Zeposia (ozanimod) / BMS - LARVOL DELTA

ENLIGHTEN: Study Describing Cognitive Processing Speed Changes in Relapsing Multiple Sclerosis Subjects Treated With Ozanimod (RPC-1063) (clinicaltrials.gov) - P3 | N=188 | Terminated | Sponsor: Celgene | Trial completion date: Apr 2026 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ May 2025; Business objective has changed

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

Sphingosine-1-Phosphate Receptor Modulators for the Treatment of Ulcerative Colitis: A Narrative Review Focusing on Safety. (PubMed, United European Gastroenterol J) - "Safety data from the field of multiple sclerosis (MS) will be discussed because the first S1PR modulator to reach the market, fingolimod, was used extensively for relapsing-remitting MS. Indications for the safe use of ozanimod and etrasimod in ulcerative colitis patients will be provided."

Journal • Review • CNS Disorders • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis • Oncology • Solid Tumor • Ulcerative Colitis

Define Predictors of Response to Ozanimod in UC Discovering Biomarkers in the Management of Ulcerative Colitis (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Beth Israel Deaconess Medical Center | N=20 ➔ 0 | Trial completion date: Apr 2024 ➔ Dec 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Apr 2024 ➔ Dec 2024

Biomarker • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Glial Fibrillary Acidic Protein as a Marker of Disease in Relapsing Multiple Sclerosis: Post Hoc Analysis of Phase 3 Ozanimod Trials. (PubMed, Eur J Neurol) - P3 | "These data suggest that plasma GFAP is a relapse-independent metric of baseline disease severity and a predictor of treatment response in participants with RMS."

Biomarker • Clinical • Journal • P3 data • Retrospective data • CNS Disorders • Multiple Sclerosis • GFAP • IFNB1 • NEFL

A Lactation Study in Women Receiving Treatment With Ozanimod (clinicaltrials.gov) - P4 | N=16 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date

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

The Current Sphingosine 1 Phosphate Receptor Modulators in the Management of Ulcerative Colitis. (PubMed, J Clin Med) - "This narrative review aims to distil the key trial data on the efficacy and safety of ozanimod and etrasimod, the two S1PR modulators currently licensed for use in UC. We summarise their safety profiles, taking into consideration open label extension data. Finally, we consider where this class of drugs may be best placed in the treatment landscape and also provide a practical guide for their use in clinical practice."

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

PREVALENCE OF EXTRAINTESTINAL CUTANEOUS MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE IN NON-WHITE PATIENTS: A RETROSPECTIVE COHORT ANALYSIS (DDW 2025) - " In this retrospective cohort study, we used TriNetX, a healthcare database comprising over 119 million patients, to identify both White and non-White patients with a diagnosis of IBD who were prescribed at least one IBD-specific medication or advanced therapy including: Mesalamine, sulfasalazine, balsalazide, budesonide, azathioprine, methotrexate, 6-mercatopurine, infliximab, certolizumab, golimumab, adalimumab, vedolizumab, ustekinumab, tofacitinib, upadacitinib, risankizumab, mirikizumab, guselkumab, etrasimod, and ozanimod. With the rise of IBD in non-White populations, the representation of CM of IBD in this population is significantly limited, underrecognized, and thus undertreated. Our results reveal increased prevalence of several CM in the non-White IBD patient population. Notably, hidradenitis suppurativa has been shown to be associated with IBD, however our study is one of the first to highlight that it is significantly increased in IBD patients who are..."

Retrospective data • Cognitive Disorders • Dermatology • Dermatopathology • Gastroenterology • Gastrointestinal Disorder • Herpes Zoster • Hidradenitis Suppurativa • Immunology • Inflammation • Inflammatory Bowel Disease • Psoriasis • Varicella Zoster • Vasculitis • Vitiligo

RISK FOR RECURRENT VTE IN IBD PATIENTS ON ANTICOAGULATION FOR JAK INHIBITORS COMPARED TO OTHER THERAPIES (DDW 2025) - "This population was then divided into patients who were prescribed a JAKi (tofacitinib for ulcerative colitis (UC) or upadacitinib for either UC or Crohn's disease) or other IBD-specific medications including: Mesalamine, sulfasalazine, balsalazide, budesonide, azathioprine, methotrexate, 6-mercatopurine, infliximab, certolizumab, golimumab, adalimumab, vedolizumab, ustekinumab, and risankizumab, mirikizumab, guselkumab, etrasimod, and ozanimod. IBD is associated with an increased risk of VTE. The evidence of recurrent VTE for patients with JAKi use is limited. Current disclaimers for JAKi emphasize risks of use in patients with history of VTE."

