Velsipity (etrasimod) / Everest Medicines, Pfizer - LARVOL DELTA

ENDEAVOUR-UC: An Observational Study of Etrasimod in Adult Patients With Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Pfizer | Trial primary completion date: May 2027 ➔ Oct 2027

Real-world evidence • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A narrative review on the frequency, pathophysiology and management of bowel urgency associated with ulcerative colitis. (PubMed, Best Pract Res Clin Gastroenterol) - "Evidence suggests that mesalazine and budesonide foam may help reduce BU. Among advanced therapies, vedolizumab and Janus kinase inhibitors have demonstrated early improvements in urgency, anti-interleukin-23 antibodies have also shown promising effects. Additionally, the novel S1P receptor modulator etrasimod has been associated with symptomatic relief...Despite these therapeutic options, the management of BU remains challenging. Further research and the development of targeted treatments are warranted to address this unmet clinical need."

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

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

Efficacy and Safety of Etrasimod in Elderly Patients With Ulcerative Colitis (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: Showa Inan General Hospital

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

Cost-Effectiveness Analysis of Etrasimod Compared With Biologic Therapies for the Treatment of Patients with Moderately-to-Severely Active Ulcerative Colitis in Spain. (PubMed, Pharmacoecon Open) - "In AT-naïve and AT-experienced patients, etrasimod is a dominant therapy (cost savings, greater effectiveness) compared with commonly used ATs."

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

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

A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for etrasimod (Frontiers) - "We identified 2,104 AE reports from 967 patients—a larger cohort than previously described. The most frequent AEs were drug ineffectiveness, condition aggravated, headache, and dizziness. Signals were concentrated in gastrointestinal, general, and nervous system disorders. Strong signals included ulcerative proctitis, increased faecal calprotectin, and macular oedema. Critically, our comparative analysis suggested a potentially distinct safety profile for etrasimod, such as a more favorable signal for lymphocyte count decreased compared to other S1P modulators."

Real-world • Ulcerative Colitis

ENDEAVOUR-UC: An Observational Study of Etrasimod in Adult Patients With Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2027 ➔ Jul 2028

Real-world evidence • Trial completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Exhibitor Product Theater - Discover VELSIPITY® (etrasimod): An Rx tablet treatment option from Pfizer (ACG 2025) - "These programs are independent of the ACG 2025 Annual Scientific Meeting and Postgraduate Course programs. No CME is provided for Exhibitor Product Theater presentations."

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

Demographics and Clinical Characteristics of Patients With Ulcerative Colitis Receiving First-Line Advanced Therapies Categorized in AGA Guidelines as Lower, Intermediate, and Higher Efficacy (ACG 2025) - "Patients were categorized into the higher (etrasimod, infliximab, ozanimod, upadacitinib, and vedolizumab), intermediate (golimumab, mirikizumab, tofacitinib, and ustekinumab), and lower (adalimumab) efficacy groups. In total, 3,833 and 2,719 patients were included from the IQVIA and Optum databases, respectively, with a substantial proportion of patients in the lower efficacy group (lower: 34.9% and 23.8%; intermediate: 8.8% and 12.3%; higher: 56.4% and 64.0%; Figure 1). Within the higher efficacy group in IQVIA and Optum databases, respectively, 59.5% and 61.7% received vedolizumab, 39.7% and 34.8% received infliximab, and < 1% and 3.5% received other treatments. Age was significantly associated with higher vs."

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

Early Symptomatic Improvement Associations With Week 12 Outcomes: E-Diary Results From the Etrasimod ELEVATE UC Clinical Program (ACG 2025) - P3 | "Among pts reporting symptomatic response by Day 7 (etrasimod 2 mg, N1 = 151; placebo, N1 = 60), pts treated with etrasimod vs placebo demonstrated significantly greater CR (47.7% vs 15.0%, adjusted difference [Δ] 33.9, p < 0.001), EI (54.3% vs 20.0%, Δ 35.7, p < 0.001), and EIHR (31.1% vs 6.7%, Δ 24.8, p < 0.001) rates at Wk 12 (Table). In pts who did not demonstrate symptomatic response by Day 7 (etrasimod 2 mg, N1 = 376; placebo, N1 = 200), those treated with etrasimod vs placebo achieved significantly greater rates of CR (18.9% vs 10.0%, Δ 8.7, p = 0.002), EI (27.7% vs 17.0%, Δ 10.5, p = 0.002), and EIHR (16.0% vs 7.5%, Δ 8.3, p = 0.002) at Wk 12 (Table). Similarly, Day 7 RB and SF responders and nonresponders treated with etrasimod vs placebo also demonstrated significantly greater rates of CR, EI and EIHR at Wk 12 (all p < 0.001; Table). Pts treated with etrasimod may experience rapid symptomatic improvements."

