Type II Glycoengineered Anti-CD20 Antibody MIL62 or Cyclosporine in Chinese Primary Membranous Nephropathy: A Multicenter, Randomized, Open-Label Phase 1b/2 Trial

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Background: A novel glycoengineered type II anti-CD20 antibody, MIL62 with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Last year, we we announced that the 12-week immunological remission rate and 24-week overall remmision rate (ORR) of MIL62 was significantly higher than CsA, meeting the primary endpiont of this study. Here we will update the follow-up data for week 76. Methods: Eligible patients with pMN diagnosed by kidney biopsy, proteinuria of at least 3.5 g per 24 hours received intravenous MIL62 (two infusions, 600 or 1000 mg each, administered 14 days apart; repeated at 6 months) or Cyclosporine (CsA, starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed up for up to 104 weeks after initial administration. The primary efficacy outcome was a composite of complete or partial remission of proteinuria and stable eGFR. Safety and anti-PLA2R antibodies were also assessed. Results: From Feb. 23th, 2022 to Jan. 13th, 2023, a total of 87 patients were randomly enrolled from 19 centers in China. One patient in the MIL62 group discontinued the intervention. As of Apr. 22th, 2024, all the 86 patients had evaluable data at 52 weeks and 75 patients had data at 76 weeks. The complete remission rates (CRR) of MIL62 group and cyclosporine group were 20/60 (33.3%) and 1/26 (3.8%) at 52 weeks (risk difference, 29.5%; 95% CI, 15.5 to 43.5; P=0.003 for superiority), and 23/49 (46.9%) and 0/26 (0.0%) (P<0.001) at 76 weeks. The ORR of MIL62 group and cyclosporine group were 48/60 (80.0%) and 3/26 (11.5%) at 52 weeks (risk difference, 68.5%; 95% CI, 52.5 to 84.4; P<0.001 for superiority), and 35/49 (71.4%) and 2/26 (7.7%) (P<0.001) at 76 weeks.Treatment-related adverse events occurred in 76.7%, 80.6% and 88.5% of MIL62 600mg, MIL62 1000mg and cyclosporine group respectively. No treatment-related death occurred. Conclusion: MIL62 was superior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months. A phase 3 clinical trial of MIL62 in pMN is ongoing (NCT05862233).

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