Vedolizumab, a humanized mAb against the α4β7 integrin for the potential treatment of ulcerative colitis and Crohn's disease.

Abstract

Advances in immunology and genetics have identified new therapeutic targets to control inflammation and symptoms in patients with inflammatory bowel diseases (IBD). Despite the success of anti-TNF therapies in the treatment of IBD, a considerable proportion of patients are refractory to treatment, highlighting an unmet medical need for new therapies. Molecules that direct the trafficking of inflammatory cells, such as the α4β7 integrin, are attractive targets for new drug candidates. The α4β7 integrin is involved in lymphocyte recruitment to the normal and inflamed gut mucosa, and the lymphoid tissue. The pan-α4 integrin neutralizing mAb, natalizumab, is not gut-selective but has demonstrated efficacy in IBD. However, treatment was associated with the occurrence of progressive multifocal leukoencephalopathy, which has limited its use, especially in Europe. Vedolizumab (MNL-0002), Millennium Pharmaceutical's gut-specific, α4β7 integrin-neutralizing mAb, does not affect peripheral blood cell counts and appears to lack systemic effects. Data from phase II clinical trials of vedolizumab demonstrated efficacy with an attractive safety profile, especially in ulcerative colitis. Large phase III, multicenter trials in both ulcerative colitis and Crohn's disease will provide valuable data for the ongoing development of vedolizumab, which might evolve as a new anti-inflammatory treatment option for the management of therapy-refractory patients.