The Type II Glycoengineered Anti-CD20 Antibody MIL62 or Cyclosporine in Chinese Primary Membranous Nephropathy: Updated Results of an Ongoing, 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. We have many clinical data of MIL62 in lymphoma, so we chose two doses to evaluate the safety, tolerability, and efficacy of MIL62 in pMN. Methods: Eligible pts 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. The primary outcome were immunological remission (iR) at 12 weeks and a composite of complete or partial remission of proteinuria with stable eGFR at 24 weeks. Results: From Feb. 23th, 2022 to Dec. 21th, 2022, 86 patients (pts) were randomly enrolled. As of Mar. 23th, 2023, median follow up time was 24 weeks. 22/35 (62.9%) pts in the MIL62 group and 6/18 (33.3%) pts in the CsA group achieved remission at 24 weeks (P< 0.05). In the 69 pts positive for anti-PLA2R Abs (≥14RU/mL) at baseline, 41/47 (87.2%) pts in the MIL62 group achieved iR, which was superior to the CsA group [12/22 (54.5%), P< 0.05] at 12 weeks. The remission to MIL62 in our study was faster than Rituximab because 62.9% (22/35) of patients achieved complete or partial remission at 24 weeks compared with the 35% (23/65) 6-month response rate reported in the Mentor study. Treatment-related adverse events occurred in 73.3%, 77.1% and 88.5% pts in the MIL62 600mg, MIL62 1000mg and CsA group respectively; No treatment-related deaths occurred. Conclusions: The 12-week iR and 24-week overall remmision of MIL62 was significantly higher than CsA, and had a manageable safety profile. A phase III clinical trial of MIL62 in pMN is ongoing (NCT05862233). - Immunological Remission at 12 weeks Overall Remission at 24 weeks MIL62 (N=47) Cyclosporine (N=22) MIL62 (N=35) Cyclosporine (N=18) Remission rate n (%), 95%CI 42 (87.2) (74.3, 95.2) 12 (54.5) (32.2, 75.6) 22 (62.9) (44.9, 78.5) 6 (33.3) (13.3, 59) p value p=0.003 p=0.041

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