Efficacy and Safety of MIL62, a Glycoengineered Type II Anti-CD20 Antibody, in Primary Membranous Nephropathy: A Phase 3, Randomized, Controlled Trial

作者：Zhao Cui, Min Wei, Peng Li, Rong Wang, Heng Li, Haitao Zhang, Hong Lin, Chen Xiao Lan, Ping Luo, Hua Zhou, Guangqun Xing, Guisen Li, Yuehong Li, Wei Chen, Junjun Zhang, Yu Chen, Wei Liang, Qiongqiong Yang, Hui Zheng, Hua Li, Yanning Zhang, Zhaohui Ni, Xu Hui, Xing Chen, Ming Zhao · 发表于：Journal of the American Society of Nephrology · 年份：2025 · DOI：10.1681/asn.202564sha3em · 被引用次数：3 · 研究领域：Renal Diseases and Glomerulopathies、Vasculitis and related conditions、Renal and Vascular Pathologies

Background: Primary membranous nephropathy (MN) is driven by autoreactive B cells producing antibodies to podocyte antigens (e.g., PLA2R), leading to nephrotic-range proteinuria and progressive kidney injury. MIL62 is a glycoengineered, type II anti-CD20 monoclonal antibody designed to enhance antibody-dependent cellular cytotoxicity and deepen B-cell depletion. Methods: In this multicenter, randomized, open-label, phase 3 trial (NCT05862233), adults with biopsy-proven MN were assigned 1:1 to MIL62 (1000 mg intravenously at Weeks 1, 3, 25, 27, and 53) or cyclosporine (CsA, trough 125–175 ng/mL for 52 weeks, then tapered up to 8 weeks). Follow-up continued to Week 104. The primary endpoint was complete remission (CR) at Week 76, defined as urine protein-creatinine ratio (UPCR) <0.3 g/g with <15% eGFR decline. Secondary endpoints included CR at Week 52, overall remission, times to immunologic/clinical remission, relapse and treatment failure, renal function, quality of life (EQ-5D), and safety. Results: A total of 153 patients received treatment (MIL62 n=77; CsA n=76). MIL62 achieved a higher CR rate at Week 76 than CsA (49.4% vs. 3.9%, difference 46.5%, 95%CI 32.1–60.9, P<0.0001; RR 12.5, 95%CI 4.0–39.0). CR at Week 52 also favored MIL62 (37.7% vs. 6.6%, P<0.0001). Overall remission rates were superior with MIL62 at Weeks 24, 52, and 76 (all P<0.001). Median time to CR was 14.1 months (95%CI 10.4-17.7) with MIL62 and was not reached with CsA (HR 4.3; 95%CI 2.4–7.8; P<0.0001). ...