Gazyva/Gazyvaro Shows Improved Complete Renal Response Among Patients with Lupus Nephritis

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Findings from the Phase III REGENCY trial (NCT04221477) demonstrated that Gazyva/Gazyvaro (obinutuzumab; Roche) in combination with standard therapy of mycophenolate mofetil and glucocorticoids achieved the primary endpoint of a higher rate of complete renal response (CRR) in patients with lupus nephritis compared to standard therapy alone.^1,2

The CD20-directed cytolytic antibody 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.

“I am very excited about today’s announcement that the Phase III REGENCY study has met its primary endpoint,” REGENCY trial investigator Brad H. Rovin, MD, director of Nephrology and medical director of the Center for Clinical Research Management at The Ohio State University Wexner Medical Center, said in a press release. “The results of REGENCY are compelling. Obinutuzumab could offer the lupus community an effective new treatment option for controlling this difficult disease that can be associated with high morbidity for individuals living with lupus.”¹

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.

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. Investigators noted that the trial’s patient population is representative of the real-world population of patients with the disease.

Investigators randomly assigned 271 patients in a 1:1 ratio to receive biannual intravenous dosing of Gazyva/Gazyvaro with standard therapy to compare with placebo plus standard therapy. 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.

In addition to achieving the trial’s primary endpoint, investigators also observed statistically significant and clinically meaningful results for the endpoint of proportion of patients experiencing CRR while successfully reducing corticosteroid use at 76 weeks, as well as improved proteinuric response at 76 weeks. The trial’s other secondary endpoints were not found to be statistically significant but were numerically in favor of Gazyva/Gazyvaro, including mean change in estimated glomerular filtration rate at 76 weeks, death or renal-related events through 76 weeks, and overall renal response at 50 weeks.

Roche stated that it will share full data from the trial with health authorities, as well submitting the data for publication in a medical journal and presenting it at a future medical congress.

“Gazyva/Gazyvaro achieved a robust complete renal response rate in lupus nephritis, which is associated with long-term preservation of kidney function and delay or prevention of end-stage kidney disease,” Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development. “Since dialysis or transplants are often required for patients with advanced kidney disease, these findings could represent an important step forward for people living with this devastating disease.”¹

References

1. Positive phase III results for Roche’s Gazyva/Gazyvaro show superiority to standard therapy alone in people with lupus nephritis. News release. Roche. September 26, 2024. Accessed September 27, 2024. https://www.roche.com/media/releases/med-cor-2024-09-26 https://www.roche.com/media/releases/med-cor-2024-09-26

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 July 17, 2024. Accessed September 27, 2024. https://clinicaltrials.gov/study/NCT04221477