Zeposia (ozanimod) / BMS - LARVOL DELTA

Therapeutic targeting of sphingosine-1-phosphate receptor 1 (S1PR1) in angioimmunoblastic T-cell lymphoma. (ASH 2025) - "The molecular landscape of AITL is characterized by frequent genomic alterationsin epigenetic regulators, including TET2, DNMT3A, and IDH2, as well as components of the T-cell receptor(TCR) signaling pathway...This, together with our observation of increased S1PR1 expression in humanRHOA G17V⁺ AITL tumor samples, identifies S1PR1 deregulation as a potentially relevant effector of theoncogenic effects of RHOA G17V in TFH cells.S1P receptor inhibitors, such as fingolimod (FTY720) and next-generation, more selective modulatorssuch as ozanimod, siponimod, and ponesimod, are FDA-approved for the treatment of multiple sclerosisand other autoimmune diseases...These findings definean S1PR1–STAT3 inflammatory loop that promotes survival and dissemination in RHOA G17V-driven AITLand identify this axis as a therapeutically actionable vulnerability.In summary, our preliminary data establish a mechanistic link between oncogenic RHOA signaling andS1PR1-mediated membrane receptor..."

IO biomarker • CNS Disorders • Hematological Malignancies • Immunology • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD4 • DNMT3A • IDH2 • IL6 • RHOA • S1PR1 • S1PR5 • TET2 • TNFA

Cerebellar Subregional Atrophy in Relapsing-Remitting Multiple Sclerosis: Stage-dependent Dynamics and Pharmacological Modulation. (PubMed, Brain Res Bull) - "This study demonstrated stage-specific patterns of cerebellar atrophy in RRMS and the heterogeneous, stage-dependent effects of DMTs on posterior cerebellar subregions. Lobules IX and VIIIb emerged as critical loci linking pharmacological modulation with cognitive outcomes. These findings suggest that these regions may serve as potential imaging biomarkers of therapeutic response and prognosis in MS."

Journal • CNS Disorders • Multiple Sclerosis

Addressing autoimmune comorbidities in multiple sclerosis: A case report of ulcerative colitis remission in a patient treated with cladribine tablets. (PubMed, Mult Scler) - "This case highlights cladribine's potential in managing both MS and UC, though its efficacy faded over time. Further research into shared immunopathogenesis and therapeutic strategies in co-existing autoimmune diseases is warranted."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis

Comparative Efficacy of Mesalazine and Ozanimod following Induction Treatment in Mesalazine-Exposed Advanced Therapy-Naïve Adult Ulcerative Colitis Patients. (PubMed, Inflamm Intest Dis) - "We compared the efficacy of oral mesalazine (Asacol) as monotherapy and ozanimod (Zeposia) as add-on therapy to mesalazine, without concomitant corticosteroids, following induction treatment in mesalazine-exposed but immunomodulator- and advanced therapy-naïve UC patients. A higher percentage of patients treated with ozanimod achieved endoscopic improvement (MES ≤1 without friability) compared to mesalazine (38% vs. 29%, p = 0.018). Among individuals previously exposed to mesalazine, a similar effect on clinical efficacy was observed between patients treated with mesalazine and those treated with ozanimod."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Selected aspects of epidemiology of multiple sclerosis in Poland: a multicenter pilot study. (PubMed, Neurol Neurochir Pol) - "This study highlights substantial progress in the diagnostic and therapeutic management of MS in Poland over the past 15 years. The widespread implementation of MRI and CSF analysis, alongside significantly improved access to DMTs, has contributed to notably better clinical outcomes. These improvements are reflected in reduced relapse rates, slower disability progression, and a decreased prevalence of secondary progressive MS."

Journal • CNS Disorders • Multiple Sclerosis

Effectiveness of Ozanimod in Patients With Steroid-Dependent Ulcerative Colitis (clinicaltrials.gov) - P=N/A | N=150 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New trial • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Small-molecule therapies for pediatric inflammatory bowel disease: toward precision medicine. (PubMed, World J Pediatr) - "Small-molecule therapies offer a promising and mechanistically precise direction for the management of pIBD. Future progress will depend on age-specific clinical trials, physiologically based pharmacokinetic modeling, and biomarker discovery through integrated multiomics. Collaborative multicenter research is essential to optimize the safety and efficacy of these agents in children."

