO 12). Peripheral B-cells were detected in 92% of OBI patients at week 104. Serious adverse events (OBI 25% vs. PBO 30%), serious infections (8% vs. 18%) and deaths (1 vs. 4) were not increased with OBI.

Conclusion: NOBILITY demonstrated a sustained benefit of OBI through week 104, approximately 18 months after the final OBI infusion. The OBI dosing regimen was associated with a return of peripheral B-cells by week 104. There were no unexpected safety findings. OBI use in LN will be further evaluated in the Phase 3 REGENCY trial.

References:
1. Rovin B, et al. ASN 2019 [abstract].

Table. Week 104 Results.

Disclosure: R. Furie, AstraZeneca/MedImmune, 2, 5; G. Aroca, None; A. Alvarez, None; H. Fragoso-Loyo, None; E. Zuta Santillan, None; B. Rovin, GSK, 1, Aurinia, 5, AstraZeneca, 5, Novartis, 5, Alexion, 5, Bristol-Myers Squibb, 5; P. Brunetta, Genentech, 9; T. Schindler, Roche, 1, 3; I. Hassan, Roche, 1, 3; M. Cascino, Genentech, 1, 3; J. Garg, Genentech, 1, 3; A. Malvar, None.

To cite this abstract in AMA style:

Furie R, Aroca G, Alvarez A, Fragoso-Loyo H, Zuta Santillan E, Rovin B, Brunetta P, Schindler T, Hassan I, Cascino M, Garg J, Malvar A. Two-Year Results from a Randomized, Controlled Study of Obinutuzumab for Proliferative Lupus Nephritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/two-year-results-from-a-randomized-controlled-study-of-obinutuzumab-for-proliferative-lupus-nephritis/. Accessed .

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