Could obinutuzumab be the new therapy for adults with primary membranous nephropathy?

INTRODUCTION: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Anti-CD20 therapy is first-line when immunosuppression is indicated. However, a non-negligible proportion of patients fails to respond to rituximab, through mechanisms that include urinary drug loss and escape of tissue-resident B cells or long-lived plasma cells. Obinutuzumab, a glycoengineered humanized type II anti-CD20 antibody producing deeper, more sustained B-cell depletion, is a candidate to overcome these limitations. AREAS COVERED: We review the treatment landscape and unmet needs in primary MN; the chemistry, pharmacodynamics, pharmacokinetics and rationale of obinutuzumab; its clinical efficacy, including the MAJESTY trial; its safety profile; the competitive environment; and its regulatory status. PubMed was searched without date restrictions up to October 2026. EXPERT OPINION: Obinutuzumab is effective in primary MN, with the clearest indications being high anti-phospholipase A2 receptor (anti-PLA2R) titers, high-risk disease, severe rituximab hypersensitivity and rituximab-refractory disease. Key questions concern how best to use it: its pharmacokinetics in the nephrotic state are uncharacterized, and response-adapted dosing instead of the fixed four-dose regimen requires prospective validation. Persistent immunologic activity despite confirmed depletion argues for plasma cell-directed therapy. Standardized definitions of immunologic remission and resistance remain essential to generate better comparative evidence.