Anti-CD20 Antibody MIL62 Shows Promising Results in Phase 3 Study of NMOSD

Findings from a phase 3, randomized, double-blind, placebo-controlled trial (NCT05314010) showed that treatment with MIL62 (Mabworks Biotech), a glycoengineered type II anti-CD20 monoclonal antibody, led to low relapse risk and reduced disability progression in aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (NMOSD).¹

Over a 52-week treatment period, 4.4% of patients (2 of 25) randomized to MIL62 experienced a relapse compared with 45.7% (21 of 46) of those on placebo (HR, 0.069; 95% CI, 0.016-0.296; P <.001). In addition, investigators recorded an annualized relapse rate (ARR) of 0.092 in the MIL62 group vs 1.180 in the placebo cohort (rate ratio, 0.078; 95% CI, 0.018-0.333; P = .0006).

These data were presented as a late-breaker at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain. Led by Feng Li, chief executive officer at Mabworks, 91 AQP4-seropositive patients with NMOSD were assigned 1:1 to either MIL62 at 1000 mg intravenous doses at weeks 1, 3, 25, and 27, or placebo, for a 52-week period. Patients were stratified based on baseline Expanded Disability Status Scale (EDSS) scores, while time to first adjundicated relapse was the primary end point.

Coming into the study, the median ages of those in the MIL62 and placebo groups were 45.0 and 51.5 years, respectively, with those in the MIL62 group having slightly longer mean NMOSD disease duration (3.72 years vs 2.72). Within the 2 years prior to first treatment, the ARRs were 1.301 (MIL62) vs 1.359 (placebo), with mean baseline EDSS scores of 3.78 vs 3.41.

Additional efficacy data from the trial showed a reduction in annualized cumulative active MRI lesion rates with MIL62 (0.049 vs 1.412; rate ratio, 0.039; 95% CI, 0.005-0.2903; P = .0013), and improved disability (mean change in EDSS score from baseline to last visit: –0.39 vs +0.37; P = .019). Notably, MIL62-treated patients demonstrated statistically significant improvements in 4 exploratory end points, including Modified Rankin Scale, EQ-5D scale, as well as changes in pathogenic anti-AQP4 antibodies.

READ MORE: Tolebrutinib Preserves Notable MS Quality of Life Features in Non-Relapsing Secondary Progressive Multiple Sclerosis

The phase 3 study enrolled adults aged 18-60 with an EDSS score of 6.5 or lower, and a history of recent relapses requiring rescue therapy. Patients needed to have stable relapse symptoms for at least 12 weeks prior to the first dose. Key exclusions included recent use of B-cell depleting agents like rituximab (within 6 months), low CD20+ or CD4+ counts, or use of immunosuppressants such as mycophenolate, azathioprine, or tocilizumab within a defined window. Additionally, recent IVIG, plasmapheresis, or live vaccination within 28 days pre-treatment led to exclusion.

MIL62, which remains in development for other conditions like primary membranous nephropathy (PMN), systemic lupus erythematosus (SLE), and follicular lymphoma (FL), was considered to have a favorable safety profile. All told, there were more serious adverse events in the MIL62 group (11.1%) than those on placebo (6.5%), with no treatment-related deaths.

In 2024, a study published in The Lancet demonstrated the therapeutic potential of MIL62 in combination with lenalidomide, a cancer drug, to treat patients with relapsed FL or marginal zone lymphoma. The phase 1b/2a trial comprised 54 patients from 11 hospitals in China, testing the combination approach for 12 cycles, 28 days as a cycle. Spanning November 2019 to December 2020, the trial’s primary end point was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles.²

Among the 50 patients included in the efficacy analysis set, 43 (86%) achieved objective response, meeting the pre-specified primary end point. Disease control rate was 96% (48 of 50; 95% CI, 86-100), proportion of patients with a duration of response lasting at least 6 months was 77%. With a median follow-up of 12.3 months (IQR 12.0–12.6), the 1-year progression-free survival rate was 72% (95% CI: 57–83), the 9-month duration of response rate was 74% (95% CI: 58–85), and the 1-year overall survival rate was 98% (95% CI: 85–100).

Click here for more ACTRIMS 2025 coverage.

REFERENCES
1. Huang D, Wu L, Chen J, et al. Type II Anti-CD20 Antibody MIL62 in AQP4-Positive Neuromyelitis Optica Spectrum Disorder: A Multicenter, Randomized, Double-Blind, Phase III Trial. Presented at: 2025 ECTRIMS Congress; September 24-26; Barcelona, Spain. ABSTRACT 0132.
2. Shi Y, Zhou K, Zhou H, et al. Efficacy and safety of MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, combined with lenalidomide in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma: a multicentre, single-arm, phase 1b/2 trial. Lancet Neurol. 2024;73:102702. doi:10.1016/j.eclinm.2024.102702