In vitro activity: Firategrast (formerly known as SB-683699 or T-0047) is an orally available alpha4 beta1/alpha4 beta7 (α4β1/α4β7) integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS). This could decrease multiple sclerosis (MS) activity, but may compromise CNS immune surveillance. Firategrast treatment was associated with modest decreases in median CSF total, CD4, CD8 and CD19 lymphocyte counts. The generally small magnitude of decreases suggests that sufficient numbers of lymphocytes can access the subarachnoid space, preserving CNS immune surveillance.

Cell Assay: Firategrast is an orally bioavailable α4β1/α4β7 integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS). Median (n, range) CSF lymphocyte counts (cells/μl) at weeks 0, 24, 28 and 36 were: 5.3 (44, 0.3-70.2), 3.3 (31, 0.0-99.0), 3.0 (32, 0.0-58.2) and 3.5 (29, 0.0-274.8). CD4+, CD8+ T- and CD19+ B-lymphocyte counts followed a similar pattern. Minimal changes were observed for CD3-CD16+CD56+ natural killer cells. Median CD4 : CD8 ratios were: 2.9 (41, 1.1-10.9), 2.2 (29, 0.6-5.9), 3.8 (28, 1.6-9.0) and 3.8 (21, 2.1-9.4). Blood lymphocyte counts were elevated at weeks 4 and 24, consistent with the mechanism of firategrast, and returned to baseline when firategrast was discontinued. There were minimal changes in CD4 : CD8 ratios.