Table 1.
Anti-trafficking agents used in the clinic or still in development with details on their specific target, mode of action and preclinical and clinical efficacy.
| Target | Origin | Drug | Mode of action | Preclinical Data | Clinical Data | Observed effects | |||
|---|---|---|---|---|---|---|---|---|---|
| Model | Effective? | Disease | Administration | Primary endpoint(s) met? | |||||
| ICAM-1 | Endothelium | Alicaforsen | Anti-sense oligonucleotide | DSS colitis mouse model (13) | Yes | CD (Phase II) (16) | IV | No | Steroid withdrawal |
| CD (Phase II) (17) | IV | No | Steroid withdrawal | ||||||
| CD (Phase II) (18) | IV | No | N/A | ||||||
| UC (20) | Enema | Yes | Clinical response | ||||||
| Pouchitis (NCT02525523) | Enema | Not yet published | Reduced stool frequency | ||||||
| MAdCAM-1 | Endothelium | Ontamalimab | Monoclonal antibody | Adoptive T cell transfer colitis mouse model (35,36) | Yes | UC (Phase I) (37) | IV/SC | No | Changes in biomarkers compared to baseline |
| UC (Phase II) (38) | SC | Yes | Clinical remission | ||||||
| CD (Phase II) (39,40) | SC | No | Clinical remission in patients with higher endoscopic activity | ||||||
| UC and CD (Phase III) |
SC | Discontinued | |||||||
| CCR9 | Lymphocytes | Vercirnon | Small molecule antagonist | TNFΔARE ileitis mouse model (62) | Yes | CD (Phase II) (64) | PO | Yes | Clinical response, remission and steroid-free remission |
| CD (Phase III) (65) | PO | No | N/A | ||||||
| CXCL10 | Epithelium | Eldelumab | Monoclonal antibody | IL-10-/- and piroxicam colitis mouse model (74) | Yes | UC (Phase II) (78) | IV | No | Improvement of IBDQ score |
| DSS colitis mouse model (75) | Yes | UC (Phase II) (80) | IV | No | N/A | ||||
| IL-10-/- colitis mouse model (76) | Yes | CD (Phase II) (79) | IV | No | Numerically higher remission and response rates | ||||
| Smad7 | Epithelium | Mongersen | Anti-sense oligonucleotide | TNBS and oxazolone colitis mouse model (86) | Yes | CD (Phase II) (87) | PO | Yes | Clinical remission and response |
| CD (Phase III) (88) | PO | No | N/A | ||||||
| α4 integrin | Lymphocytes | Natalizumab | Monoclonal antibody | Cotton-top tamarin colitis model (103) | Yes | CD (24) | IV | Yes | Clinical remission and response |
| CD (25) | IV | Yes | Clinical remission and response | ||||||
| CD (Phase III) (26) | IV | Yes | Clinical response | ||||||
| CD (27) | IV | Yes | Clinical response | ||||||
| AJM300 | Small molecule antagonist | Adoptive T cell transfer colitis mouse model (107) | Yes | UC (Phase II) (109) | PO | Yes | Clinical remission and mucosal healing | ||
| α4β7 integrin | Lymphocytes | Vedolizumab | Monoclonal antibody | Cotton-top tamarin colitis model (96) |
Yes | UC (Phase III) (94) | IV | Yes | Clinical response, remission and mucosal healing |
| CD (Phase III) (97) | IV | Yes | Clinical response, remission and steroid-free remission | ||||||
| Abrilumab | Monoclonal antibody | N/A | UC (Phase II) (104) | SC | Yes | Clinical response, remission and mucosal healing | |||
| UC (Phase II) (105) | SC | Yes | Numerically higher remission, response and mucosal healing rates | ||||||
| β7 integrin | Lymphocytes | Etrolizumab | Monoclonal antibody | Adoptive T cell transfer colitis mouse model (123) | Yes | UC (Phase II) (110) | SC | Yes | Clinical remission |
| UC (Phase III) (124, 125, 127) |
SC | Yes/No | Clinical response and endoscopic improvement | ||||||
| CD (Phase III) | SC | Ongoing | |||||||
| S1PR | Lymphocytes | Ozanimod (S1PR1/5) | Small molecule agonist | TNBS colitis rat model and adoptive T cell transfer colitis mouse model (139) | Yes | UC (Phase II) (140) | PO | Yes | Clinical response and mucosal healing |
| UC (Phase III) (141, 142) |
PO | Yes | Clinical remission, response and mucosal healing | ||||||
| Etrasimod (S1PR1/4/5) | Small molecule agonist | Adoptive T cell transfer colitis mouse model (143) | Yes | UC (Phase II) (144) | PO | Yes | Clinical remission, response and histological improvement | ||
| Amiselimod (S1PR1) | Small molecule agonist | Adoptive T cell transfer colitis mouse model (146) | Yes | CD (145) | PO | No | Reduced lymphocyte counts | ||
IV, intravenous; SC, subcutaneous; PO, per os; UC, ulcerative colitis; CD, Crohn's disease; N/A, not available.