MIL62 Shows Increased Remission and Reduced Relapse Versus Cyclosporine A in MN

New research shows MIL62 achieved significantly increased complete remission rates than cyclosporine A in adults with primary membranous nephropathy (MN).1

The 2-year, multicenter, randomized, open-label phase 3 trial evaluated whether adults with biopsy-proven MN achieved complete remission, defined as a urine protein-creatinine ratio (UPCR) <0.3 g/g with <15% decline in estimated glomerular filtration rate (eGFR) compared to standard-of-care cyclosporine A.1

Membranous nephropathy is characterized by nephrotic-range proteinuria (>3.5 g/day) caused by antibodies targeting native podocyte antigens, most commonly the phospholipase A2 receptor (PLA2R). Approximately 75%-80% of MN cases are primary autoimmune, while the remainder are secondary to other conditions.2

Cyclosporine A, a calcineurin inhibitor, is a standard treatment option for moderate-to-high risk MN. Cyclosporine A suppresses T-cell activity and stabilizes podocytes, thereby helping to control nephrotic syndrome and reduce proteinuria. The therapy does not eliminate PLA2R antibodies or B cells, leaving the underlying autoimmune process unchanged. As a result, relapse often occurs when treatment stops.1,2

MIL62 is a glycoengineered, type II anti-CD20 monoclonal antibody intended to enhance antibody-dependent cellular cytotoxicity and deepen B-cell depletion and directly address the autoimmune drivers of primary MN.1

In the phase 3 trial, 153 adults with biopsy-proven MN were randomly assigned in a 1:1 ratio to 1000 mg intravenous MIL62 (n = 77) at week 1, 3, 25, 27, and 52, or 52-week trough 125-175 ng/mL cyclosporine A (n = 76), tapered for up to 8 weeks. The primary endpoint was complete remission at week 76. Secondary endpoints included overall remission, times to immunologic/clinical remission, relapse and treatment failure, renal function, quality of life, safety, and complete remission at week 52.1

By week 76, complete remission occurred in 49.4% of patients receiving MIL62 compared with 3.9% receiving cyclosporine A, an absolute difference of 46.5% (95% confidence interval [CI], 32.1-60.9; P <.0001; RR, 12.5; 95% CI, 4.0-39.0). At week 52, complete remission rates continued to favor MIL62 over cyclosporine A (37.7% vs 6.6%; P <.0001). Overall remission rates were consistently higher with MIL62 at weeks 24, 52, and 76 (all P <.001).1

MIL62 also accelerated disease control with a median time to complete remission of 14.1 months (95% CI, 10.4 to 17.7) with MIL62, whereas the median time was not reached in the cyclosporine A group (Hazard Ratio [HR], 4.3; 95% CI, 2.4 to 7.8; P <.0001). Immunologic remission occurred in 87.5% of patients treated with MIL62 compared with 10.5% of those receiving cyclosporine A (P <.0001), with a shorter median time to immunologic remission (1.1 vs 3.0 months; P <.0001).1

Risks of treatment failure (HR, 0.04; 95% CI, 0.01 to 0.11; P <.0001) and relapse (HR, 0.07; 95% CI, 0.03 to 0.21; P <.0001) were decreased with MIL62 amd improvements in eGFR and quality of life were increased in the MIL62 patient population. Between both patient populations, safety profiles were broadly comparable, and MIL62 demonstrated no new safety signals.1

“MIL62 significantly improved remission rates, accelerated disease control, and preserved kidney function versus cyclosporine, with acceptable safety,” wrote Zhao Cui, MD, associate professor at Peking University, and colleagues. “These results support MIL62 as a promising therapeutic option for Primary MN.”1

References

1. Cui Z, Wei M, Li P, et al. Efficacy and Safety of MIL62, a Glycoengineered Type II Anti-CD20 Antibody, in Primary Membranous Nephropathy: A Phase 3, Randomized, Controlled Trial. October 2025 - Volume 36 - Issue 10S: Journal of the American Society of Nephrology. Published online October 2025. Accessed November 18, 2025. https://journals.lww.com/jasn/fulltext/2025/10001/efficacy_and_safety_of_mil62

2. Alok A, Yadav A. Membranous Nephropathy. StatPearls. Published June 5, 2023. Accessed November 18, 2025 https://www.ncbi.nlm.nih.gov/books/NBK559169/