ontamalimab (TAK-647) / Takeda, Pfizer - LARVOL DELTA

Gut-directed therapeutics in inflammatory bowel disease. (PubMed, Curr Opin Gastroenterol) - "Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or in combination with currently available therapies. Future directions should focus on the development of tried-and-true modalities (mAbs, small molecules) as well as the microbiome and more innovative delivery systems."

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

Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins (PubMed, Korean J Gastroenterol) - "Etrolizumab (anti-β7) blocks leukocyte trafficking via α4β7 and cell adhesion via αEβ7 integrins. In addition, the introduction of subcutaneous vedolizumab showed similar efficacy and safety with improved patients' convenience. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG)."

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

Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis. (PubMed, Drug Saf) - "A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents."

Retrospective data • Review • CNS Disorders • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Multiple Sclerosis • Oncology • Primary Immunodeficiency • Rare Diseases • Solid Tumor

A Safety Extension Study of Ontamalimab in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA) (clinicaltrials.gov) - P3 | N=556 | Completed | Sponsor: Shire | Active, not recruiting ➔ Completed

Trial completion • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease. (PubMed, J Crohns Colitis) - "Ontamalimab 75 mg was effective with no safety concerns as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis."

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

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review. (PubMed, Pharmaceuticals (Basel)) - "Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy."

Journal • Review • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Promising phase II biologics for future Crohn's disease therapy. (PubMed, Expert Opin Investig Drugs) - "Among the most promising biologics are interleukin (IL)-23p19 inhibitors (guselkumab, mirikizumab, and brazikumab), IL-6 inhibitors, and anti-adhesion molecules (ontamalimab). In addition to efficacy, some of them provide reassuring safety profiles. Phase III trials need to confirm these results, especially on their long-term safety issues."

Journal • P2 data • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Differential effects of ontamalimab versus vedolizumab on immune cell trafficking in intestinal inflammation and IBD. (PubMed, J Crohns Colitis) - "Ontamalimab has unique and broader mechanisms of action compared to vedolizumab. However, this seems to be compensated by redundant cell trafficking circuits and leads to similar preclinical efficacy of anti-α4β7 and anti-MAdCAM-1 treatment. These results will be important for the interpretation of pending phase III data."

Immune cell • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

PREDICTIVE TRANSLATIONAL BLOOD BIOMARKER DYNAMICS OF SMALL MOLECULE α4β7 INHIBITION IN NONHUMAN PRIMATE (DDW 2023) - "Conclusion : Increases of circulating CD4+β7hi Tmem cells and CCR9 mRNA in NHP blood treated with MT-105 represent biomarker data that mimicked data previously shown in human studies (using vedolizumab, ontamalimab, or MORF-057). Our cell atlas also serves as a valuable resource for investigating the heterogeneity of immune cells and the biological role of α4β7 in NHPs and humans. Following this collection of biomarkers in patients will be important to understand the translation of these findings and what implications different degrees of inhibiting the pathway have on disease resolution."

Biomarker • Inflammatory Bowel Disease • PTPRC

The Underappreciated Role of Secretory IgA in IBD. (PubMed, Inflamm Bowel Dis) - "Intestinal B cell recruitment is critically dependent on integrin α4β7-MAdCAM-1 interactions, yet antibodies that target α4β7 (ie, vedolizumab), MAdCAM-1 (ie, ontamalimab), or both β7 integrins (α4β7 and αE [CD103] β7; etrolizumab) are in clinical use or development as IBD therapeutics. In both cases, de novo recruitment of IgA ASC to the intestinal lamina propria is compromised, leading to bacterial overgrowth, dysbiosis, and lethal colitis. Thus, despite the safe and effective use of anti-integrin antibodies in patients with IBD, much remains to be learned about their various cell targets."

Journal • Cholera • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL10 • ITGA4 • ITGAE

Review: emerging drug therapies in inflammatory bowel disease. (PubMed, Aliment Pharmacol Ther) - "Several new IBD drug therapies have positive efficacy and safety data in early clinical trials, and there are several drugs in the therapeutic pipeline. As more treatments for CD and UC are approved for clinical use, research to assess predictors of response to therapy and head-to-head trials is needed to inform providers on how to best position therapeutic options for patients with IBD."

Clinical • Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL23A

A Safety Extension Study of Ontamalimab in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA) (clinicaltrials.gov) - P3 | N=557 | Active, not recruiting | Sponsor: Shire | Recruiting ➔ Active, not recruiting

Enrollment closed • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety Study of Ontamalimab as Maintenance Treatment in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 307) (clinicaltrials.gov) - P3 | N=40 | Terminated | Sponsor: Shire | Completed ➔ Terminated; Sponsor decision to discontinue the SHP647 (ontamalimab) clinical trial development program for inflammatory bowel diseases (IBD) early.

