Zeposia (ozanimod) / BMS - LARVOL DELTA

To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=195 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Mar 2025 ➔ Oct 2025 | Trial primary completion date: Mar 2025 ➔ Oct 2025

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

Obesity Is Associated with Inferior Clinical Treatment Outcomes in Inflammatory Bowel Disease: A Nationwide Dutch Registry Study. (PubMed, Dig Dis Sci) - "Obesity was associated with lower steroid-free clinical remission at week 24. Obese patients with IBD should be encouraged to lose weight not only to improve their overall health, but also to optimize their treatment outcomes."

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

A Study to Evaluate the Efficacy, Safety, and Drug Levels of Oral Ozanimod in Pediatric Participants With Moderately to Severely Active Crohn's Disease With an Inadequate Response to Conventional Therapy (clinicaltrials.gov) - P2/3 | N=5 | Terminated | Sponsor: Bristol-Myers Squibb | Completed ➔ Terminated; Study was terminated due to business reasons.

Trial termination • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Pediatrics

Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand. (PubMed, Int J Mol Sci) - "In isolated B cells stimulated with a TLR9 ligand, ozanimod reduced cell surface expression of CD69, CD86, and CD40, as well as TNF and IL-6 accumulation in supernatant. We conclude that lymphocyte subsets are functionally impacted in patients with fibrotic hypersensitivity pneumonitis and that ozanimod can interfere ex vivo with the overactivation of B cells and CD8 T cells in response to specific stimuli."

IO biomarker • Journal • Preclinical • Fibrosis • Immunology • Inflammation • Pneumonia • Pulmonary Disease • CD40 • CD69 • CD8 • CD86 • IL4 • IL6

Contribution of S1pr1 -featured astrocyte subpopulation to cisplatin-induced neuropathic pain. (PubMed, bioRxiv) - "The functional S1PR1 antagonist, ozanimod, prevented cisplatin-induced neuropathic pain and astrocytic upregulation of the Wnt signaling pathway genes. These data not only highlight FGFR3 as one of the astrocytic targets of S1PR1 but raise the possibility that S1PR1-induced engagement of Wnt signaling in S1pr1 high astrocytes may contribute to CIPN. Overall, our results provide a comprehensive mapping of cellular and molecular changes engaged in cisplatin-induced neuropathic pain and decipher novel S1PR1-based mechanisms of action."

Journal • Genito-urinary Cancer • Neuralgia • Oncology • Ovarian Cancer • Pain • Peripheral Neuropathic Pain • Solid Tumor • Testicular Cancer • FGFR3 • S1PR1

A Study to Assess the Effectiveness and Safety of Ozanimod in Chinese Adults With Relapsing Multiple Sclerosis (clinicaltrials.gov) - P4 | N=84 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

The Role of Patient-Reported Outcomes in US FDA Novel Drug Approvals and Reimbursement Decisions (2020-2024) (ISPOR 2025) - "Rinvoq (AbbVie) - PRO data showed improved quality of life in rheumatoid arthritis, contributing to $2.3 billion...Zeposia (Bristol-Myers Squibb) - PROs on fatigue reduction generated $500 million. Imcivree (Rhythm Pharmaceuticals) - PRO data supported FDA approval 2022: FDA : 37 drugs, with 30% (11 drugs) Reimbursement : 85 total approvals, with 35% (30 approvals) Adbry (LEO Pharma) - PROs on itch reduction generated $90 million . Camzyos (Bristol-Myers Squibb) - Symptom relief PROs were key 2023: FDA : 49 drugs, with 33% (16 drugs) Reimbursement 95 total approvals, with 45% (43 approvals. Leqembi (Eisai/Biogen) - FDA approval and Medicare conditional reimbursement for Alzheimer's disease leveraged PROs on cognitive function improvements, generating $200 million/ Jaypirca (Eli Lilly) - Patient-reported symptom relief supported FDA and payer decisions for mantle cell lymphoma... The inclusion of PROs in FDA novel drug approvals increased from 18% in 2020 to 40% in..."

Clinical • Patient reported outcomes • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders • Fatigue • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lymphoma • Mantle Cell Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology

Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence. (PubMed, Pharmaceuticals (Basel)) - "Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators."

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

Lymphopenia associated with sphingosine 1-phosphate receptor modulators (S1PRMs) in multiple sclerosis: analysis of European pharmacovigilance data. (PubMed, Pharmacol Rep) - "The most relevant clinical implication of the disproportionality analysis is to increase the awareness of the risk of lymphopenia related to these drugs, thus supporting proactive monitoring and optimizing treatment strategies for people with MS."

Adverse events • Journal • CNS Disorders • Multiple Sclerosis

Effect of Sphingosine 1 Phosphate Receptor Modulators on Fatigue Among Multiple Sclerosis Patients (P6-1.017). (PubMed, Neurology) - "We found 5 studies, 3 of which were randomized to injectable DMT, Standard DMT (interferon and glatiramer acetate), and teriflunomide, respectively...Fingolimod and ponesimod were found to be effective in improving fatigue among PwMS; no studies have been found on ozanimod and Siponimod...The institution of Dr. Bernitsas has received research support from Roche/Genentech."

Clinical • Journal • Review • CNS Disorders • Fatigue • Multiple Sclerosis

Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase. (PubMed, Org Lett) - "In this study, an imine reductase mutant (IR262-F185E/F229L) was identified with high enantioselectivity toward various N-hydroxyethyl imino derivatives. Furthermore, a continuous fed-batch strategy was designed to avoid the hydrolysis of imines, and up to 200 mM 1-((2-hydroxyethyl)imino)-2,3-dihydro-1H-indene-4-carbonitrile could be completely converted into (S)-1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-indene-4-carbonitrile in 70% isolated yield and >99% ee, demonstrating a great potential for the synthesis of the ozanimod intermediate in industrial applications."

