Primary membranous nephropathy is an antibody-driven kidney disease, and for years its drug regimens have been borrowed rather than designed for it. The Phase 3 MAJESTY trial, published June 5 in the New England Journal of Medicine, makes the case that a B-cell-depleting antibody built for lymphoma can clear more protein from the urine than the calcineurin inhibitor tacrolimus (Prograf). Important context up front: obinutuzumab (Gazyva) is FDA-approved only for chronic lymphocytic leukemia and follicular lymphoma. Its use in kidney disease is investigational and not approved, and this is a single trial — not a reason for any patient to change, stop, or request a switch in treatment.\n\n## Who was actually studied\n\nThe result applies to a narrow, hard-to-treat slice of patients, not to membranous nephropathy broadly. Per the trial registry (NCT04629248), enrollees had to have heavy, persistent proteinuria despite best supportive care — a urinary protein-to-creatinine ratio (UPCR) of at least 5 g/g after 3 months, or at least 4 g/g after 6 months — together with preserved kidney function (eGFR of at least 40 mL/min/1.73 m²). The trial excluded people with type 1 or type 2 diabetes and those with secondary membranous nephropathy, as well as anyone whose proteinuria had already fallen by half. In other words, these were adults whose disease had not responded to standard supportive care.\n\nIn the open-label trial, led by Fervenza et al. and funded by F. Hoffmann-La Roche/Genentech, investigators randomly assigned 142 such adults 1:1 to intravenous obinutuzumab or oral tacrolimus. The primary endpoint was complete remission at week 104 — a UPCR of 0.3 g/g or lower with a stable eGFR. At two years, complete remission was reached in 26 of 71 patients on obinutuzumab versus 4 of 70 on tacrolimus (37% vs. 6% after multiple imputation; adjusted difference 31 percentage points; 95% CI, 18 to 44; P<0.001).\n\n> The win is specific: complete remission of proteinuria at two years (37% vs. 6%). The trial did not establish a kidney-function benefit, and obinutuzumab is not approved for this disease.\n\n## What held and what didn’t\n\nThe trial used fixed-sequence hierarchical testing, which disciplines the secondary-endpoint claims. Complete-or-partial remission at week 104 and complete remission at week 76 — both key secondary endpoints — also showed a significant treatment effect. But the next endpoint in the hierarchy, a sustained eGFR reduction of at least 30%, did not reach significance, so by the trial’s own rules every endpoint below it was not formally tested. That shapes how to read the result: this is a strong proteinuria-remission finding, but not a demonstrated kidney-function-preservation finding. The drug did not beat tacrolimus at protecting how well the kidneys filter.\n\nSafety looked broadly comparable. Grade 3 or higher adverse events occurred in 16 obinutuzumab-treated patients (22%) versus 13 tacrolimus-treated patients (19%); serious adverse events occurred in 12 (17%) versus 10 (14%). Among obinutuzumab-treated patients, the drug’s reactions included infusion-related reactions, respiratory infections, and neutropenia. One patient in each group died during escape therapy.\n\nMAJESTY (NCT04629248) is active but not recruiting — enrollment is closed while the trial continues — with primary completion logged for December 2025 and full follow-up running to 2027, so the durability and eGFR questions are still open. The registry has not posted a results table; the figures here come from the peer-reviewed paper. Association is not causation, and this is reporting, not medical advice; treatment decisions belong with a patient and their nephrologist.