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

A Safety Extension Study of Ontamalimab in Participants With Moderate to Severe Ulcerative Colitis or Crohn’s Disease (AIDA) (clinicaltrials.gov) - P3; N=451; Recruiting; Sponsor: Shire; N=3384 ➔ 451; Trial completion date: Jun 2025 ➔ Dec 2023; Trial primary completion date: Feb 2025 ➔ Dec 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Sphingosine 1-phosphate modulation and immune cell trafficking in inflammatory bowel disease. (PubMed, Nat Rev Gastroenterol Hepatol) - "The complex biological processes of leukocyte recruitment, activation, adhesion and migration have been targeted by various monoclonal antibodies (vedolizumab, etrolizumab, ontamalimab). This Review summarizes the critical mediators and mechanisms involved in immune cell trafficking in IBD and the available evidence for efficacy, safety and pharmacokinetics of S1P receptor modulators in IBD and other immune-mediated disorders. Further, it discusses potential future approaches to incorporate S1P modulators into the treatment of IBD."

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

Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn’s Disease: The OPERA II Study. (PubMed, Inflamm Bowel Dis) - P1, P2 | "Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks.ClinicalTrials.gov ID: NCT01298492."

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

Efficacy and Safety Study of Ontamalimab as Maintenance Treatment in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 307) (clinicaltrials.gov) - P3; N=40; Completed; Sponsor: Shire; Active, not recruiting ➔ Completed; Trial primary completion date: Nov 2021 ➔ Jun 2021

Clinical • Trial completion • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Psychometric Properties of the Ulcerative Colitis Electronic Diary (UC e-Diary) in Adult Patients with Moderate-to-Severe Ulcerative Colitis (ACG 2021) - P3 | " We employed data from 2 Phase 3, randomized, double-blind, placebo-controlled studies of ontamalimab vs placebo in patients with moderate-to-severe UC (NCT03259334 and NCT03259308) (N=657)... While rectal bleeding and urgency items exhibited ceiling effects at baseline, ceiling effects were not evident at the total score level. At week 12, four items (rectal bleeding, urgency, bowel movements, and diarrhea) demonstrated ceiling effects, with 30% reaching a score of 0. The factor analysis supported a unidimensional domain structure."

Clinical • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pain • Ulcerative Colitis

Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives. (PubMed, Clin Exp Gastroenterol) - "Natalizumab (anti-α4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α4β7) is approved for the treatment of ulcerative colitis (UC) and CD...Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α4β7 IgG2), PN-943 (orally administered and gut-restricted α4β7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α4), and ontamalimab (anti-MAdCAM-1 IgG)."

Journal • Review • CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Rare Diseases • Ulcerative Colitis • ITGA4

Anti-integrin drugs in clinical trials for inflammatory bowel disease (IBD): Insights into promising agents. (PubMed, Expert Opin Investig Drugs) - "This review summarizes efficacy and safety data from phase 1, 2 and 3 clinical trials on investigational drugs, including monoclonal antibodies (etrolizumab, abrilumab, ontamalimab) and oral small molecules (AJM300, PTG-100). Among the most exciting features of this class are the gut selectivity, the convenient subcutaneous and oral administrations and the reassuring safety profiles. Most of the new anti-integrins seem to improve outcomes in UC but not in CD, however these data are far from definitive and several pivotal trials are still under way."

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

FIGARO UC 303: An Efficacy and Safety Study of Ontamalimab as Maintenance Therapy in Participants With Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P3; N=366; Completed; Sponsor: Shire; Active, not recruiting ➔ Completed

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

FIGARO UC 301: Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P3; N=380; Terminated; Sponsor: Shire; Completed ➔ Terminated; Sponsor decision to discontinue the SHP647 (ontamalimab) clinical trial development program for inflammatory bowel diseases (IBD) early.

Clinical • Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

Long-term safety and efficacy of the anti-MAdCAM-1 monoclonal antibody ontamalimab (SHP647) for the treatment of ulcerative colitis: the open-label study TURANDOT II. (PubMed, J Crohns Colitis) - "Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy."

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

FIGARO UC 301: Efficacy and Safety Study of SHP647 as Induction Therapy in Participants With Moderate to Severe Ulcerative Colitis (clinicaltrials.gov) - P3; N=380; Completed; Sponsor: Shire; Active, not recruiting ➔ Completed

Clinical • Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

Efficacy and Safety Study of Ontamalimab as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 305) (clinicaltrials.gov) - P3; N=30; Terminated; Sponsor: Shire; Trial completion date: Jul 2020 ➔ Oct 2020

Clinical • Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease