Novel anti-CD20 antibody shows efficacy in AQP4-IgG-positive NMOSD

In a phase 3 trial, the novel glycoengineered type II anti-CD20 monoclonal antibody MIL62 significantly reduced the risk of relapse and disability progression in aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), with a favourable safety profile.

In this double-blind, placebo-controlled trial (NCT05314010), 91 AQP4-IgG-seropositive NMOSD patients were randomised 1:1 to placebo or MIL62 (1,000 mg IV at weeks 1, 3, 25, and 27) [1]. The primary endpoint was time to first adjudicated relapse (TFR). Prof. De-hui Huang (Chinese PLA General Hospital, China) presented the results. The median age in the MIL62 and placebo groups was 45.0 and 51.5 years, respectively; 95.6% and 87.0% of the participants were female. Mean disease duration was 3.73 and 2.72 years, and mean baseline Expanded Disability Status Scale (EDSS) scores were 3.78 and 3.41. All but 1 participant had received corticosteroids; approximately 1/3 were also on immunosuppressive therapy.

In the complete analysis set, median follow-up was 26.3 weeks in the MIL62 group, compared to 22.1 weeks for placebo. Over 52 weeks, 23 first relapses occurred: 2 (4.4%) in the MIL62 group compared to 21 (45.7%) in the placebo group (HR, 0.069; 95% CI, 0.016-0.296; P<0.0003). The annualised relapse rate (ARR) was 0.092 with MIL62 versus 1.180 with placebo (rate ratio 0.078; 95% CI 0.018-0.333; P=0.0006). This equates to a 93.1% reduction in relapse risk. Additional findings showed lower cumulative rates of active MRI lesions and an improvement in disability.

Treatment-related adverse events (TRAEs) in ≥5% of participants were more frequent with MIL62, but all were grade 1-2 and resolved with supportive care. The most common TRAEs were infusion-related reactions (22.2%), elevated alanine aminotransferase (13.3%), elevated blood lactate dehydrogenase (11.1%), and decreased lymphocyte count (11.1%). No treatment discontinuations or deaths occurred. An open-label extension is ongoing.

1. Huang D, et al. Type II Anti-CD20 antibody MIL62 in aquaporin-4–positive neuromyelitis optica spectrum disorder: a multicenter, randomized, double-blind, phase III trial. O132, ECTRIMS 2025 Congress, 24-26 September 2025, Barcelona, Spain.

Medical writing support was provided by Michiel Tent.

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Posted on 30 September 2025