Nephritis in Active Lupus: Gazyva’s Superiority Proven in NEJM Dat
Genentech, a member of the Roche Group, announced that a detailed analysis of its Phase III REGENCY trial of Gazyva® (obinutuzumab) in patients with active lupus nephritis (LN) has been published in the New England Journal of Medicine. The trial found a significant and clinically meaningful improvement in the primary endpoint of complete renal response (CRR). After 76 weeks, 46.4% of patients treated with Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved CRR, compared to 33.1% of those on standard therapy alone (adjusted difference 13.4%, 95% CI 2.0%-24.8%; p=0.0232). Additionally, patients on Gazyva showed meaningful improvements in complement levels and reductions in anti-dsDNA, indicating a reduction in disease activity and inflammation.
Genentech, a member of the Roche Group, has shared promising data from the Phase III REGENCY trial of Gazyva® (obinutuzumab) for treating active lupus nephritis (LN), which was presented at the World Congress of Nephrology (WCN) 2025 and submitted to regulatory authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The trial revealed that Gazyva, in combination with standard therapy, significantly improved outcomes in people with active lupus nephritis compared to standard therapy alone.
Dr. Levi Garraway, Chief Medical Officer and Head of Global Product Development at Genentech, highlighted that nearly half of lupus nephritis patients treated with Gazyva achieved a complete renal response (CRR), underscoring the treatment’s superiority over standard therapies. He emphasized the significant need for more effective treatments, especially for younger women and women of color, who are disproportionately affected by lupus nephritis and its progression to end-stage kidney disease. “Our goal is to address this urgent need by providing a more effective treatment option,” said Garraway.
Dr. Richard Furie, Chief of Rheumatology at Northwell Health, also praised the results, noting that the REGENCY trial confirmed earlier findings showing that obinutuzumab, which targets B cells, provided better outcomes for lupus nephritis patients than standard treatments alone. Additionally, Furie pointed out that patients receiving Gazyva were not only more likely to achieve the desired results, but were also able to reduce their corticosteroid use, which is a critical aspect of treatment for this condition.
The safety profile of Gazyva in the REGENCY trial was consistent with its established use in hematology-oncology indications. Key secondary endpoints showed that patients who received Gazyva plus standard therapy had a higher likelihood of achieving CRR, including a successful reduction in corticosteroid use compared to those on standard therapy alone. At week 76, 42.7% of patients in the Gazyva group achieved CRR with a prednisone taper, compared to 30.9% of those in the placebo group. Additionally, 55.5% of patients receiving Gazyva showed improvement in proteinuric response at week 76, compared to 41.9% in the placebo group. These findings are important as they suggest better disease control in lupus nephritis.
Moreover, Gazyva treatment resulted in a significant reduction in death or renal-related events through week 76. Specifically, 18.9% of patients in the Gazyva group experienced renal-related events, compared to 35.6% in the placebo group (p=0.0026). This reduction in renal complications is critical for improving long-term kidney function and overall patient survival.
The study also showed that Gazyva provided a benefit across a variety of patient subgroups, including those with more active lupus nephritis or higher levels of baseline proteinuria, further indicating its broad applicability for patients with varying disease severities.
The REGENCY trial was a randomized, double-blind, placebo-controlled study that enrolled 271 patients with proliferative Class III or IV lupus nephritis, with or without Class V involvement. Participants were randomly assigned to receive biannual intravenous doses of Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) or placebo plus standard therapy. The trial design was based on promising Phase II data and conducted during the COVID-19 pandemic.
Lupus nephritis is a potentially life-threatening condition caused by systemic lupus erythematosus (SLE), an autoimmune disease that commonly affects the kidneys. Approximately 1.7 million people worldwide are affected by lupus nephritis, with a higher prevalence in women, particularly women of color and those of childbearing age. Despite existing treatments, up to a third of lupus nephritis patients develop end-stage kidney disease within 10 years, requiring dialysis or kidney transplants.
Gazyva (obinutuzumab) is a humanized monoclonal antibody that targets CD20, a protein found on B cells that contribute to the disease. By depleting these B cells, Gazyva helps reduce inflammation and kidney damage, potentially delaying the progression to end-stage kidney disease. It is the only anti-CD20 monoclonal antibody to demonstrate CRR benefits in a Phase III lupus nephritis trial. Gazyva was granted Breakthrough Therapy Designation by the FDA in 2019 based on earlier promising data from the Phase II NOBILITY study. In addition to lupus nephritis, Gazyva is being studied in other kidney conditions, including membranous nephropathy and childhood-onset nephrotic syndrome, as well as in systemic lupus erythematosus (SLE), a broader autoimmune disease that often affects the kidneys.
In summary, Gazyva has demonstrated significant benefits in improving renal outcomes for patients with active lupus nephritis, offering a potential new treatment option for a patient population with limited options and high unmet needs. These findings mark a critical step toward improving disease management and outcomes for lupus nephritis patients.