Journal

Assessment of Real-World Adverse Events Associated with Ozanimod in Relapsing Remitting Multiple Sclerosis (RRMS) (ISPOR 2025) - "AE reports and patient outcomes were extracted for all instances where DMTs (ozanimod, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, teriflunomide, cladribine, alemtuzumab, natalizumab, ocrelizumab, ublituximab, and ofatumumab) were the 'primary suspect' for the AE... Based on this descriptive analysis of the FAERS data, ozanimod has a lower proportion of AEs linked to serious outcomes than the other DMTs. Ozanimod generally had a larger share of the ten labeled AEs compared with the other DMTs; however, these labeled AEs made up a small percentage of all the AEs reported for ozanimod and the other DMTs."

Adverse events • Clinical • Real-world • Real-world evidence • Back Pain • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Pain • Respiratory Diseases

A Study to Evaluate Efficacy and Long-term Safety of Oral Ozanimod in Chinese Participants With Moderately to Severely Active Ulcerative Colitis (UC) (clinicaltrials.gov) - P3 | N=131 | Terminated | Sponsor: Bristol-Myers Squibb | Trial completion date: Apr 2027 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Apr 2027 ➔ Mar 2025; Business objectives have changed

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

Ozanimod-associated macular edema. (PubMed, Can J Ophthalmol) - No abstract available

Journal • Macular Edema • Ophthalmology

Study to Evaluate the Effectiveness and Safety of Ozanimod Compared to Fingolimod in Children and Adolescents With Relapsing Remitting Multiple Sclerosis (clinicaltrials.gov) - P3 | N=194 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

A Lactation Study in Women Receiving Treatment With Ozanimod (clinicaltrials.gov) - P4 | N=16 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study. (PubMed, Neurol Clin Pract) - "We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs...Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections."

Adverse events • Journal • Real-world evidence • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Varicella Zoster

An Extension Study of Oral Ozanimod for Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P3 | N=854 | Terminated | Sponsor: Celgene | Completed ➔ Terminated; Business objectives have changed

Trial termination • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

A Study of Ozanimod in Pregnant Women With Ulcerative Colitis and Their Offspring (clinicaltrials.gov) - P=N/A | N=1182 | Not yet recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jun 2032 ➔ Jun 2033 | Trial primary completion date: Jun 2032 ➔ Jun 2033

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

Retrospective Analysis of CD20-Directed Cytolytic Antibody Treatment Switches to Ozanimod in Patients with Relapsing Multiple Sclerosis (MS) (ACTRIMS Forum 2025) - "To assess the rationale and methodology for cessation of a CD20-directed cytolytic antibody therapy (ocrelizumab, ofatumumab, rituximab, or ublituximab), who later transitioned to ozanimod.2... Switching from a CD20-directed cytolytic antibody therapy to ozanimod was driven by patient preference, recurrent infections, and physical/cognitive disability progression. Patient preference, desire to be on an oral medication, and perception that patients may experience less infections were top reasons for transitioning to ozanimod. Most patients transitioned in less than 4 months (IV formulation) and in less than 3 months (SC formulation), with 92% experiencing no adverse events."

Retrospective data • CNS Disorders • Cognitive Disorders • Developmental Disorders • Infectious Disease • Multiple Sclerosis • Pain • Respiratory Diseases • CD20

Guselkumab (Tremfya) for ulcerative colitis. (PubMed, Med Lett Drugs Ther) - No abstract available

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

IMPACT OF OZANIMOD (OZA) ON CIRCULATING NEUTROPHILS: RESULTS FROM THE PHASE 3 JAPANESE TRUE NORTH (J-TN) STUDY OF PATIENTS (PTS) WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS (UC) (DDW 2025) - No abstract available

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

Effect of Sphingosine 1 Phosphate Receptor Modulators on Fatigue Among Multiple Sclerosis Patients (AAN 2025) - "We found 5 studies, 3 of which were randomized to injectable DMT, Standard DMT (interferon and glatiramer acetate), and teriflunomide, respectively. Fingolimod and ponesimod were found to be effective in improving fatigue among PwMS; no studies have been found on ozanimod and Siponimod. As fatigue has a complex and subjective nature, more studies are required."

Clinical • CNS Disorders • Fatigue • Multiple Sclerosis

Characterization of Neurological Biomarkers in Patients with Early Relapsing Multiple Sclerosis and Comparison to Healthy Controls: Year 1 Interim Analysis of the ENLIGHTEN Study of Ozanimod (AAN 2025) - P3 | "In ENLIGHTEN patients, early treatment with ozanimod significantly decreased markers of axonal and neuronal damage at 1 year compared with baseline and normalized NfL levels to those of healthy controls, indicating slowed disease activity."

Biomarker • Clinical • CNS Disorders • Multiple Sclerosis • GFAP • NEFL

Whole Brain, Cortical Grey Matter, and Thalamic Volume Changes During 5–7 Years of Ozanimod in Relapsing MS: Final Results from the DAYBREAK Open-label Extension Study (AAN 2025) - P3 | "Ozanimod treatment led to decreased BVL during SUNBEAM/RADIANCE, which was sustained with continuous treatment up to 5 years in the OLE. Switching from IFN to ozanimod consistently reduced rates of BVL; participants continuously treated with ozanimod had lower WBV loss."

Clinical • CNS Disorders • Multiple Sclerosis