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

Adherence to STRIDE-II Treat-to-Target Guidelines in Recent FDA-Approved IBD Drug Trials: A Comparative Review (ACG 2025) - "It remains unclear to what extent pivotal trials leading to these approvals adhered to STRIDE-II targets. A structured review was conducted of Phase 3 clinical trials that supported FDA approval of the following agents between 2021 and 2025: mirikizumab (Omvoh), guselkumab (Tremfya), upadacitinib (Rinvoq), etrasimod (Velsipity), infliximab-dyyb (Zymfentra), and subcutaneous vedolizumab (Entyvio SC). All six trials included clinical remission and endoscopic healing as primary or co-primary endpoints, consistent with STRIDE-II recommendations. However, none of the pivotal trials included biomarker normalization or validated QoL instruments as formal endpoints. Mirikizumab's LUCENT trials uniquely evaluated bowel urgency as a patient-reported symptom, a symptomatic target identified in STRIDE-II."

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

Bowel Urgency Outcomes Are Associated With Clinical Outcomes, Health-Related Quality of Life and Biomarkers in the Etrasimod ELEVATE UC 52 Clinical Trial (ACG 2025) - P3 | "A larger proportion of patients with BU remission (73.6%) and CMI in BU (78.9%) at Wk 12 were naïve to biologic/Janus kinase inhibitors vs experienced. At Wk 12, significantly more patients with vs without BU remission met efficacy endpoints (odds ratio, OR [95% confidence interval, CI]: clinical remission 4.0 [2.3, 7.1]; endoscopic improvement 3.6 [2.1, 6.2]; both p < 0.0001) and had significantly greater improvement in HRQoL scores and lower fCAL (all p < 0.05; Table). A similar association was seen for CMI in BU at Wk 12 (OR [95% CI]: clinical remission 3.7 [2.1, 6.4]; endoscopic improvement 2.6 [1.6, 4.3]; both p < 0.001; Table) and for patients meeting BU outcomes at Wk 52. Bowel urgency outcomes were associated with improvements in clinical and endoscopic endpoints, HRQoL scores and reduced fCAL at Wks 12 and 52."

Biomarker • Clinical • Clinical data • HEOR • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of Etrasimod for Moderate to Severe Ulcerative Colitis: A Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Six studies involving 689 patients met inclusion criteria. Etrasimod significantly improved:Clinical remission (OR 4.73; 95% CI: 2.57–8.71),Clinical response (OR 3.81; 95% CI: 2.61–7.03),Endoscopic improvement (OR 6.06; 95% CI: 3.96–9.27),Histologic healing (OR 6.05; 95% CI: 2.70–13.54),Steroid-free clinical remission (OR 5.19; 95% CI: 2.94–9.15),Symptomatic remission (OR 3.67; 95% CI: 2.50–5.39). No significant increase in serious adverse events (OR 1.02; 95% CI: 0.55–1.88), anemia (OR 0.85; 95% CI: 0.44–1.65), or UC worsening (OR 0.85; 95% CI: 0.44–1.65) was observed. Etrasimod demonstrates consistent efficacy across multiple remission endpoints and maintains a favorable safety profile."

Retrospective data • Anemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Review of Reports of Hepatic Failure and Hepatitis to the FDA Adverse Events Reporting System (FAERS) From Inflammatory Bowel Disease (IBD) Pharmacotherapy (ACG 2025) - "Reports of ADRs of all FDA approved IBD therapies including azathioprine, mercaptopurine, methotrexate, tacrolimus, balsalazide, mesalamine, osalazine, sulfasalazine, adalimumab, certolizumab pegol, golimumab, infliximab, natalizumab, vedolizumab, guselkumab, mirikixumab, risankizumab, ustekinumab, tofacitinib, upadacitinib, etrasimod, and ozanimod were reviewed. Tables 1 and 2 below show a truncated list of the reviewed medications, portraying significant ROR in ADR related to hepatitis or hepatic failure.There were 218 reports of hepatitis, and 135 reports of hepatic failure identified in patients with CD and UC. Azathioprine (ROR 4.26), mercaptopurine (ROR 3.08), and methotrexate (ROR 2.58) showed significant ROR for hepatitis in CD. Mercaptopurine (ROR 3.34), tacrolimus (ROR 21.17), and infliximab (ROR 1.86) showed significant ROR for hepatic failure in CD."

Adverse events • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Liver Failure • Ulcerative Colitis • ROR1

An Update on a Multi-Center, Prospective, Non-Interventional Study of the Real-World Effectiveness of Etrasimod in Patients With Ulcerative Colitis (ENDEAVOUR-UC) Living in the United States (ACG 2025) - P | "As of April 2025, 30 sites have been selected, 23 are recruiting, and 25 patients are enrolled. Initial results on early-enrolled patients are expected in 2026, and final results in 2028. Principal investigators are diverse in geography and practice type to enhance patient diversity. ENDEAVOUR-UC will provide insights on early effectiveness and durability of etrasimod in a real-world setting, with PROs efficiently captured in real time via an innovative, specialized web-based application.Figure: Figure."

