amiselimod (MT 1303) / Mitsubishi Tanabe, Bausch Health - LARVOL DELTA

Mucosal improvement and histologic healing with amiselimod for active Ulcerative Colitis: a phase 2, randomised, placebo-controlled trial (ECCO-IBD 2025) - "As well, significantly more patients in Group A (15.0%) and Group B (15.9%) vs placebo (5.6%) had mucosal healing at Week 12 ( P =0.02 for both vs placebo).The most common haematologic adverse events with amiselimod (group A, group B) vs placebo were leucopenia (8.4%, 15.9% vs 0%), anaemia (5.6%, 3.7% vs 3.7%), and neutropenia (1.9%, 5.6% vs 0%). Conclusion Both 12-week dosing regimens of amiselimod for UC were superior to placebo for inducing mucosal improvement and histologic healing with a favourable safety profile."

Clinical • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

The Sphingosine 1-Phosphate Receptor Modulator Amiselimod is Efficacious for the Treatment of Active Ulcerative Colitis: Results from a Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial (AIBD 2024) - "Twelve weeks of treatment with amiselimod (both groups) was well tolerated and efficacious (statistically superior to placebo) as a potential treatment for induction of remission of UC."

Clinical • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Bausch Health Reports Promising R&D Trial Updates on Amiselimod and Scientific Data Presented at International Healthcare Conferences (ACCESSWIRE) - P2 | N=322 | NCT04857112 | Sponsor: Bausch Health Americas, Inc. | "Bausch Health shared positive late-breaking data from a global Phase 2 study evaluating Amiselimod for the treatment of patients with active, mild to moderate ulcerative colitis (UC) at Digestive Disease Week (DDW) 2024....In the primary endpoint measure - both doses of Amiselimod (0.2mg and 0.4mg daily) led to a significantly greater improvement in Modified Mayo Score (MMS) compared to a placebo group on Day 85. This score reflects disease activity, with a lower score indicating better outcomes. Patients taking Amiselimod experienced an average improvement of -2.3 points, compared to -1.6 points in the placebo group (p-score <0.01)...endoscopic improvement and clinical remission, after 12 weeks, a significantly higher proportion of patients receiving Amiselimod achieved endoscopic improvement (over 42%) compared to placebo (23%) with statistically significant difference (p-score <0.01)."

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

AMISELIMOD FOR THE TREATMENT OF ACTIVE ULCERATIVE COLITIS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL (DDW 2024) - No abstract available

Clinical • Late-breaking abstract • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Salix to Present Late-Breaking Data from Phase 2 Trial of Amiselimod in Active Ulcerative Colitis at Digestive Disease Week 2024 (Bausch Health Press Release) - "Bausch Health Companies Inc...announced that they will be presenting data from its Phase 2 trial evaluating Amiselimod as treatment for active ulcerative colitis (UC). The data will be presented at Digestive Disease Week (DDW) 2024 during the IMIBD Late Breakers and Innovations in IBD session on Sunday, May 19, 2024, in Washington, D.C."

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Bausch Health Announces Positive Topline Results From Global Phase 2 Study Evaluating Amiselimod (an S1P antagonist) to Treat Ulcerative Colitis (Bausch Health Press Release) - P2 | N=322 | NCT04857112 | Sponsor: Bausch Health Americas, Inc. | "Bausch Health Companies Inc...today announced positive topline results from the Company’s Phase 2 study evaluating Amiselimod, an investigative S1P antagonist, for the treatment of ulcerative colitis (UC)...Amiselimod met the primary and key secondary endpoints including clinical and endoscopic measures in the double-blind period of the study; the open-label extension up to 52 weeks is currently ongoing. Efficacy results were similar for both dose groups (0.2 mg QD and 0.4 mg QD)...The topline results for the key endpoints were as follows: The primary endpoint, mean change in modified Mayo Score at Day 85 (-2.3) versus placebo (-1.6), (p = 0.002); 32.4% of patients on Amiselimod achieved clinical remission, compared to 17.8% on placebo, (p=0.007)...Amiselimod was well-tolerated...The full data set from this trial will be available early next year."

