Real-World Ozanimod Data in Relapsing-Remitting MS Show Low Relapse Rates and Stable Disability Over 3 Years

A prospective, noninterventional study from Germany has provided 3-year real-world data on the effectiveness and safety of ozanimod (Zeposia; Bristol Myers Squibb) for relapsing-remitting multiple sclerosis (RRMS), suggesting low relapse activity, generally stable disability, and no new safety concerns in routine clinical practice.¹ The data comes from an abstract being presented at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 27-29, Charlotte, North Carolina.

The OzEAN study (NCT05335031) followed adults with confirmed RRMS treated with ozanimod 0.92 mg across 64 sites, evaluating real-world persistence as the primary outcome and assessing clinical effectiveness and safety over up to 36 months. The analysis included 398 patients, most of whom were female (69.4%), with a mean (SD) age of 40.3 (11.4) years and a mean disease duration of 6.0 (7.0) years since RRMS diagnosis. More than one-third (35.7%) were treatment naïve. Prior to study entry, patients had a mean of 0.8 (0.8) relapses in the year before screening. After 3 years of ozanimod exposure, the annualized relapse rate (ARR) was 0.10 (95% CI, 0.07-0.12), and 356 patients (89.4%) remained relapse free during a mean follow-up of 32.5 (11.4) months, indicating a low level of clinical disease activity in this real-world cohort.

Ozanimod persistence declined over time, but remained above 50% at 3 years. The probability of ozanimod persistence was 76% (95% CI, 72%-80%) at 12 months, 63% (59%-68%) at 24 months, and 54% (48%-59%) at 36 months. Disability as measured by the Expanded Disability Status Scale (EDSS) appeared largely stable at the group level: mean (SD) EDSS was 1.8 (1.3) at baseline (n = 350) and 2.0 (1.3) at 36 months (n = 102). Cognitive performance, assessed with the Symbol Digit Modalities Test (SDMT), showed a shift in the proportion of patients with scores suggestive of impairment. At baseline, the mean (SD) SDMT score was 52.8 (13.7), and 23.7% (75 of 317) had scores of 44 or lower. By 36 months, 13.8% (11 of 80) had SDMT scores of 44 or lower, suggesting a reduction in the proportion of patients with cognitive impairment among those with available follow-up data.

Adverse events were frequent but largely consistent with the known safety profile of sphingosine 1-phosphate receptor modulators. Treatment-emergent adverse events (TEAEs) occurred in 309 patients (77.6%). The most common TEAEs (≥5%) were lymphopenia (34.6%), nasopharyngitis (20.1%), COVID-19 (16.5%), coronavirus infection (12.3%), elevated gamma-glutamyl transferase (8.1%), increased liver function test results (8.1%), depression (7.8%), leukopenia (7.8%), increased alanine aminotransferase (7.1%), headache (7.1%), and central nervous system lesions (5.5%). TEAEs led to treatment discontinuation in 37 patients (9.3%), most often due to lymphopenia (4.5%), nasopharyngitis (2.6%), COVID-19 (2.3%), central nervous system lesions (1.9%), leukopenia (1.6%), and increased alanine aminotransferase (1.3%). Serious TEAEs were reported in 41 patients (10.3%).

Overall, in this 3-year, real-world German cohort, ozanimod use in RRMS was associated with low ARR, a high proportion of relapse-free patients, generally stable EDSS scores, and a lower proportion of patients with SDMT-defined cognitive impairment at follow-up, with no new safety signals reported by the investigators. Ozanimod is a sphingosine 1-phosphate receptor modulator that was approved by the FDA for relapsing MS in 2020.²

Notably, a 3 year ad hoc analysis from ENLIGHTEN (NCT04140305), a phase 3b clinical trial for ozanimod in adults with relapsing multiple sclerosis (RMS), are also being presented this year at CMSC.³ Notably, the analysis indicated that cognitive performance remained stable during long-term treatment with ozanimod in patients with RMS. Overall, investigators noted that these findings suggest that early identification of patients in the lowest whole brain volume tertile could help inform clinical counseling among adults with RMS. Furthermore, the results of the study suggested that reduced brain atrophy associated with earlier ozanimod initiation could potentially contribute to preservation of cognitive performance.

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REFERENCES
1. Buttman M, Becker VU, Fischer J, et al. Real-world effectiveness and safety of ozanimod for relapsing-remitting multiple sclerosis in the prospective noninterventional OzEAN study in Germany: 3-year results. Presented at: 2026 CMSC Annual Meeting; May 27-29; Charlotte, North Carolina. Abstract DMT04.
2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis. News release. Briston Myers Squibb. March 26, 2020. Accessed May 26, 2026. https://news.bms.com/news/corporate-financial/2020/US-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-ZEPOSIA-ozanimod-a-New-Oral-Treatment-for-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx
3. DeLuca J, Bergsland N, Dwyer M, et al. Relationship Between Cognitive Function and Brain Volume Outcomes in People With Relapsing Multiple Sclerosis in the Phase 3b ENLIGHTEN Study: 3-Year Results. Presented at: 2026 CMSC Annual Meeting; May 27-29; Charlotte, North Carolina. Abstract DMT30.