Feinstein Researchers Lead Breakthrough Study for Lupus Kidney Disease
In a significant breakthrough for autoimmune disease treatment, researchers at Northwell Health’s Feinstein Institutes for Medical Research have reported encouraging results from a global Phase 3 clinical trial evaluating the use of obinutuzumab in patients with lupus nephritis, a serious and potentially life-threatening manifestation of systemic lupus erythematosus (SLE). The findings, published in The New England Journal of Medicine, suggest that obinutuzumab, an anti-CD20 monoclonal antibody currently approved for B cell malignancies, may substantially improve renal outcomes when added to conventional immunosuppressive therapy.
The study was spearheaded by Richard A. Furie, MD, Professor at the Institute of Molecular Medicine at the Feinstein Institutes, and holder of The Marilyn and Barry Rubenstein Chair in Rheumatology. Dr. Furie, who also serves as Chief of the Division of Rheumatology at Northwell Health, has long been at the forefront of lupus research and treatment innovation. His latest work underscores the potential to repurpose a well-characterized oncology drug for use in autoimmune nephrology, addressing an urgent unmet need in lupus care.
Understanding the Burden of Lupus Nephritis
Systemic lupus erythematosus is a chronic autoimmune disorder characterized by aberrant immune system activity that results in widespread inflammation and tissue damage in multiple organ systems. Among the most severe and debilitating complications of lupus is lupus nephritis—a condition marked by inflammation of the kidneys that can progress to end-stage renal disease (ESRD) if inadequately managed. Lupus nephritis occurs in approximately 40% to 60% of individuals with SLE and disproportionately affects young women and people of color, particularly those of African American, Hispanic, and Asian descent.
Current standard-of-care therapies for lupus nephritis generally include immunosuppressive agents such as mycophenolate mofetil (MMF), cyclophosphamide, and corticosteroids like prednisone. While these treatments can be effective, many patients experience suboptimal responses, relapse, or intolerable side effects. There is an urgent clinical need for additional therapeutic options that can induce durable remission and preserve long-term renal function.
The REGENCY Trial: Design and Rationale
To explore new frontiers in lupus nephritis management, the REGENCY trial was launched as a rigorous, randomized, double-blind, placebo-controlled Phase 3 study. Conducted across 15 countries and involving 271 adult participants, the trial specifically enrolled patients with biopsy-confirmed active lupus nephritis. This critical inclusion criterion ensured that the study population reflected the clinical reality of severe disease requiring aggressive immunosuppression.
Participants were randomized to receive either obinutuzumab or placebo, both administered in conjunction with standard background therapy consisting of mycophenolate mofetil and glucocorticoids. The primary endpoint of the trial was the proportion of patients achieving a complete renal response at Week 104—a stringent composite outcome that typically includes normalization of serum creatinine, urine protein-to-creatinine ratio, and inactive urinary sediment, along with adherence to low-dose corticosteroid regimens.
Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody designed to induce more potent B cell depletion compared to earlier-generation agents such as rituximab. By targeting CD20-expressing B cells, obinutuzumab effectively dampens the autoimmune cascade that underpins lupus pathophysiology.
Key Findings and Clinical Impact
Results from the REGENCY trial demonstrated a statistically and clinically significant improvement in renal outcomes among patients receiving obinutuzumab compared to those in the placebo arm. Specifically, a greater percentage of participants in the obinutuzumab group achieved complete renal response, highlighting the therapeutic antibody’s ability to enhance remission rates when used alongside standard immunosuppressive agents.
“The results from REGENCY represent a major step forward in the treatment landscape for lupus nephritis,” said Dr. Furie. “The fact that obinutuzumab is already an approved, accessible medication with a known safety profile makes these findings particularly exciting for clinicians and patients alike. We now have strong evidence that augmenting current therapies with this B cell–targeted agent can yield meaningful benefits in renal health.”
Beyond efficacy, the safety profile of obinutuzumab in the trial was consistent with previous data from its use in hematologic malignancies, and no new safety signals emerged. Importantly, the addition of obinutuzumab did not significantly increase the incidence of serious adverse events, suggesting a favorable risk-benefit ratio in the lupus nephritis setting.
A Paradigm Shift in Autoimmune Therapeutics
The REGENCY trial findings build on a growing body of evidence supporting B cell depletion as a viable therapeutic strategy in autoimmune diseases. Unlike rituximab, which has shown mixed results in prior lupus nephritis trials, obinutuzumab may provide more consistent B cell elimination due to its optimized Fc engineering and enhanced antibody-dependent cellular cytotoxicity (ADCC). These pharmacological advantages may translate into more robust and sustained immunologic control.
Kevin J. Tracey, MD, President and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research, emphasized the significance of this work in advancing translational science. “Dr. Furie and his colleagues have delivered a vital breakthrough for patients with lupus nephritis, an area of medicine where effective treatments are in critically short supply,” said Dr. Tracey. “This trial demonstrates not only short-term improvements in renal response but also opens the door for longer-term studies to assess whether obinutuzumab can delay or prevent the progression to kidney failure.”
Next Steps and Ongoing Research
While the results from REGENCY are compelling, several important questions remain. Long-term follow-up will be essential to determine whether obinutuzumab confers sustained renal protection and reduces the incidence of ESRD or dialysis dependence. Additionally, further research is needed to understand how obinutuzumab compares with other emerging treatments for lupus nephritis, including voclosporin, belimumab, and novel pipeline agents.
Biomarker analyses from the REGENCY trial may also yield valuable insights into predictors of response and disease pathogenesis, potentially guiding personalized therapy for lupus patients. Future trials may evaluate the role of obinutuzumab in earlier stages of lupus nephritis or in combination with biologics targeting complementary immune pathways.
The publication of the REGENCY trial in The New England Journal of Medicine marks a pivotal milestone in the ongoing effort to improve outcomes for patients with lupus nephritis. By demonstrating that obinutuzumab can significantly enhance renal response rates when added to conventional therapy, the study lays the groundwork for broader adoption of this agent in clinical practice. As more data become available and long-term impacts are clarified, obinutuzumab could become a cornerstone in the management of this complex and challenging autoimmune condition.
For the millions affected by lupus around the world, these findings offer renewed hope—and a path forward toward more effective, targeted, and durable treatments.
