Vedolizumab, sold under the brand name Entyvio, is a monoclonal antibody medication developed by Millennium Pharmaceuticals, Inc. for the treatment of ulcerative colitis and Crohns disease. It binds to integrin α4β7 (LPAM-1, lymphocyte Peyers patch adhesion molecule 1, a dimer of Integrin alpha-4 and Integrin beta-7). Blocking the α4β7 integrin results in gut-selective anti-inflammatory activity. Medical use
Ulcerative colitis and Crohns disease
Vedolizumab has been approved for use in adults with moderate to severe ulcerative colitis or Crohns disease having a poor response to tumor necrosis factor (TNF) blockers or corticosteroids, or for those who are steroid-dependent. Checkpoint inhibitor colitis
Vedolizumab may be used to treat steroid refractory checkpoint inhibitor induced colitis, if infliximab is ineffective or contraindicated. Clinical trials
Ulcerative colitis
Vedolizumab has been investigated in several studies in adult patients. and at least 6 have results reported|date=June 2020}} Patients with moderate to severe active disease in whom conventional therapy or TNF-alpha antagonists were ineffective or could not be tolerated received either vedolizumab or placebo. The main measure of effectiveness was the proportion of patients whose symptoms improved after six weeks of treatment. Vedolizumab was shown to be more effective than placebo: 47% (106 out of 225) of patients who received vedolizumab showed an improvement in symptoms, compared with 26% (38 out of 149) of patients who received placebo. The study also showed that vedolizumab maintained the effect up to 52 weeks more effectively than placebo.
Dr. Andrew Lazarovits, a postdoctoral fellow in the laboratory, discovered the murine homologue of MLN0002, chiefly published the original key papers, and up until the late 1990s, coordinated and led the studies for its development and application for Crohns disease and ulcerative colitis. Dr. Lynn Bairds group showed the antibody reacted with a single protein band of 63Kd, and Dr. Atul Bhans group showed that it stained tissue lymphocytes but did not react with non-lymphoid tissues. Although Act-1 had limited efficacy in its ability to prevent kidney rejection in a sub-human primate transplantation model, Dr. Lazarovits continued to investigate the activities of Act-1 when he returned to Canada to become the Director of Transplantation at the University of Western Ontario.It was later determined that the Act-1 monoclonal antibody reacted with an α4β7 integrin that was subsequently shown to interact with a gut-associated addressin, MadCAM. Early work with Dr. Bruce Yacyshyn showed differential expression in inflammatory bowel disease. Dr. Lazarovits isolated the antibody to produce the murine homologue MLN002 which he licensed with the Massachusetts General Hospital to Millennium Pharmaceuticals of Boston for further development. Scientists at LeukoSite realized the potential of this antibody to treat inflammatory bowel disease, and this company was eventually acquired by Millennium which took an exclusive license to the cell line from Massachusetts General Hospital. In vivo proof of concept ultimately led to the decision to humanize the antibody and move it into clinical trials as "Vedolizumab".