Clinical • Cardiovascular • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Inflammatory Bowel Disease • Respiratory Diseases • Ulcerative Colitis • Venous Thromboembolism

NET REMISSION RATES WITH ADVANCED THERAPIES IN ULCERATIVE COLITIS: AN ANALYSIS OF PHASE 3 RANDOMIZED CONTROLLED TRIALS (DDW 2025) - " Advanced therapies evaluated were (in order of FDA approval) infliximab (ACT), adalimumab (ULTRA), golimumab (PURSUIT), vedolizumab (GEMINI), tofacitinib (OCTAVE), ustekinumab (UNIFI), ozanimod (TRUE NORTH), upadacitinib (U-ACHIEVE), etrasimod (ELEVATE UC), mirikizumab (LUCENT), risankizumab (INSPIRE; COMMAND), and guselkumab (QUASAR). This exploratory analysis helps to contextualize the efficacy of advanced therapies for UC assessed with different trial designs among different populations and highlights the persistent treatment gap that remains in UC. Further head-to-head studies would allow for further understanding of differences across treatments. Reference: 1."

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

An Open-label Study of Ozanimod in Moderate to Severe Ulcerative Colitis in Clinical Practice (clinicaltrials.gov) - P4 | N=139 | Terminated | Sponsor: Bristol-Myers Squibb | N=500 ➔ 139 | Active, not recruiting ➔ Terminated; Business objectives have changed.

Biomarker • Enrollment change • HEOR • Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

SYMPTOM RESPONSE TRAJECTORY ANALYSIS IDENTIFIES DISTINCT SUBPOPULATIONS IN MODERATE-TO-SEVERE ULCERATIVE COLITIS LINKED TO MAINTENANCE OUTCOMES: A PATIENT LEVEL POST-HOC ANALYSIS OF 2,378 PARTICIPANTS ACROSS 6 RCT'S WITH 8 ADVANCED THERAPIES (DDW 2025) - "Posthoc analysis of the SELECTION trial (filgotinib) demonstrated that analysis of daily PRO2 scores (stool frequency/rectal bleeding) as time-series data reveals discrete subpopulations...Methods In a cross-industry/academia collaboration, data from 2,378 UC participants from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment symptom response trajectories using group-based trajectory modeling (GBTM)...Symptom response trajectories may reflect underlying heterogeneity in individual disease biology in interaction with different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

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

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

Cytomegalovirus Isolated to a Colon Polyp in a Patient with Ulcerative Colitis on Ozanimod: A Case Report. (PubMed, Case Rep Gastroenterol) - "The patient successfully completed a 3-week course of valganciclovir. The unusual nature of this presentation suggests a clinically silent CMV reactivation or, alternatively, a primary CMV infection in our patient, with an unclear natural history and optimal management. This report emphasizes the importance of considering CMV in UC patients with unusual endoscopic findings and the need for multidisciplinary collaboration to optimize care."

Journal • Colonic Polyps • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Ulcerative Colitis

S1PR4-dependent effects of Etrasimod on primary human myeloid immune cell activation. (PubMed, Front Pharmacol) - "Primary human macrophages, plasmacytoid dendritic cells and neutrophils were pretreated with S1P, Etrasimod (S1PR1/4/5), Ozanimod (S1PR1/5), Siponimod (S1PR1/5), CYM 50308 (S1PR4 agonist) and CYM 50358 (S1PR4 antagonist), and then stimulated with Zymosan A, ODN 2336 and PMA, respectively. Regarding receptor dynamics, we show that Etrasimod induces internalization of S1PR4. Taken together, our data show that S1PR4 takes on an essential role in the regulation of various immunological functions, and that Etrasimod can act as a superagonist/functional antagonist of S1PR4."

