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FDA Approves Obinutuzumab for Lupus Nephritis

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In October 2025, the U.S. Food & Drug Administration (FDA) approved obinutuzumab (Gazyva) for the treatment of adults with lupus nephritis who are receiving standard therapy.1

In November 2013, the FDA initially approved obinutuzumab for the treatment of patients with untreated chronic lymphocytic leukemia in combination with chlorambucil.2 The agent later gained FDA approval for the treatment of patients with different stages of follicular lymphoma. It attaches to CD20 found on certain types of B cells to reduce inflammation by targeting and depleting these disease-causing B cells.3

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In patients with lupus nephritis, obinutuzumab is administered as a 1,000 mg intravenous infusion. The first infusion is given over two days to minimize infusion reactions and hypersensitivity. The infusion process takes many hours, depending on patient response. Premedication with corticosteroids, acetaminophen and antihistamines is part of the regimen to reduce infusion-related reactions. The FDA has also approved a shorter, 90-minute infusion time for obinutuzumab that can be administered after the first infusion to eligible patients with lupus.1

The Research

This FDA approval is based on positive results from the NOBILITY (NCT02550652) and REGENCY (NCT04221477) clinical trials.4-7

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The phase 2, NOBILITY trial enrolled patients (N=125) with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative class III or IV lupus nephritis, with or without class V. Study patients were randomized to receive either obinutuzumab or placebo. The primary end point of complete renal response at week 52 was met by patients who received obinutuzumab in combination with standard therapy (i.e., mycophenolate mofetil or mycophenolic acid and corticosteroids), demonstrating superiority to placebo plus standard of care.7

Patients treated with obinutuzumab had increasing rates of complete renal response from week 52–76. At week 72, 40% of patients who received obinutuzumab achieved a complete renal response compared with 18% of patients who received placebo (P=0.007). Additionally, patients who received obinutuzumab met key secondary efficacy end points, showing improved overall renal response—either complete or partial renal responses—and serologic markers of disease activity. (Note: Based on data from the NOBILITY study, the FDA granted obinutuzumab a breakthrough therapy designation in 2019.8)

The phase 3, REGENCY trial enrolled patients (N=271) with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative class III or IV lupus nephritis, with or without class V. Patients were randomized in a 1:1 ratio to receive obinutuzumab or placebo. Almost half of the participants (46.4%) who received obinutuzumab in combination with standard therapy achieved a complete renal response compared with 33.1% of those who received placebo plus standard therapy.6 Clinically meaningful improvements in complement levels and reductions in anti-dsDNA, corticosteroid use and proteinuria were also observed. No new safety signals were identified during this study.

On the Horizon

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recently issued a positive opinion, recommending the approval of obinutuzumab for the treatment of adults with active lupus nephritis. A final decision from the European Commission is expected soon.8

Obinutuzumab is under clinical investigation for the treatment of patients with systemic lupus erythematosus, idiopathic nephrotic syndrome and membranous nephropathy, as well as in children and adolescents with lupus nephritis.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Hospital-Lower Manhattan.

References

  1. Supplemental biologics license approval letter: Gazyva (obinutuzumab) injection. U.S. Food & Drug Administration. 2025 Oct 17.
  2. Biologics license application approval letter: Gazyva (obinutuzumab). U.S. Food & Drug Administration. 2013 Nov 1.
  3. Highlights of prescribing information: Gazyva (obinutuzumab) injection. U.S. Food & Drug Administration. 2022 Jul 27.
  4. Genentech’s Gazyva (obinutuzumab), in combination with standard of care, more than doubles the percentage of lupus nephritis patients achieving complete renal response, compared to standard of care alone [news release]. Genentech Inc. 2019 Nov 9.
  5. A study to evaluate the safety and efficacy of obinutuzumab compared with placebo in participants with lupus nephritis [NCT02550652]. ClinicalTrials.org. 2024 Aug 27.
  6. A study to evaluate the efficacy and safety of obinutuzumab in patients with ISN/RPS 2003 class III or IV lupus nephritis (REGENCY) [NCT04221477]. ClinicalTrials.org. 2025 Nov 6.
  7. Furie R, Aroca G, Alvarez A, et al. A phase ii randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of obinutuzumab or placebo in combination with mycophenolate mofetil in patients with active class III or IV lupus nephritis [abstract 939]. Arthritis Rheumatol. 2019 Oct; 71(suppl 10).
  8. FDA approves Genentech’s Gazyva for the treatment of lupus nephritis [news release]. Business Wire. 2025 Oct 20.