Neuromyelitis Optica Relapse Rate Plummets: Phase 3 Trial of Next-Generation Anti-CD20 Antibody Succeeds

Each relapse of neuromyelitis optica spectrum disorder can leave patients with vision or mobility impairments that are difficult to reverse. A phase 3 trial in China has now shown that the B-cell-targeting obinutuzumab β (MIL62, obinutuzumab β) can substantially reduce the risk of relapse, adding a treatment option supported by a randomized controlled study for this rare and severe autoimmune disease.

The double-blind, multicenter trial enrolled 91 patients aged 18 to 70 who had aquaporin-4 immunoglobulin G (AQP4-IgG) and randomly assigned them to receive intravenous obinutuzumab β or placebo. The primary endpoint was the first independently adjudicated relapse within 52 weeks: 2 of 45 patients in the treatment group relapsed, a proportion of 4.4%, compared with 21 of 46 patients in the placebo group, or 45.7%. The risk ratio was 0.069, equivalent to a 93.1% relative risk reduction, with an absolute difference of 41.3 percentage points between the groups in the proportion of patients who relapsed.

Other measures moved in the same direction. The annualized relapse rate was 0.092 in the treatment group and 1.180 in the placebo group; hospitalization due to relapse occurred in 4.4% and 45.7% of patients, respectively. The treatment group also had more favorable outcomes on disability scales and active magnetic resonance imaging lesions, although some analyses of disability worsening did not reach statistical significance, while vision remained broadly stable in both groups.

Obinutuzumab β is a glycoengineered type II anti-CD20 antibody that disrupts a key component of disease attacks by depleting B cells involved in the autoantibody response. It has the same amino acid sequence as obinutuzumab, but its Fc region is almost completely afucosylated, with the aim of enhancing antibody-dependent cellular cytotoxicity. In the trial, 86% of evaluable patients achieved peripheral B-cell depletion within 24 hours after the first dose.

The safety signals require a stratified interpretation. Grade 3 or higher adverse events judged to be treatment-related occurred in 6.7% of the treatment group and 6.5% of the placebo group; treatment-related events of all grades occurred in 66.7% and 45.7%, respectively, with infusion reactions, elevated liver enzymes, and decreased lymphocyte counts more common in the treatment group. One person in the treatment group died from multiple organ dysfunction. Investigators, while blinded, judged the death to be unrelated to the study drug, but the event nonetheless highlights that infection risk cannot be overlooked when critically ill patients receive B-cell depletion and high-dose corticosteroids.

As of May 2026, 90 people had received obinutuzumab β during the extension period. With a median follow-up of approximately 66 weeks, only 2 experienced a first relapse as determined by investigators, and no new relapses meeting the protocol definition were observed during the extension period; however, these data no longer had a randomized placebo comparator. More importantly, the overall median follow-up at the time of the primary analysis was only approximately 25 weeks. The study was also conducted solely in China, was limited to AQP4-IgG-positive patients, and did not directly compare the drug with other approved therapies. The study was supported by the developer, Beijing Mabworks Biotech, and the funder participated in its design, analysis, and manuscript preparation. The drug was approved in China for this disease in February 2026. Longer-term data encompassing more diverse populations are still needed to clarify the durability of efficacy and risks including rare infections and reduced immunoglobulin levels.