Phase 3 MAJESTY Trial Shows Obinutuzumab Achieves Superior Complete Remission Over Tacrolimus in Primary Membranous Nephropathy
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Phase 3 results announced in February 2026 show that obinutuzumab, an anti-CD20 monoclonal antibody, achieved significantly higher rates of complete kidney remission at two years compared to the immunosuppressant tacrolimus in patients with primary membranous nephropathy. The MAJESTY trial enrolled 142 patients and met its primary endpoint as well as all key secondary endpoints, including earlier complete remission and higher overall remission rates. If approved, obinutuzumab would be the first therapy specifically indicated for primary membranous nephropathy, where patients currently face limited treatment options and substantial risk of progression to end-stage kidney disease.
Abstract
Primary membranous nephropathy (PMN) is an autoimmune kidney disease in which antibodies, most commonly targeting the phospholipase A2 receptor (PLA2R), trigger immune complex deposition along the glomerular basement membrane, causing progressive proteinuria and kidney injury. Approximately 30 to 40% of patients with severe proteinuria progress to end-stage renal disease or significant irreversible kidney failure within 10 years. No therapy has been specifically approved for PMN, and management has relied on immunosuppressive regimens including calcineurin inhibitors such as tacrolimus, cyclophosphamide, and off-label use of B-cell depletion with rituximab.
Obinutuzumab is a humanized, glycoengineered type II anti-CD20 monoclonal antibody that produces more robust B-cell depletion than first-generation anti-CD20 agents through enhanced antibody-dependent cellular cytotoxicity and direct cell-death activity. MAJESTY was a phase 3, randomized, open-label, multicenter study evaluating obinutuzumab compared to tacrolimus in 142 adults with PMN. Participants were randomized 1:1, and the primary endpoint was the percentage of patients achieving complete remission at week 104 (two years).
The trial met its primary endpoint, with a statistically significantly greater proportion of patients in the obinutuzumab group achieving complete remission at two years compared to those treated with tacrolimus. Key secondary endpoints also demonstrated statistically significant and clinically meaningful advantages for obinutuzumab, including higher rates of overall remission (complete or partial) at week 104 and improved complete remission rates at week 76. Safety was consistent with the established profile of obinutuzumab, with no new safety signals identified. These results suggest obinutuzumab may offer a more effective, disease-modifying approach for primary membranous nephropathy than current immunosuppressive standards of care, and Genentech has indicated plans to pursue regulatory approval.