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

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.