Abstract: SA-OR085
Efficacy and Safety of MIL62, a Glycoengineered Type II Anti-CD20 Antibody, in Primary Membranous Nephropathy: A Phase 3, Randomized, Controlled Trial
Session Information
- High-Impact Clinical Trials - 2
November 08, 2025 | Location: Hall A, Convention Center
Abstract Time: 11:15 AM - 11:30 AM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Cui, Zhao, Peking University First Hospital Department of Nephrology, Beijing, China
- Wei, Min, Beijing Mabworks Biotech Co Ltd, Beijing, China
- Li, Peng, Yantai Yuhuangding Hospital, Yantai, Shandong, China
- Wang, Rong, Shandong Provincial Hospital, Jinan, Shandong, China
- Li, Heng, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhang, Haitao, General Hospital of Eastern Theatre Command, Nanjing, Jiangsu, China
- Lin, Hong Li, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- Lan, Chen Xiao, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
- Luo, Ping, The Second Hospital of Jilin University, Changchun, Jilin, China
- Zhou, Hua, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- Xing, Guangqun, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- Li, Guisen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
- Li, Yuehong, Beijing Tsinghua Changgung Hospital, Beijing, China
- Chen, Wei, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
- Zhang, Junjun, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Yu, Chen, Tongji Hospital Affiliated to Tongji University, Shanghai, China
- Liang, Wei, Wuhan University Renmin Hospital, Wuhan, Hubei, China
- Yang, Qiongqiong, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Zheng, Hui Xiao, The Second Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei, China
- Li, Hua, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China
- Zhang, Yanning, People's Liberation Army Northern Theater Command, Shenyang, Liaoning, China
- Ni, Zhaohui, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
- Xu, Hui, Xiangya Hospital Central South University, Changsha, Hunan, China
- Chen, Xing, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- Zhao, Ming-Hui, Peking University First Hospital Department of Nephrology, Beijing, China
Group or Team Name
- Additional Contributing Research Centers and Sponsor: Members of the MIL62-CT307 Study Group: Xuzhou Medical University Affiliated Hospital; Zhujiang Hospital, Southern Medical University; The Second Xiangya Hospital of Central South University; Peking University People’s Hospital; The First Affiliated Hospital of Xi’an Jiaotong University; Yueyang People’s Hospital; Tongren Hospital, Shanghai Jiao Tong University School of Medicine; Beijing Mabworks Biotech Co., Ltd. (Sponsor).
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). Immunologic remission occurred in 87.5% vs 10.5% (P<0.0001), with a shorter time to immunologic remission for MIL62 (median, 1.1 vs. 3.0 months; P<0.0001). MIL62 reduced the risks of treatment failure (HR 0.04; 95%CI 0.01–0.11; P<0.0001) and relapse (HR 0.07; 95%CI 0.03–0.21; P<0.0001). Improvements in eGFR and EQ-5D were greater with MIL62. Safety profiles were broadly comparable; MIL62 was well tolerated with no new safety signals.
Conclusion
MIL62 significantly improved remission rates, accelerated disease control, and preserved kidney function versus cyclosporine, with acceptable safety. These results support MIL62 as a promising therapeutic option for Primary MN.