Efficacy and safety of ripertamab in immune-mediated glomerular diseases with proteinuria: an expanded real-world cohort study.

Background: Ripertamab (SCT400), a recombinant anti-CD20 monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity, has shown efficacy in primary membranous nephropathy (PMN). This study evaluated its broader therapeutic potential in immune-mediated glomerular diseases with proteinuria. Methods: In this ambispective real-world cohort study, 176 adult patients with biopsy-confirmed immune-mediated glomerular diseases presenting with proteinuria were enrolled, comprising 52 patients from a prior PMN analysis and 124 newly enrolled patients with diverse pathologies. Patients were stratified into initial therapy (n = 131) and alternative therapy (n = 45, prior treatment failure or relapse) groups. The PMN cohort (n = 150) was designated as the primary efficacy population; the primary efficacy outcomes were the proportions of patients achieving complete remission (CR) or partial remission (PR) at 3, 6, 9, and 12 months in the PMN cohort. Outcomes of non-PMN patients (n = 26) were prespecified as exploratory and descriptive only. Results: The median potential follow-up was 19.5 (9.3, 28.5) months, and the median observed clinical follow-up was 9.3 (4.7, 18.1) months. In the PMN cohort, among patients with evaluable data at each respective timepoint, the CR/PR proportions were 45.6% (41/90) at 3 months, 54.4% (37/68) at 6 months, 59.6% (34/57) at 9 months, and 66.7% (30/45) at 12 months, with a 12-month CR rate of 15.6% (7/45). Previously treated patients achieved remission significantly more slowly than treatment-naive patients (median 232.5 vs. 83.0 days, P = 0.040), whereas complete-remission time did not differ; 12-month estimates were limited by small subgroups. Of the 77 PMN patients who achieved remission and had subsequent follow-up, 25 (32.5%) relapsed. Safety was favorable: AE incidence was 9.1%, with no Grade ≥3 AEs or treatment-related deaths. Conclusions: In this single-arm, observational PMN cohort, ripertamab monotherapy was associated with clinically meaningful remission and favorable tolerability; causality cannot be established without a concurrent control group. Among evaluable patients, 12-month CR/PR was 69.4% and 55.6% in treatment-naïve and previously treated patients, respectively; the latter was based on only nine patients, who also remitted more slowly. These hypothesis-generating findings warrant controlled evaluation of ripertamab in PMN, including refractory disease. Non-PMN evidence remains exploratory.