ECTRIMS Studies Showcase Treatment Benefits of Ofatumumab for NMOSD

At the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, a pair of abstracts demonstrated the therapeutic potential of ofatumumab (Kesimpta; Novartis), a next-generation CD20 monoclonal antibody, as a treatment for neuromyelitis optica spectrum disorder (NMOSD).^1,2

The first study, a retrospective multicenter trial spanning 15 tertiary hospitals in China, comprised 112 patients with NMOSD who received ofatumumab treatment for 1.7 (IQR, 1.1-2.0) years. Led by Chao Zhang, of Beijing Tiantan Hospital, Capital Medical University, the trial aimed to evaluate efficacy and safety of ofatumumab using annualized relapse rate (ARR) as the primary outcome.¹

Overall, findings showed a median ARR decline from 2.0 (IQR, 0.7-10.0) before ofatumumab to 0 (IQR, 0.0-0.0; P <.001) at the time of the study completion. Among 22 patients (20%) who experienced a total of 25 relapses, the majority occurred within the first treatment year and were predominantly minor events (76%). Change in Expanded Disability Status Scale (EDSS) score, a secondary outcome, was decreased at last follow-up (median: pre-treatment: 3.5 [IQR, 2.0-6.5]; post-treatment: 2.0 [IQR, 1.0-3.5]; P <.001).

Ofatumumab, a fully human anti-CD20 monoclonal antibody, was approved in 2020 as a treatment for relapsing multiple sclerosis (MS). Like rituximab and inebilizumab, medications both used for NMOSD, it depletes circulating CD20+ B cells, thereby reducing the population of cells that can mature into antibody-secreting plasma cells. To date, ofatumumab has yet to be formally tested in large-scale NMOSD trials.

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Additional data from the study showed that 76% of patients on ofatumumab (n = 94) had decreases in aquaporin-4 (AQP4) IgG titer at the last follow-up. During ofatumumab treatment, 24 infections occurred in 20 patients (18%), the vast majority (92%) being grade 1–2. Two patients (2%) developed grade 3 pneumonia requiring hospitalization, while hypogammaglobulinemia was observed in 14% but showed no link to infection.

The second abstract was a prospective longitudinal study conducted from March 2022 to February 2025 testing the real-world efficacy and safety of ofatumumab in Chinese patients with NMOSD (n = 23) vs mycophenolate mofetil (MMF), a traditional NMOSD medication, as comparator. The study spanned 72 weeks, using time to first relapse as the primary end point and changes in EDSS and ARR post-enrollment as secondary outcomes.²

Led by Qiuming Zeng, of Xiangya Hospital, Central South University, China, 8.7% (2 of 23) of those on ofatumumab relapsed at last visit vs 36.8% (21 of 57) of those on MMF (HR, 0.218; 95% CI, 0.051-0.937; P = .041). Only those in the ofatumumab group showed improvements on EDSS, although the between-group differences were nonsignificant.

Additional data from the study revealed an ARR of 0.065 for the ofatumumab group, that represented a 75.7% reduction relative to the MMF cohort (group difference, –0.203; 95% CI, –0.344 to –0.061; P = .041). At week 72, study investigators noted significant decreases in cytomegalovirus-IgG, thyroglobulin antibody, and anti-thyroid peroxidase antibody levels among ofatumumab-treated patients. Within this cohort, adverse events were reported in 52.2% (12 of 23) of patients, with no serious adverse events attributed to the study treatment.

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REFERENCES
1. Zhu L, Yang X, Shi FD, Zhang C. Ofatumumab Treatment in Patients with Neuromyelitis Optica Spectrum Disorder. Presented at: ECTRIMS 2025; September 24-26; Barcelona, Spain. ABSTRACT P858
2. Yang H, Jiang F, Cai H, et al. Efficacy and Safety of Ofatumumab in the Treatment of NMOSD: A Multi-Center Prospective Study. Presented at: ECTRIMS 2025; September 24-26; Barcelona, Spain. ABSTRACT O135