Phase III REGENCY Trial Confirms Gazyva/Gazyvaro Significantly Improves Kidney Outcomes in Lupus Nephritis Patients

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Updated results from the Phase III REGENCY trial (NCT04221477) show that patients with lupus nephritis administered Gazyva/Gazyvaro (obinutuzumab) plus standard therapy achieved a statistically significant and clinically meaningful improvement in complete renal response (CRR) compared to standard therapy alone.^1,2 The trial data, also published by The New England Journal of Medicine, bolster prior findings suggesting deep B-cell depletion with Gazyva/Gazyvaro is an effective therapeutic option for patients with lupus nephritis.³

“The fact that nearly half of lupus nephritis patients achieved a complete renal response, together with clinically meaningful benefits observed consistently across subgroups, indicates superior disease control with Gazyva/Gazyvaro compared to standard treatment alone,” said Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development. “Lupus nephritis disproportionately affects younger women, mostly women of color, often leading to end-stage kidney disease. Our goal is to address this urgent need by providing a more effective treatment option.”

Gazyva/Gazyvaro is a CD20-directed cytolytic antibody that is currently approved in more than 100 countries for the treatment of lymphoma, including in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia; in combination with chemotherapy followed by Gazyva monotherapy in patients with stage II bulky, III, or IV follicular lymphoma (FL); and combined with (Bendeka) bendamustine followed by Gazyva monotherapy for FL in adults who did not respond to a rituximab-containing regimen, or whose FL returned.

Up to one-third of patients with lupus nephritis go on to develop end-stage kidney disease within 10 years, for which dialysis or transplant are the only available therapeutic options and carry a high risk of mortality. Investigators have found that Gazyva/Gazyvaro reduces the disease-causing B cells that cause inflammation in these patients, which may limit kidney damage and could prevent or delay patients from progressing to end-stage kidney disease.

Trial Design

The randomized, double-blind, placebo-controlled, multicenter REGENCY trial evaluated the efficacy and safety of Gazyva/Gazyvaro combined with standard therapy in patients with active and chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V.

The trial’s primary endpoint was CRR at week 76, defined as urinary protein-to-creatinine ratio of less than 0.5, estimated glomerular filtration rate of at least 85% of baseline value, and no intercurrent. Key secondary endpoints at week 76 included CRR with a prednisone dose of 7.5 mg per day or lower between weeks 64 and 76, and urinary protein-to-creatinine ratio lower than 0.8 without an intercurrent event.

Investigators randomly assigned 271 patients in a 1:1 ratio to receive biannual intravenous dosing of Gazyva/Gazyvaro with standard therapy (n = 135) to compare with placebo plus standard therapy (n = 136). The trial’s primary endpoint was the proportion of patients able to achieve CRR at 76 weeks, with key secondary endpoints that included proportion of patients achieving CRR at week 76 with successful decrease of corticosteroid use; proportion of those achieving proteinuric response at 76 weeks; mean change in estimated glomerular filtration rate after 76 weeks; death or renal-related events through 76 weeks; and overall renal response at 50 weeks.

At 76 weeks, CRR was achieved by 46.4% of patients in the Gazyva/Gazyvaro cohort compared to 33.1% of patients in the placebo cohort (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 2.0 to 24.8; P=0.02). Additionally, CRR with a daily 7.5 mg or lower dose of prednisone between weeks 64 and 76 was achieved by 42.7% of patients in the Gazyva/Gazyvaro cohort compared to 30.9% of patients in the placebo cohort (adjusted difference, 11.9 percentage points; 95% CI, 0.6 to 23.2; P=0.04).

Further, 55.5% of patients in the Gazyva/Gazyvaro cohort achieved a urinary protein-to-creatinine ratio lower than 0.8 without an intercurrent event compared to 41.9% of patients in the placebo cohort (adjusted difference, 13.7 percentage points; 95% CI, 2.0 to 25.4; P=0.02).

In terms of safety, there were no unexpected signals reported. There were more serious adverse events reported in the Gazyva/Gazyvaro cohort, which were primarily infections and events related to COVID-19.

“The positive REGENCY study results confirmed the findings of an earlier trial that administration of obinutuzumab, a therapy which targets B cells, benefitted patients with lupus nephritis more than standard treatment alone,” Richard Furie, MD, Marilyn and Barry Rubenstein Chair in Rheumatology and chief of the Division of Rheumatology at Northwell Health, US, said in the release. “It is also gratifying to see that patients who received obinutuzumab were not only more likely to achieve the desired outcome but were able to taper corticosteroids at the same time.”1

References

1. New England Journal of Medicine publishes new data for Roche’s Gazyva/Gazyvaro which shows superiority over standard therapy in people with active lupus nephritis. News release. Roche. February 6, 2025. Accessed February 7, 2025. https://www.roche.com/media/releases/med-cor-2025-02-07

2. A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/​RPS 2003 Class III Or IV Lupus Nephritis (REGENCY). ClinicalTrials.gov. Updated January 14, 2025. Accessed February 7, 2025. https://clinicaltrials.gov/study/NCT04221477

3. Furie R. et al. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med 2025; doi/full/10.1056/NEJMoa2410965.