Clinical • Observational data • Real-world • Real-world effectiveness • Real-world evidence • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of Novel Biological Therapies in Ulcerative Colitis: A Systematic Review (ACG 2025) - "Databases including PubMed, EMBASE, and Cochrane Central were searched through April 2024 for randomized controlled trials (RCTs) investigating novel biologics in UC, such as etrasimod, mirikizumab, ozanimod, and vedolizumab SC. Fourteen RCTs met inclusion criteria (N=8,612). Mirikizumab demonstrated superior clinical remission rates at week 12 (RR 2.24, 95% CI 1.71–2.94) compared to placebo. Etrasimod significantly improved endoscopic scores (RR 1.96, 95% CI 1.43–2.68)."

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

Long-Term Efficacy of Etrasimod in Patients With Ulcerative Colitis: 2-Year Outcomes From the ELEVATE Open-Label Extension (ACG 2025) - P3 | "A total of 296 pts were included, with a mean (standard deviation) etrasimod exposure of 120.0 (50.3; range: 3.0–218.3) wks. Most pts (n = 252; 85.1%) received ≥ 52 wks and 207 (69.9%) received ≥ 104 wks of open-label treatment. For this analysis, treatment was ongoing in 186 (62.8%) pts, while 109 (36.8%) had discontinued; reasons for discontinuation included pt withdrawal (n = 38; 12.8%), adverse events (n = 38; 12.8%), and lack of efficacy (n = 20; 6.8%)."

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

Etrasimod Therapy in Ulcerative Colitis: An Unexpected Hematologic Finding in a Patient With Leukemic Mantle Cell Lymphoma (ACG 2025) - "He has several comorbidities including dyslipidemia, coronary artery disease with stents, metabolic syndrome and recurrent DVT treated with Xarelto. Conversely, blockade of the specific S1P receptor, S1PR1 can inhibit S1P signaling and potentially reduce tumor growth.4 Blockade of S1P1 signaling can lead to natural killer T cell activation leading to effective anti-tumor effect.5,6 The concurrence of MCL and UC and CD is uncommon but has been reported in the literature.7 Both chronic inflammation and chronic immunosuppression are known to increase the risk of lymphoma. Awareness of the mechanism of action of this class of drugs should stimulate future research for new applications of these important biologically active molecules.8Figure: TABLE 1Figure: Table 2 & 3"

Clinical • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • Mantle Cell Lymphoma • Metabolic Disorders • Ulcerative Colitis • S1PR1 • SPHK1

Beyond the Colon: Acute Hemolysis Associated With Etrasimod (ACG 2025) - "His UC treatment changed from tofacitinib to etrasimod 2 months prior...Hematology recommended 100mg prednisone daily which was started on day 7, with recovery of hemoglobin...This case aims to add to the literature and report a rare adverse advent of this new medication.Figure: Figure 1: Trend of hemolysis related labs. (LDH: lactate dehydrogenase)"

Anemia • Cardiovascular • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Inflammatory Bowel Disease • Musculoskeletal Pain • Ulcerative Colitis

Efficacy of Etrasimod as First-Line Advanced Treatment Following Failure of Aminosalicylates Only: Data From the ELEVATE UC 52 Phase 3 Clinical Trial (ACG 2025) - P3 | "In total, 45 and 29 patients receiving etrasimod and placebo, respectively, had prior 5-ASA failure only and 244 and 115 patients did not. At Weeks 12 and 52, among those who had failed prior 5-ASA only, significantly more patients receiving etrasimod vs placebo achieved clinical remission (Week 12, % difference [Δ]: 38.3%, p = 0.002; Week 52, Δ: 24.3%, p = 0.008; Week 52, Δ: 27.8%, p < 0.001)."

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

Restarting Etrasimod After Treatment Interruption Is Not Associated With Cardiovascular Events: Analysis From the ELEVATE UC Clinical Program (ACG 2025) - "In this analysis, 25/747 (3.3%) pts experienced a dose interruption; 17 completed ELEVATE UC 52 or ELEVATE UC 12 or were ongoing in the open-label extension at the data cut (January 31, 2022). Mean time to first dose interruption was 205.5 days (standard deviation: 165.6); mean duration of interruption was 22.4 (10.9) days. Of TEAEs that led to dose interruption (22/25), decreased lymphocyte count (n = 8/25) was the most common; no CV events led to dose interruptions."

Clinical • Cardiovascular • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Metabolic Disorders • Migraine • Respiratory Diseases • Ulcerative Colitis