Daratumumab is a promising novel treatment for NMOSD

Daratumumab, a humanised monoclonal antibody targeting the CD38 glicoprotein, reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD) in the phase 3 DAWN-trial.

“You may ask yourself: neuromyelitis optica, did we not already solve that problem?” asked Prof. Michael Levy (Massachusetts General Hospital, MA, USA) [1]. New therapies with novel mechanisms of action are therefore needed to address these failure rates and safety concerns associated with long-term B-cell depletion.

Daratumumab is a first-in-class humanised monoclonal antibody targeting CD38, representing a novel therapeutic approach in NMOSD. The DAWN study (NCT05403138) was a prospective, double-blind, randomised, parallel-group, phase 3 trial evaluating the safety and efficacy of daratumumab in patients with AQP4-IgG-positive NMOSD. The 135 enrolled participants had experienced at least 1 relapse in the past year or at least 2 relapses in the past 2 years. They were randomised 2:1 to daratumumab (n=90) or placebo (n=45), administered intravenously at 8 mg/kg for 2 weeks, followed by 4 mg/kg doses every 4 weeks thereafter. The primary endpoint was time to first relapse after 48 weeks.

The relapse risk was 74% lower in the daratumumab group than in the control group (HR 0.26; 95% CI 0.14–0.48), which Prof. Levy noted fell within the efficacy range of other approved NMOSD treatments. The on-trial annualised relapse rate (ARR) decreased from 1.0 at baseline to 0.13 in the

daratumumab group, and from 0.9 to 0.51 in the placebo group. EDSS worsening occurred in 5 patients (6%) in the daratumumab group versus 16 (36%) in the placebo group. Notably, some patients in the daratumumab group who did not relapse showed improved neurological function rather than remaining stable.

Daratumumab was well tolerated, with no unexpected safety signals. Hypogammaglobulinaemia was observed, but without a significant increase in infection rates. The authors concluded that the enhanced selectivity for antibody-generating plasmablasts and plasma cells, rather than pan-B lymphocytes, may prove safer and more suitable for long-term maintenance therapy in NMOSD.

Zhang C, et al. Anti-CD38 mAb daratumumab in neuromyelitis optica spectrum disorders (DAWN): A multicenter, randomized, double-blind, placebo-controlled phase III trial. LB1.2, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.