Genentech, a member of the Roche Group, announced positive topline results from the Phase III REGENCY study of Gazyva (obinutuzumab) in patients with active lupus nephritis. The study demonstrated that a higher proportion of patients treated with Gazyva plus standard therapy achieved a complete renal response (CRR) at 76 weeks compared to those treated with standard therapy alone.
The REGENCY study, a randomized, double-blind, placebo-controlled, multicenter trial, enrolled 271 patients with active lupus nephritis. Participants received either biannual intravenous doses of Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) or placebo plus standard therapy. The primary endpoint was the proportion of patients achieving CRR at 76 weeks.
Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Roche, stated, "Gazyva 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."
Key Findings from the REGENCY Study
The REGENCY study met its primary endpoint, demonstrating statistically significant and clinically meaningful treatment benefits in people with active lupus nephritis. Two key secondary endpoints also showed statistically significant and clinically meaningful benefits with Gazyva: the proportion of patients achieving CRR with a successful reduction of corticosteroid use, and an improvement in proteinuric response, both measured at 76 weeks. These endpoints are important indicators for achieving better disease control in lupus nephritis. Other secondary endpoints were not statistically significant, but numerically greater responses were observed for Gazyva in several endpoints.
Gazyva's Mechanism of Action
Gazyva (obinutuzumab) is a Type II engineered humanized monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. Gazyva depletes these disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease.
Lupus Nephritis: A Significant Unmet Need
Lupus nephritis is a potentially life-threatening manifestation of systemic lupus erythematosus, an autoimmune disease that commonly affects the kidneys. It affects approximately 1.7 million people worldwide, predominantly women, mostly women of color, and usually of childbearing age. Despite current treatment options, up to a third of people with lupus nephritis will develop end-stage kidney disease within 10 years, where dialysis or transplant are the only available options and the risk of mortality is high.
Regulatory and Clinical Development
Gazyva was granted Breakthrough Therapy Designation by the FDA in 2019, based on data from the Phase II NOBILITY study. Data from the REGENCY study are being shared with health authorities, including the FDA and the European Medicines Agency, with the goal of making this potential new treatment option for lupus nephritis available as soon as possible. Data are also being submitted for publication in a medical journal and presentation at a future medical congress.
In addition to REGENCY, Gazyva is being investigated in children and adolescents with lupus nephritis, people with membranous nephropathy, childhood-onset idiopathic nephrotic syndrome, and systemic lupus erythematosus (SLE).