Journal • CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis • CCL20 • CXCL5 • IFNA1 • S1PR1

A RARE CASE OF ACUTE ON CHRONIC PAIN IN SETTING OF LUMBAR SPINAL STENOSIS AND MULTIPLE SCLEROSIS (ASRA-SPRING 2025) - "Here, we present a case of lumbar spinal stenosis and associated radiculopathy in a patient with MS causing diagnostic difficulty CASE PRESENTATION A 47-year-old female with history of multiple sclerosis (diagnosed in 2003) on Ozanimod, L5-S1 spinal stenosis on cyclobenzaprine, tizanidine, and gabapentin, prior radiculopathy and myofascial pain - having received multiple trigger point injections with lidocaine over bilateral cervicothoracic paraspinals and prior TFESI (Transforaminal Lumbar Epidural Steroid Injections) in 2015, presented to the emergency department in 2024 with shooting pain starting at her right hip progressing down the back of her leg with associated numbness on the right ankle and foot...She was started on a multimodal pain regimen including oxycodone 5 mg, acetaminophen 975 mg, ibuprofen 800 mg, lidocaine patch, gabapentin 600 mg, cyclobenzaprine 10 mg, duloxetine 30 mg and hydromorphone for breakthrough pain...This case highlights the importance of..."

Clinical • CNS Disorders • Inflammation • Multiple Sclerosis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain

Evaluating Cognitive Outcomes in Multiple Sclerosis: Real-World Impact of Ozanimod on Processing Speed Using BICAMS. (PubMed, Neurol Ther) - "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."

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

INCREASED INTESTINAL S1P LEVELS AFTER SYSTEMIC AND INTESTINAL EPITHELIAL-SPECIFIC S1P LYASE INHIBITION DISRUPTED INTESTINAL BARRIER FUNCTION AND AGGRAVATED DSS-INDUCED COLITIS (DDW 2025) - "BACKGROUND: Sphingosine-1-phosphate (S1P) receptor agonists (e.g., ozanimod) desensitize migrating lymphocytes by irreversibly binding to S1P receptors (S1PR) and triggering proteasomal degradation... Thus, homeostatic intestinal S1P levels are critical for the regulation of both endothelial and IEC barrier function. Further investigation of the IEC-specific strategy using adaptive immune IBD models are required to investigate the translational value of SPL inhibition as a therapeutic target for human IBD."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • CD4 • CD8

Exploring Ozanimod's Role in Reducing Lung Inflammation in a Bacterial ARDS Model (IMMUNOLOGY 2025) - "Ozanimod also significantly reduced CD69 levels on lung lymphocytes. These results suggest that S1P1 targeting may offer therapeutic benefits in bacterial ARDS.Keywords: Animals Rodent; Infections Bacterial; Tissues Lung"

Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Influenza • Pneumococcal Infections • Pneumonia • Respiratory Diseases • CD69 • S1PR1

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) - "Circulating inflammatory markers of neutrophils and CPa9-HNE decreased with ozanimod use. These findings support the use of circulating neutrophils and CPa9-HNE, a measure of neutrophil activity, as pharmacodynamic markers for ozanimod treatment effect and potential disease markers in patients with UC."

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

ARTIFICIAL INTELLIGENCE ENDOSCOPIC VIDEO SCORING IS STRONGLY ASSOCIATED WITH QUALITY OF LIFE ASSESSMENTS IN A PIVOTAL PHASE 3 ULCERATIVE COLITIS TRIAL (DDW 2025) - P3 | "METHODS : Endoscopic videos were obtained from the pivotal phase 3 True North RCT of ozanimod (OZA) vs. placebo in UC (NCT02435992)...CONCLUSIONS : CDS values are strongly associated with standardized QoL measures in UC and can detect QoL differences unseen by conventional MES scoring. AI-enhanced grading of endoscopic activity that associates better with patient experiences may enable reliance on an objective measure as a single treatment endpoint in UC."

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

A Study on the Safety of Ozanimod Exposure in Pregnant Women and Their Offspring (clinicaltrials.gov) - P=N/A | N=1182 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jun 2031 ➔ Jun 2032 | Trial primary completion date: Jun 2031 ➔ Jun 2032

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

Leukocyte response modulation in hospitalized patients treated with ozanimod for an ongoing SARS-CoV-2 infection (IMMUNOLOGY 2025) - "While ozanimod appeared to impair the humoral response in unvaccinated individuals, it did not hinder the development of a strong anti-SARS-CoV-2 antibody response in vaccinated patients. These findings highlight the influence of ozanimod on key immune pathways during acute SARS-CoV-2 infection, offering insights into its potential therapeutic role."

Clinical • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CCL2 • CXCL8 • S1PR1

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