Zeposia (ozanimod) / BMS - LARVOL DELTA

Eight-Point Change in Symbol Digit Modalities Test Scores: Findings From the Phase 3 SUNBEAM and DAYBREAK Ozanimod Trials Stratified by Sex (ECTRIMS 2025) - P3 | "These data align with previous studies showing male pts with RMS have slightly worse CPS than female pts (Uher T et al. Neurology 2020; 94:4243) .** Long-term OZA treatment appears to protect against cognitive decline, supporting its early use in pts with RMS regardless of sex."

P3 data • CNS Disorders • Multiple Sclerosis

Real-World Clinical Effectiveness and Safety of Ozanimod for Relapsing-Remitting Multiple Sclerosis in Germany: An Interim Analysis of the Prospective, Noninterventional OzEAN Study (ECTRIMS 2025) - P | "In this interim analysis of the real-world OzEAN study, ozanimod treatment was associated with a low relapse rate, stable disability, and stable/improved cognitive processing speed after approximately 2 years of treatment. The overall safety profile of ozanimod was consistent with the phase 3 clinical trials, except for a slightly higher rate of TEAEs leading to treatment discontinuation, consistent with other real-world studies of disease-modifying therapies."

Clinical • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Influence of Baseline Scores, Education Level, and Sex on 8-point Change in Symbol Digit Modalities Test Scores in Patients With Early Relapsing Multiple Sclerosis: Year 1 Interim Analysis of the Ozanimod Open-Label ENLIGHTEN Study (ECTRIMS 2025) - P3 | "After 1 year of ozanimod in ENLIGHTEN, most patients had improved or stable SDMT scores, with lower baseline SDMT scores, but not education level or sex, being associated with 8-point improvement on the SDMT. These interim findings support the use of ozanimod early in the treatment of patients with RMS"

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

Real-world experience with second-generation S1P receptor modulators in relapsing multiple sclerosis: a prospective observational study (ECTRIMS 2025) - "Ponesimod and Ozanimod showed expected lymphopenia while maintaining clinical-radiological stability. Patient-reported outcomes were generally stable, with fatigue and SDMT worsening observed in a number of cases."

Clinical • Observational data • Real-world • Real-world evidence • CNS Disorders • Fatigue • Multiple Sclerosis

Real-World Experience with Ozanimod at Two Academic Centers Across Two Years (ECTRIMS 2025) - "This retrospective analysis of a real-world ozanimod cohort included PwMS who were older and had longer disease duration than in the pivotal trials. Despite this, ozanimod showed good effectiveness and tolerability, especially at 2 years."

Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Disorders • Hypertension • Infectious Disease • Multiple Sclerosis • Respiratory Diseases

Real-World Comparison of Cladribine and S1P-Receptor Modulators in Treatment-Naive Relapsing MS: A Propensity Score-Matched Study (ECTRIMS 2025) - " This retrospective analysis included treatment-naïve RRMS individuals who were first treated with cladribine or S1PRMs (fingolimod, ozanimod, ponesimod) across 108 Italian specialist centres between 2011 and 2021. Cladribine was more effective in reducing disability progression despite comparable short-term NEDA-3 outcomes. However, its effectiveness in preventing relapses declined after 36 months of follow-up, suggesting a potential need for re-treatment or a therapy switch within three years to sustain long-term disease control."

Clinical • Real-world • Real-world evidence • Multiple Sclerosis

Long-Term Brain Atrophy in Female and Male Patients with Relapsing Multiple Sclerosis in the SUNBEAM, RADIANCE, and DAYBREAK Trials of Ozanimod (ECTRIMS 2025) - P3 | "Pts in the OZA arms had significantly lower atrophy rates than pts in the IFN arm and this efficacy was sustained through M84 for WBV and M60 for TV and CGMV. Similar trends were observed in each sex group, with more pronounced differences between OZA and IFN arms among female patients than among male patients. There was a trend toward slightly higher brain atrophy rates in male vs."

Clinical • CNS Disorders • Multiple Sclerosis

Ozanimod Reduces axonal Damage and CNS-restricted and peripheral blood inflammation in RRMS: Soluble Biomarkers Analysis from AppreZiate RWE Study (NCT05811416) (ECTRIMS 2025) - P | "These results show that ozanimod treatment is associated with reduced levels of sNfL suggesting neuroprotective effects. It also induces a reduction of serum GFAP and Il-17 values thus suggesting a down- regulation of innate and adaptive inflammation. Finally, it associates with an increase in IL-35 levels indicate that ozanimod exerts significant immunomodulatory functions, promoting a shift towards an anti- inflammatory profile."

