Anti-MAdCAM Antibodies Effective for Ulcerative Colitis in Phase II Trial

Lymphocytes that mediate inflammation in inflammatory bowel disease move from capillaries into inflamed tissue via adhesion molecules. Mucosal addressin cell adhesion molecule (MAdCAM) is present on endothelial surfaces and lymphoid tissue of the intestine. Gut homing T lymphocytes carry the α4β7 integrin on their surface, and binding of this integrin to MAdCAM allows lymphocyte migration. Vedolizumab binds to α4β7 integrin to block adhesion. The α4β7 integrin — MAdCAM interaction can also be blocked by antibodies to MAdCAM.

PF-00547659 is a human monoclonal antibody to MAdCAM that is given subcutaneously. In the current industry-funded phase II trial, researchers assessed the safety and efficacy of PF-00547659 in treating moderate-to-severe ulcerative colitis. They randomized approximately 350 patients to receive one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, and 225 mg) or placebo every 4 weeks for 12 weeks. The primary endpoint was remission, defined as a predetermined reduction in symptom and endoscopic scores.

The most effective doses were the intermediate doses of 22.5 and 75 mg, with differences in remission rates between drug and placebo of 13% and 12%, respectively. Mucosal healing was greatest with the 22.5-mg dose; the total percentage reduction in the endoscopic score was 24% more than with placebo. Total percentage decreases in fecal calprotectin concentrations were 57% to 58% with these two doses.