Obinutuzumab β for aquaporin-4-positive neuromyelitis optica spectrum disorder: a phase 3 randomized controlled trial

Although CD20-directed B cell depletion has long been used in neuromyelitis optica spectrum disorder (NMOSD), high-quality, large-scale, randomized controlled trials remain limited. In this multicenter, randomized, double-blind phase 3 trial, we evaluated obinutuzumab β (MIL62), a novel glycoengineered type II anti-CD20 monoclonal antibody, in patients with NMOSD. Eligible participants aged 18−70 years with aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive NMOSD and an Expanded Disability Status Scale (EDSS) score of 7.0 or lower were randomly assigned (1:1) to receive intravenous obinutuzumab β 1,000 mg (n = 45) or placebo (n = 46). The primary outcome—time to first adjudicated relapse on or before week 52—was met: relapse occurred in two of 45 (4.4%) obinutuzumab β-treated participants and in 21 of 46 (45.7%) placebo-treated participants (hazard ratio = 0.069, 95% confidence interval: 0.016−0.296, P < 0.0001). The incidence of grade 3 or higher treatment-related adverse events was similar between the obinutuzumab β group (6.7%) and the placebo group (6.5%). These findings support obinutuzumab β as a glycoengineered type II anti-CD20 therapeutic option for patients with AQP4-IgG+ NMOSD. ClinicalTrials.gov identifier: NCT05314010 . In a phase 3 trial, obinutuzumab β significantly reduced relapse risk by 93.1% versus placebo in patients with AQP4-IgG+ NMOSD, improved clinical and MRI outcomes, showed manageable safety and demonstrated sustained efficacy with no relapses during extended follow-up.