Biomarker • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • GFAP • IFNG • IL10 • IL17A • IL6 • NEFL

Real World Clinical Data of Persistence, Effectiveness and Safety of Ozanimod Treatment in RRMS Patients in Spain: Interim Analysis of the AppreZiate Study (ECTRIMS 2025) - "Mean age at RRMS symptom onset was 38.7 years (SD 10,29); ozanimod initiation occurred at a mean age of43.5 years (SD 10,08) .** At ozanimod initiation, 96,7% (84) of patients were treatment-naïve and 3 patients had received some previous treatment (2 patients teriflunomide and 1 patient subcutaneous interferon β 1b) . The intermediate analysis of the AppreZiate study suggests that ozanimod demonstrates to be an effective treatment showing high persistence rates, favorable safety profiles, and effectiveness in patients with RRMS with low to moderate activity. Further follow-up is ongoing to consolidate findings."

Clinical data • Real-world • Real-world evidence • CNS Disorders • Infectious Disease • Multiple Sclerosis • IFNB1

Neutropenia in patients treated with anti-CD20 monoclonal antibodies for central nervous system inflammatory diseases: a single-center retrospective analysis (ECTRIMS 2025) - " 10 patients, 9/10 with MS and 1/10 with NMOSD, with one or more episodes of grade 3/4 neutropenia were identified (8 in ocrelizumab, 3 in ofatumumab, 1 in rituximab)...4/10 had recurrence of neutropenia after ocrelizumab rechallenge: 2 were directly shifted to ozanimod and teriflunomide, other 2 were shifted to ofatumumab with further neutropenia recurrence and subsequently shifted to natalizumab and ozanimod... Grade 3 or 4 neutropenia can be a complication of all anti-CD20, ranging from asymptomatic episodes with spontaneous resolution to febrile neutropenia requiring G-CSF treatment. It can be either monophasic or relapsing and in this case shift to another anti-CD20 equally exposes to recurrence risk, due to a possible ' class-effect ' ."

Retrospective data • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Inflammation • Neuromyelitis Optica Spectrum Disorder • Neutropenia

Evaluating Cognitive Outcomes in Multiple Sclerosis: Real-World Impact of Ozanimod on Processing Speed Using BICAMS (ECTRIMS 2025) - "This real-world study suggests that ozanimod treatment is associated with significant improvement in information processing speed, independent of traditional prognostic factors. These findings complement existing clinical trial data and warrant further investigation through larger, multicenter studies with extended follow-up periods to validate these cognitive benefits."

Clinical • Real-world • Real-world evidence • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

Differential Impact of Ozanimod on Lymphocyte Subsets in Patients with Early Relapsing Multiple Sclerosis in the ENLIGHTEN Study (ECTRIMS 2025) - P3 | "The differential effects of ozanimod on circulating levels of immune cells permit inhibition of inflammation while maintaining immune surveillance. These results expand upon earlier findings in patients with RMS and Crohn ' s disease, which illustrated that the effects of ozanimod on lymphocyte subsets occurs by 3 months and remains stable with further treatment."

Clinical • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammation • Multiple Sclerosis • CD4 • CD8

Different Definitions of Confirmed Disability Progression and Their Association With Brain Atrophy in Patients With Relapsing Multiple Sclerosis Treated With Ozanimod for up to 8 Years in the Phase 3 SUNBEAM/RADIANCE and Open-label DAYBREAK Studies (ECTRIMS 2025) - P3 | "After approximately 8 years of ozanimod treatment, less than 4% of patients reached SEDSS-6. Atrophy rates varied across CDP definitions, but all CDP definitions and RAW and PIRA were associated with whole brain and thalamic atrophy."

Clinical • P3 data • CNS Disorders • Multiple Sclerosis • IFNB1

Efficacy and safety of Ozanimod in real-world clinical practice: An observational study of a spanish patient cohort (ECTRIMS 2025) - "Prior disease-modifying therapy (DMT) included interferons (21.5%) , glatiramer acetate (9.8%) , and dimethyl fumarate (29.4%)... Ozanimod shows good safety, tolerability, and efficacy in real-world patients with moderately active RMS, consistent with pivotal trial results."

Clinical • Observational data • Real-world • Real-world evidence • CNS Disorders • Diabetes • Herpes Simplex • Infectious Disease • Macular Edema • Metabolic Disorders • Multiple Sclerosis • Ophthalmology • Respiratory Diseases

Preservation of Cortical Thickness in Relapsing Multiple Sclerosis Patients Treated with Ozanimod Up to 7 Years (ECTRIMS 2025) - P3 | "OZA showed a potential protective effect on CT during the phase 3 studies when compared to IFN. Switching to OZA also reversed the rates of CT reduction in pts initially on IFN. OZA effect on CT was sustained up 7 years."

