Daratumumab Demonstrates 76% Reduction in Relapse Risk for NMOSD in Phase 3 DAWN Trial
核心洞察
The phase 3 DAWN trial showed daratumumab, an anti-CD38 (搜索) monoclonal antibody, reduced relapse risk by 76% compared to placebo in patients with aquaporin-4 (搜索) antibody-positive neuromyelitis optica spectrum disorder (搜索).
The study enrolled 135 patients across eight centers in China, with daratumumab demonstrating efficacy within the range of currently approved NMOSD (搜索) treatments and showing potential neurological function improvement.
Daratumumab targets CD38 (搜索)-positive plasmablasts, plasma cells, and natural killer cells, offering a more selective approach to reducing pathogenic antibody production compared to broad B-cell depletion therapies.
The investigational anti-CD38 (搜索) monoclonal antibody daratumumab achieved a 76% reduction in relapse risk compared to placebo in patients with neuromyelitis optica spectrum disorder (搜索) (NMOSD (搜索)), according to late-breaking data from the phase 3 DAWN trial presented at the 2026 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum in San Diego, California.
The double-blind, randomized, placebo-controlled trial enrolled 135 patients with aquaporin-4 (搜索) antibody-positive NMOSD (搜索) across eight centers in China. Participants received either intravenous daratumumab (n=90) at 8 mg/kg for 2 weeks followed by 4 mg/kg every 4 weeks, or placebo (n=45). The primary endpoint of time to first relapse showed a hazard ratio of 0.26, placing daratumumab's efficacy within the range of other approved NMOSD treatments.
Targeting Multiple Immune Pathways
Daratumumab, currently approved for multiple myeloma (搜索), targets CD38 (搜索)-positive plasmablasts and plasma cells—the primary producers of pathogenic aquaporin-4 (搜索) antibodies in NMOSD (搜索). The therapy also depletes CD38-expressing natural killer cells, potentially reducing antibody-dependent cytotoxic injury to astrocytes.
"CD38 (搜索) is not only expressed on antibody generating cells but also on natural killer cells, which participate in antibody dependent cytotoxicity," explained Fu-Dong Shi, MD, PhD, professor of neurology at Beijing Tiantan Hospital (搜索) and study co-author. "By targeting both of these populations, this approach may reduce antibody production while also limiting immune mediated damage to astrocytes, which is central to the disease process in NMOSD (搜索)."
Functional Improvement Beyond Relapse Prevention
Unlike previous NMOSD (搜索) trials that primarily focused on relapse prevention, the DAWN trial demonstrated measurable improvement in neurological function as assessed by the Expanded Disability Status Scale (EDSS). Michael Levy, MD, PhD, associate professor of neurology at Massachusetts General Hospital and study co-author, noted this represents a significant advancement.
"It is important to note that we did not just see stabilization. Many patients actually showed improvement in neurological function compared with placebo, where relapses drove worsening," Levy told NeurologyLive®. "In other pivotal NMOSD (搜索) trials, we have focused primarily on relapse prevention, so seeing measurable improvement in EDSS adds a very compelling layer to the clinical impact of this therapy."
Patient Population and Safety Profile
The trial enrolled adults aged 18 years or older with confirmed NMOSD (搜索) who were seropositive for anti-aquaporin-4 (搜索) antibodies and had active disease, defined by at least one relapse in the prior 12 months or two relapses in the past 24 months. Disability levels were capped at an EDSS score of 7.5 or lower.
Key exclusions included recent use of high-dose intravenous steroids, IVIG, or plasma exchange within three weeks, as well as recent exposure to biologics or oral immunosuppressants. Patients previously treated with rituximab or inebilizumab within six months were excluded.
The treatment demonstrated a favorable safety profile, with mostly minor injection-related reactions as adverse events. No major safety signals were identified in the phase 3 findings, consistent with daratumumab's established safety profile in multiple myeloma (搜索).
Addressing Unmet Medical Needs
The results address several unmet needs in NMOSD (搜索) treatment, including options for patients who fail current therapies or develop long-term complications from existing treatments. Current approved NMOSD therapies require lifelong treatment and can lead to complications such as hypogammaglobulinemia and infections with prolonged B-cell depletion.
"You cannot deplete B cells indefinitely without consequences," Levy explained. "Over time, patients may develop hypogammaglobulinemia, infections, and other complications. In addition, there are patients who fail B-cell–directed therapies, whether that is an approved agent or off-label rituximab."
The study represents the first large trial of daratumumab in an organ-specific neurologic autoimmune condition, building on smaller studies in systemic lupus erythematosus (搜索) and other autoimmune diseases. The investigators noted that daratumumab is less expensive than some currently approved NMOSD (搜索) therapies and could potentially benefit more patients if results are validated and partnerships established.
Currently, no other ongoing trials are examining daratumumab in NMOSD (搜索), though the study authors expressed optimism about the drug's potential in this patient population and the broader goal of developing therapies that patients may eventually discontinue.