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis (clinicaltrials.gov) - P2 | N=322 | Active, not recruiting | Sponsor: Bausch Health Americas, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2023 ➔ Sep 2024 | Trial primary completion date: Oct 2023 ➔ Sep 2024

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

Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. (PubMed, Front Immunol) - "Thus, S1P modulation by Etrasimod is more effective than S1P antagonism by Amiselimod, at the dose tested, in ameliorating NASH, likely due to the alteration of leukocyte trafficking and recruitment. Etrasimod treatment results in a substantial attenuation of liver injury and inflammation in murine NASH."

Journal • Preclinical • Hepatology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis • ITGAM • LGALS3

A Randomized, Double-Blind, Parallel Design Thorough QT Study With a Nested Crossover to Compare the Cardiac Safety of Amiselimod With Placebo and Positive Control in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "All adverse events were mild to moderate in severity, and no deaths occurred. Amiselimod did not have any clinically relevant effect on the QTcF interval."

Clinical • Journal

PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF AMISELIMOD, A SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATOR, IN HEALTHY SUBJECTS: RESULTS FROM A PHASE 1 STUDY (CCCongress 2023) - "The abbreviated amiselimod dosing titration regimen reached steady state within 14 days for the therapeutic 0.4 mg QD regimen and within 26 days for the supratherapeutic 0.8 mg QD regimen; expected decreases in ALCs were observed following amiselimod."

Clinical • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

EFFICACY AND SAFETY OF ADVANCED ORAL THERAPIES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2022) - "Patients were randomised to placebo (n=1685), a JAK inhibitor (tofacitinib, n=1879; peficitinib n=176; upadacitinib, n=732; TD-1473, n=31; SHR0320, n=123; filgotinib, n=1199; ritlecitinib, n=150; brepocitinib, n=152) or an S1P receptor modulator (ozanimod, n=928; etrasimod, n=214; amiselimod, n=40; and KRP203, n=17). JAK inhibitors and S1P receptor modulators are effective for inducing clinical and endoscopic remission in UC. Filgotinib, upadacitinib, ozanimod, and etrasimod are also associated with improved histological outcomes in UC. JAK inhibitors are effective for inducing clinical remission in CD but may not provide a benefit for maintenance of remission."

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

A Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability and Efficacy of Amiselimod in Patients with Moderate to Severe Active Crohn’s Disease. (PubMed, J Crohns Colitis) - "Amiselimod 0.4 mg for 12 weeks was not superior to placebo for the induction of clinical response (CDAI 100) in Crohn's disease. Treatment with amiselimod 0.4 mg was generally well tolerated and no new safety concerns related to amiselimod were reported in this study."

Clinical • Journal • P2 data • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Updates on efficacy and safety outcomes of new and emerging disease modifying therapies and stem cell therapy for Multiple Sclerosis: A review. (PubMed, Mult Scler Relat Disord) - "The development of new DMTs continues to progress quickly today, and it can be difficult for clinicians to remain up to date on the most recent advancements and new treatment options for their patients. In this comprehensive review, we provide an outline of current MS medications in the pipeline including emerging DMTs and stem cell therapy, as well as the unique characteristics of these medications, including their indications, pharmacokinetic effects, and the relevant advancements."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis

Competitive Binding of Ozanimod and Other Sphingosine 1-Phosphate Receptor Modulators at Receptor Subtypes 1 and 5. (PubMed, Front Pharmacol) - "S1P receptor modulators FTY720-p, siponimod, etrasimod, ponesimod, KRP-203-p, and amiselimod-p also completely displacing radiolabeled ozanimod; thus, on a macroscopic level, all bind to the same site. Since all the S1P modulators included in this study display similar receptor pharmacology and compete for binding at the same site, they can be considered interchangeable with one another. The choice of any one particular agent should therefore be made on the basis of overall therapeutic profile, and patients can be offered the opportunity to switch S1P medications without the potential concern of additive S1P pharmacology."

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

Bausch Health Companies Inc. Announces First-Quarter 2022 Results (Canada Newswire) - "Salix segment reported and organic revenues were $464 million for the first quarter of 2022, as compared to $472 million for the first quarter of 2021, a decrease of $8 million, or 2%. The decrease was primarily driven by lower volumes due to the loss of exclusivity of certain products, partially offset by increased sales of XIFAXAN® (rifaximin), TRULANCE® (plecanatide)...Select Company and Pipeline Highlights...To date, 83 patients have been enrolled in Phase 2 trial evaluating amiselimod (S1P modulator) for the treatment of mild to moderate ulcerative colitis."