Clinical • CNS Disorders • Multiple Sclerosis

Association of Pretreatment Lateral Ventricular Volume and Medulla Oblongata Volume with Cognitive Function After 1 Year of Ozanimod in Early Relapsing MS (ECTRIMS 2025) - P3 | "Trends suggested patients with early RMS who had smaller LVV and larger MOV at baseline were less likely to be cognitively impaired after 1 y of ozanimod than patients who started with larger LVV or smaller MOV. For some outcomes, middle tertiles were inconsistent with the trend (although 95% CIs overlapped) , which may in part stem from unidentified factors preferentially impacting cognitive function in one tertile or another."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

Ozanimod Normalizes Pro-Inflammatory Astrocyte Marker Gbp2 in MS Patient iPSC Derived Cerebral Organoid Models (ECTRIMS 2025) - "Our work shows that iPSC-derived cerebral organoids are valuable for evaluating drug impacts on human CNS cells. Comparing organoids from healthy and MS patient iPSCs can help characterize disease pathophysiology, as we found a bias towards excitatory neuron production in MS. Most excitingly, we found a potential new mechanism of action of ozanimod as it relates to MS astrocyte biology."

Clinical • Inflammation • Multiple Sclerosis • Solid Tumor • GBP2 • PAX6 • PDGFRA • PLP1 • SLC2A1

Acute Paroxysmal Dystonia as a Manifestation of Multiple Sclerosis Relapse due to Demyelinating Lesion in Basal Ganglia: A Case Report and Pathophysiological Insights. (ECTRIMS 2025) - P3 | "After 1 year of ozanimod in ENLIGHTEN, most patients had improved or stable SDMT scores, with lower baseline SDMT scores, but not education level or sex, being associated with 8-point improvement on the SDMT. These interim findings support the use of ozanimod early in the treatment of patients with RMS."

Case report • Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dystonia • Movement Disorders • Multiple Sclerosis

Product Theatre 2: Ozanimod, Separating from the Crowd, Insights on Safety (ECTRIMS 2025) - No abstract available

Clinical

Role of Age in the Austrian Multiple Sclerosis Treatment Registry (ECTRIMS 2025) - "Objectives/Aims: To evaluate the efficacy and safety of Alemtuzumab (AZM) , Cladribine (CLAD) , Dimethyl fumarate (DMF) , Fingolimod (FTY) , Natalizumab (NTZ) , Ocrelizumab (OCR) , Ofatumumab (OFA) , Ozanimod (OZA) , Ponesimod (PONE) , Siponimod (SIPO) , and Teriflunomide (TERI) in MS patients across different age groups... Our findings indicate that approximately one-third of treated MS patients in our registry are aged 50 years or older, underscoring the substantial presence of older patients within the treated MS cohort. Furthermore, efficacy outcomes (ARR and EDSS progression) were comparable between younger and older patients. These findings should be integrated into treatment strategies for older MS patients, considering the impact of immunosenescence and the increasing prevalence of comorbidities with advancing age."

CNS Disorders • Multiple Sclerosis

Ozanimod, Separating from the Crowd, Insights on Safety (ECTRIMS 2025) - No abstract available

Clinical

S1P Receptor Modulators Improve Clinical Outcomes in Ulcerative Colitis: A Stratified Meta-Analysis By Prior Biological Use, Corticosteroid Exposure, and Disease Characteristics. (PubMed, J Clin Gastroenterol) - "S1P modulators improved remission rates and secondary outcomes in UC with a generally favorable safety profile. More data on CD are needed."

Clinical data • Journal • Retrospective data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

COMPARATIVE RISK OF ADVANCED BIOLOGICAL AGENTS FOR SERIOUS INFECTIONS IN PATIENTS WITH ULCERATIVE COLITIS: ANALYSIS FROM REAL WORLD COHORT (UEGW 2025) - "Introduction: We conducted a retrospective cohort study to evaluate the risk of serious infections in patients with Ulcerative Colitis (UC) initiating advanced biological or small molecule therapies Aims & Using a large U.S. administrative, Optum Labs® database, we identified adult UC patients who initiated treatment with either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), S1PR modulators (ozanimod), or Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) between 2016-2023. In this large real-world cohort of UC patients, initiation with newly developed efficaeous agents like JAK inhibitors and drugs inhibiting the IL-23 pathway was associated with a lower risk of serious infection compared to TNF antagonists."

Clinical • Metastases • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Ulcerative Colitis • IL12A • IL23A

EFFECT-1LAT: Describing Treatment Patterns and Creating an Updated Treatment Flow in an Ulcerative Colitis Population (clinicaltrials.gov) - P=N/A | N=4000 | Not yet recruiting | Sponsor: Pfizer

New trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

COMPARATIVE RISK OF ADVANCED BIOLOGICAL AGENTS FOR CARDIOVASCULAR AND THROMBOTIC EVENTS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: DATA FROM A REAL WORLD COHORT (UEGW 2025) - "The therapeutic agents included either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), Janus kinase (JAK) inhibitors (tofacitinib and upadacitinib), or S1PR modulators (ozanimod). In this large real-world IBD cohort, there was no difference in risk of adverse cardiovascular and thrombotic events between any biological agent or small molecule, in compairosn to TNF antagnoists."

Clinical • Metastases • Real-world • Real-world evidence • Cardiovascular • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Myocardial Infarction • Ulcerative Colitis • Venous Thromboembolism • IL12A • IL23A