Journal • Review • Cardiovascular • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Oncology • Pediatrics

A Lactation Study in Women Receiving Treatment With Ozanimod (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: Bristol-Myers Squibb | N=16 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

Late-onset severe neutropenia in patients with relapsing remitting multiple sclerosis treated with ocrelizumab: case report and literature review. (PubMed, Front Neurosci) - "Ocrelizumab was held, patient switched to ozanimod, but neutropenia recurred. A subsequent episode occurred 3 months later during confirmed rhinovirus infection, again resolving promptly. These cases highlight the unpredictable nature of recurrent LON with ocrelizumab and suggest the possibility of immune-mediated marrow suppression, potentially unmasked or worsened by infections, rather than direct drug toxicity, highlighting the need for clearer management guidelines."

Journal • CNS Disorders • Hematological Disorders • Immunology • Infectious Disease • Multiple Sclerosis • Neutropenia

Observational Study of the Effect of Ozanimod on Fatigue in Multiple Sclerosis Patients (clinicaltrials.gov) - P=N/A | N=26 | Terminated | Sponsor: Brigham and Women's Hospital | N=40 ➔ 26 | Not yet recruiting ➔ Terminated; Funding ended prematurely

Enrollment change • Trial termination • CNS Disorders • Fatigue • Multiple Sclerosis

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 | Trial completion date: Oct 2025 ➔ Mar 2026 | Initiation date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Oct 2025 ➔ Mar 2026

Trial completion date • Trial initiation date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for etrasimod. (PubMed, Front Pharmacol) - "A comparative analysis against fingolimod and ozanimod was performed to contextualize findings. The lack of unexpected signals remains reassuring. The frequent reporting of lack of efficacy highlights the need for close monitoring, and the comparative data offer valuable context for clinicians selecting S1P receptor modulator therapy."

Adverse events • Journal • Real-world evidence • Inflammatory Bowel Disease • Macular Edema • Ophthalmology • Pain

Sphingosine-1-Phosphate (S1P) Receptor Modulators for the Treatment of Inflammatory Bowel Disease (IBD): Mechanisms, Clinical Evidence, and Practical Insights. (PubMed, Biomedicines) - "Etrasimod and ozanimod are both licensed for moderate-to-severe ulcerative colitis and have both shown superiority over placebo, with emerging data for their use in Crohn's disease. By modulating immune cell distribution, without reducing overall immune function, they offer a highly favourable safety profile. This narrative review explores the pharmacology, safety and efficacy of sphingosine-1-phosphate receptor modulators based on clinical trials and real-world evidence and offers practical guidance on their initiation and monitoring."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Sphingosine-1-phosphate (S1P) signaling as a novel therapeutic target for alcohol abuse. (PubMed, bioRxiv) - "Specifically, we observed that two S1P receptor agonists FDA-approved for multiple sclerosis, fingolimod and ozanimod, and the more brain penetrant S1P 1 receptor agonist CYM5442, reduced binge alcohol drinking in the drinking in the dark (DID) paradigm in mice...Notably, CYM5442 was less aversive than naltrexone, an FDA-approved medication for the treatment of alcohol use disorder that shares a similar broad reducing action on alcohol intake and consummatory behavior...Lastly, gene expression analysis by RNA-Seq revealed that S1P regulates a complex set of genes in the transition to alcohol dependence. Overall, our results establish S1P signaling as a novel therapeutic target for alcohol use disorder."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Multiple Sclerosis

AppreZiate: A Study to Describe the Persistence With Ozanimod Treatment in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants (clinicaltrials.gov) - P=N/A | N=200 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Sep 2025 ➔ Nov 2026 | Trial primary completion date: Sep 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Once-Daily Oral Ozanimod for Japanese Patients With Ulcerative Colitis: Results From the Phase 2/3 J-True North Study. (PubMed, Gastro Hep Adv) - P3 | "This large-scale clinical trial demonstrated the efficacy and safety of once-daily oral ozanimod in Japanese patients with moderately to severely active ulcerative colitis. This is the first time that the efficacy and safety of ozanimod were verified in a large number of patients in Asia."

Journal • P2/3 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • S1PR1

Safety and Efficacy of Ozanimod in Patients With Moderately to Severely Active Ulcerative Colitis Stratified by Age. (PubMed, Inflamm Bowel Dis) - "Ozanimod safety was similar and efficacy was generally comparable across age groups, although statistical significance vs placebo was not achieved in patients >60 years of age."

Journal • Cardiovascular • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hypertension • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Macular Edema • Oncology • Ophthalmology • Rare Diseases • Ulcerative Colitis

Artificial Intelligence Analysis of Endoscopy Outperforms Conventional Endoscopic Scoring for Agreement with Symptoms and Quality of Life in a Phase 3 Ulcerative Colitis Trial. (PubMed, Am J Gastroenterol) - "AI-enabled endoscopic scoring has better agreement with symptomatic remission and HR-QoLs compared to MES and could quantitatively redefine adequate mucosal healing."