Commercial • Enrollment status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

P029 Pharmacokinetic/Pharmacodynamic Analysis of Amiselimod, a Selective Sphingosine 1-Phosphate Receptor Modulator, in Healthy Subjects: Results From a Phase 1 Study. (PubMed, Am J Gastroenterol) - "The abbreviated amiselimod dosing titration regimen reached steady state within 14 days for the therapeutic 0.4 mg QD regimen and within 26 days for the supratherapeutic 0.8 mg QD regimen; expected decreases in ALCs were observed following amiselimod."

Clinical • Journal • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Pharmacokinetic/Pharmacodynamic Analysis of Amiselimod, a Selective Sphingosine 1-Phosphate Receptor Modulator, in Healthy Subjects: Results From a Phase 1 Study (AIBD 2021) - "The abbreviated amiselimod dosing titration regimen reached steady state within 14 days for the therapeutic 0.4 mg QD regimen and within 26 days for the supratherapeutic 0.8 mg QD regimen; expected decreases in ALCs were observed following amiselimod."

Clinical • P1 data • PK/PD data • Immunology • Inflammation • Inflammatory Bowel Disease

P029 Pharmacokinetic/Pharmacodynamic Analysis of Amiselimod, a Selective Sphingosine 1-Phosphate Receptor Modulator, in Healthy Subjects: Results From a Phase 1 Study. (PubMed, Am J Gastroenterol) - No abstract available

Clinical • Journal • P1 data • PK/PD data

Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis (clinicaltrials.gov) - P2; N=336; Recruiting; Sponsor: Bausch Health Americas, Inc.; Initiation date: May 2021 ➔ Sep 2021

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

Ministry of Food and Drug Safety approves 8 clinical trials including treatment for hemophilia A [Google translation] (Health Korea News) - "The Ministry of Food and Drug Safety recently (16-17) approved eight clinical trials, including a treatment for hemophilia A...Clinical trial consignment agency PSICROR Korea has been approved for a phase 2 clinical trial for 'amiselimod' (amiselimod, MT-1303) from Bausch Health. To evaluate the efficacy and safety of 'Amicellimod' in 21 patients with mild to moderate ulcerative colitis (UC). 13 hospitals, including Ewha Womans University Mokdong Hospital, are conducting the clinical trial."

New P2 trial • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Effects of Amiselimod in patients with mild to moderate Ulcerative Colitis. Az Amiselimod (MT-1303) vizsgálat az enyhe/középsúlyos fekélyes vastagbélgyulladásban (colitis ulcerosa) szenvedőknél. (clinicaltrialsregister.eu) - P2; N=336; Ongoing; Sponsor: Salix Pharmaceuticals, Inc.

Clinical • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis. (PubMed, Drugs) - "Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment...Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients...Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases."

Journal • Cardiovascular • CNS Disorders • Dermatology • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Leukopenia • Lupus • Macular Edema • Multiple Sclerosis • Novel Coronavirus Disease • Ophthalmology • Psoriasis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • Targeted Protein Degradation

Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis (clinicaltrials.gov) - P2; N=336; Recruiting; Sponsor: Bausch Health Americas, Inc.; Not yet recruiting ➔ Recruiting

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

Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis. (PubMed, CNS Drugs) - "In March 2019, a breakthrough in MS treatment was achieved with the FDA approval for the second S1PR modulator, siponimod (Mayzent), for both active secondary progressive MS and relapsing-remitting MS...Furthermore, ozanimod received FDA approval in March 2020 for treatment of relapsing forms of MS, followed by subsequent approvals from Health Canada and the European Commission. Other second-generation selective S1PR modulators that have been tested for MS, with statistically significant data from phase II and phase III clinical studies, include ponesimod (ACT-128800), ceralifimod (ONO-4641), and amiselimod (MT-1303). This review covers the available data about the mechanisms of action, pharmacodynamics and kinetics, efficacy, safety, and tolerability of the various S1PR modulators for patients with relapsing-remitting, secondary progressive, and, for fingolimod, primary progressive MS."

Journal • Review • Cardiovascular • CNS Disorders • Immunology • Multiple Sclerosis • Rare Diseases

Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis (clinicaltrials.gov) - P2; N=336; Not yet recruiting; Sponsor: Bausch Health Americas, Inc.

Clinical • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis