Divozilimab Cuts Relapse Risk at 1 Year in Phase 3 AQUARELLE Trial of NMOSD

One-year data from the phase 3 AQUARELLE study show that divozilimab (Biocad), an anti-CD20 monoclonal antibody, reduced relapse activity in patients with neuromyelitis optica spectrum disorder (NMOSD). Investigators presented the findings at the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026), held October 21-23 in Toronto, Canada.¹

The analysis was led by Alexey Boyko, professor at Pirogov National Medical Research University's Federal Center for Brain Research and Neurotechnologies in Moscow. For context, divozilimab is a humanized anti-CD20 monoclonal antibody engineered to enhance antibody-dependent cellular cytotoxicity through modified Fc glycosylation. It was previously approved in Russia in 2023 for relapsing multiple sclerosis (MS) and systemic sclerosis.

AQUARELLE (NCT05730699) is an open-label, multicenter, phase 3 study enrolling patients with seropositive and seronegative NMOSD, who receive divozilimab 500 mg intravenously every 24 weeks over a planned treatment duration of 3 years. The 1-year analysis included 105 enrolled patients.

Efficacy endpoints included adjudicated annualized relapse rate (ARR), the proportion of relapse-free patients, change in Expanded Disability Status Scale (EDSS) score, and freedom from 3-month confirmed disability worsening (CDW). Because AQUARELLE has no internal placebo arm, investigators compared outcomes against a historical placebo arm from the SAkuraStar trial using a matching-adjusted indirect comparison.

At 1 year, the ARR was 0.104 (95% CI, 0.056-0.193), and 90.5% of patients remained relapse-free. In the indirect comparison with the SAkuraStar historical placebo arm, divozilimab was associated with a significantly lower risk of relapse (weighted hazard ratio, 0.108; 95% CI, 0.036-0.324; P <.001), and the weighted ARR ratio for divozilimab versus historical placebo was 0.237 (90% CI, 0.084-0.672). Notably, no patients experienced EDSS progression or 3-month CDW over the follow-up period.¹

Adverse events (AEs) were reported in 76.2% of patients and were predominantly mild to moderate. The most common treatment-related adverse events (AEs) were lymphopenia (21.0%), neutropenia (12.4%), leukopenia (11.4%), and infusion-related reactions (5.7%).

The 1-year data follow an earlier 6-month readout from AQUARELLE, published in Multiple Sclerosis and Related Disorders, which compared outcomes against a different historical placebo arm, from the N-MOmentum trial. At 6 months, 94.3% of the same 105 patients were relapse-free, the ARR was 0.124 (95% CI, 0.056-0.276), and the weighted ARR ratio versus the N-MOmentum placebo arm was 0.172 (90% CI, 0.083-0.359). All patients were free of 3-month CDW at that point, and the SF-36 physical component score improved by approximately 3 points.²

Treatment-related AEs were reported in 35.2% of patients through 6 months, including 3 severe events (2.9%): decreased lymphocyte count, decreased neutrophil count, and an infusion reaction. No serious treatment-related adverse events were reported.

Divozilimab's approval in relapsing multiple sclerosis

Divozilimab's development in NMOSD builds on its approval in Russia for relapsing multiple sclerosis, based on the phase 3 MIRANTIBUS trial. In that 2-year, randomized, double-blind, double-dummy study, 338 patients with relapsing MS were assigned to divozilimab or teriflunomide; the adjudicated ARR at 48 weeks was 0.05 with divozilimab versus 0.13 with teriflunomide, a significant reduction (ratio, 0.39; 97.5% CI, 0.20-0.77; P =.0021), and treatment-related AEs occurred in 33.1% of the divozilimab group.³

Russia's Ministry of Health registered the drug, under the brand name Ivlizi, as the country's first domestically developed original drug for multiple sclerosis in 2023.⁴ Divozilimab was subsequently approved there for systemic sclerosis in 2025, based on 48-week data from the phase 3 LIBERIUS trial.⁵

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REFERENCES
1. Boyko A, Boyko O, Zakharova M, et al. One-year efficacy and safety of divozilimab in patients with neuromyelitis optica spectrum disorders: results from the phase III AQUARELLE study. Abstract 1805. Presented at: 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026); October 21-23, 2026; Toronto, Ontario, Canada.
2. Boyko A, Boyko O, Sivertseva S, et al. Divozilimab in patients with neuromyelitis optica spectrum disorders: 6 months results of AQUARELLE study. Mult Scler Relat Disord. Published online 2026. doi:10.1016/j.msard.2026.107608
3. Boyko A, Linkova Y, Zinkina-Orikhan A, Porozova A. New anti-CD20 divozilimab in relapsing multiple sclerosis: phase III MIRANTIBUS trial results. Mult Scler Relat Disord. 2023. doi:10.1016/j.msard.2023.105169
4. Biocad's therapy for multiple sclerosis has been registered by the Ministry of Health. gxpnews. Published April 1, 2023. Accessed October 20, 2026. https://gxpnews.net/en/2023/04/biocads-therapy-for-multiple-sclerosis-has-been-registered-by-the-ministry-of-health/
5. Ministry of Health approves divozilimab for systemic scleroderma for the first time [in Russian]. gxpnews. Published March 19, 2025. Accessed October 20, 2026. https://gxpnews.net/2025/03/minzdrav-vpervye-odobril-divozilimab-dlya-lecheniya-sistemnoj-sklerodermii/