New Anti-Cd20 Divozilimab in Relapsing Multiple Sclerosis: Phase III MIRANTIBUS Trial Results

• Published in: Multiple sclerosis and related disorders 2023-12, Vol.80, p.105169, Article 105169
• Main Authors: Boyko, Alexey, Linkova, Yulia, Zinkina-Orikhan, Arina, Porozova, Anastasia
• Format: Article
• Language: English
• ISSN: 2211-0348
• DOI: 10.1016/j.msard.2023.105169

Divozilimab (DIV) was developed as an original humanized afucosylated monoclonal antibody against CD20. MIRANTIBUS is a 2-year randomized double-blind double-dummy study in subjects with relapsing multiple sclerosis (RMS). Subjects were randomized at a ratio of 1:1 to receive DIV 500 mg as intravenous infusions every 24 weeks or teriflunomide (TRF) 14 mg peroral daily. Two placebos were used to maintain blinding. Efficacy endpoints included annualized relapse rate (ARR) after 48 weeks of therapy (primary endpoint), dynamics of Expanded Disability Status Scale (EDSS) and quality of life (QoL) scales (European Quality of Life 5 Dimensions 3 Level Version, EQ-5D; Multiple Sclerosis Quality of Life 54 item, MSQOL-54). A total of 338 subjects were randomized (169 subjects per each group), and 321 subjects completed 48 weeks of therapy. The adjudicated ARR was 0.05 [95% CI, 0.03 - 0.09] with DIV and 0.13 [95% CI, 0.09 - 0.18] with TRF. DIV was superior to TRF in terms of ARR (DIV/TRF ratio was 0.39 [97.5% CI, 0.20 - 0.77], p = 0.0021). DIV significantly reduced the risk of relapses: the hazard ratio for time to first relapse between DIV and TRF was 0.48 [95% CI, 0.25–0.92]. After 48 weeks of treatment, the proportion of subjects with EDSS improvement was higher with DIV (17.2%) than with TRF (11.8%). Over 1 year of therapy, there were no worsening of QoL parameters in both DIV and TRF groups. Overall, 33.1% of subjects experienced adverse events (AE) related to treatment with DIV. The most common treatment-related AE in DIV group were lymphocyte count decrease (10.7%), infusion-related reactions (9.5%), neutrophil count decrease (7.7%) and leukocyte count decrease (6.5%). MIRANTIBUS study met its primary endpoint showing highly statistically significant reduction of ARR. DIV minimized neurological damage and has an acceptable safety profile.