HEOR • Journal • P3 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Clinical sphingosine 1-phosphate receptor agonists protect oligodendrocytes in the cuprizone demyelination model (Neuroscience 2025) - "Both S1PR1- and S1PR5-selective agonists protected mature oligodendrocytes against cytokine-induced cell death in an in vitro oligodendrocyte model, suggesting that the mechanisms of protection in vivo are more complex.In conclusion, siponimod has direct neuroprotective actions in the CNS. As siponimod but not ozanimod protected against oligodendrocyte loss, it is likely that the protective effects of siponimod in vivo are mediated at least partially through S1PR5."

Clinical • CNS Disorders • S1PR1 • S1PR5

Cost-Effectiveness of Etrasimod, Ozanimod, and Adalimumab Compared to Infliximab in Treatment-Naive Patients With Moderate to Severe Ulcerative Colitis (ISPOR-EU 2025) - "These results suggest that, given similar life-years and QALYs across treatments, cost differences are the primary driver. In this analysis, infliximab emerged as the preferred first-line option due to its lower costs without compromising health outcomes."

Clinical • Cost effectiveness • HEOR • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Mucositis • Ulcerative Colitis

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Final analysis of the DAYBREAK open-label extension trial. (PubMed, Mult Scler) - P3 | "Long-term ozanimod treatment had a favourable safety and tolerability profile and provided sustained control of clinical and MRI disease activity in participants with RMS.Registries:ClinicalTrials.gov ID: NCT02576717; EudraCT: 2015-002500-91."

Journal • CNS Disorders • Herpes Zoster • Infectious Disease • Macular Edema • Multiple Sclerosis • Ophthalmology • Varicella Zoster • S1PR1

Comparative Effectiveness of Cladribine and S1P Receptor Modulators in Treatment-Naive Relapsing-Remitting MS. (PubMed, JAMA Netw Open) - "All treatment-naive patients with RRMS who initiated cladribine or an S1PRM (fingolimod, ozanimod, or ponesimod) between January 2011 and October 2021 and had at least 12 months of follow-up were included. These findings suggest cladribine was associated with superior effectiveness in reducing disability progression over 25 months, likely due to reduced PIRA, despite comparable short-term NEDA-3 outcomes. However, relapse prevention declined after 36 months, suggesting retreatment or therapy modification within 3 years may be needed to maintain long-term disease control."

Clinical • HEOR • Journal • CNS Disorders • Multiple Sclerosis

Successful Use of Ozanimod in a Patient With Overlapping Multiple Sclerosis and Crohn's Disease (ACG 2025) - "Humira was discontinued, and she was switched to Tysabri, which stabilized her MS...She was started on prednisone and ozanimod...Phase II STEPSTONE data showed clinical, endoscopic, and histological benefits2. In this case, ozanimod induced and maintained remission in both MS and CD, highlighting its potential as a dual-purpose therapy."

Clinical • Anemia • CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immune Modulation • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis • Ulcerative Colitis

Efficacy of Advanced Therapies for Naïve and Experienced Patients for Moderately-to-Severely Active Ulcerative Colitis: A Bayesian Network Meta-Analysis (ACG 2025) - "ADA, adalimumab; CrI, credible interval; ETS, etrasimod; FIL, filgotinib; GOL, golimumab; GUS, guselkumab; IFX, infliximab; MIR, mirikizumab; OZN, ozanimod; PBO, placebo; RR, relative risk; RZB, risankizumab; TOF, tofacitinib; UPA, upadacitinib; UST, ustekinumab; VDZ, vedolizumab. Four additional studies each for induction and maintenance were included. Results of pairwise comparisons across agents from the 2022 NMA were consistent. For additional agents, most pairwise comparisons had no significant difference at the end of induction and maintenance (Figs 1 & 2).For AT-N induction clinical remission, MIR 300mg was significantly less effective vs RZB 1200mg (RR, 0.7; 95% CrI, 0.5-1.0) and GUS 200mg was favored vs MIR 300mg (1.6, 1.1-1.2)."

Metastases • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

From Diverticular Disease to Ulcerative Colitis: A Case of Evolving Colonic Pathology (ACG 2025) - "Initial management included corticosteroids and mesalamine, followed by a transition to ozanimod; however, he continued to endure symptoms of rectal bleeding, urgency and worsening abdominal pain. He required multiple courses of prednisone to maintain functionality. He failed treatment with Infliximab, and as a result, therapy was escalated to combination treatment with upadacitinib and vedolizumab...B. Histology from biopsy of sigmoid colon taken during colonoscopy after presentation for abdominal pain and rectal bleeding with findings consistent with chronic mildly active colitis including crypt abscesses and epithelial cell neutrophil predominance."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Mucositis • Ulcerative Colitis