Омализумаб

Treatment of atopic disease (asthma; rhinitis) (monoclonal antibody).

Additional amino acid sequences have been incorporated into the antibody so that a humanized product resulted that only differs by 5% nonhuman amino acid residues. In vitro, omalizumab has been shown to complex with free IgE, forming trimers consisting of a 2:1 complex of IgE to omalizumab or a 1:2 complex of IgE to omalizumab. In addition, larger complexes also are formed, consisting of a 3:3 ratio of each. Omalizumab does not bind to IgE already bound to mast cells and, therefore, does not cause the degranulation that might be expected from such interaction. Thus, omalizumab effectively neutralizes free IgE and, aside from the obvious decrease of available IgE, also causes the down-regulation of FcεRI receptors on the mast cell surface, resulting in a decrease of IgE bound to the mast cell.

The bioavailability after subcutaneous administration is 62%, with slow absorption resulting in peak serum levels in 7 to 8 days from a single dose. Steady-state plasma concentration is reached in 14 to 29 days with multiple dosing regimens. The elimination of omalizumab is not clearly understood; however, studies have determined that intact IgE is excreted via the bile and that omalizumab:IgE complexes are cleared faster than uncomplexed omalizumab and slower than free IgE. This means that over time, total IgE concentrations (free and complexed IgE) increase, because the complex is cleared more slowly. The metabolism of omalizumab is not known, and the clearance of the complex is similar to the liver elimination of another immunoglobulin, IgG. The reticuloendothelial system degrades IgG, and it is believed that the same process occurs for the omalizumab:IgE complex.

The clinical role for omalizumab is in the treatment of allergic asthma. It is approved for the treatment of adults and adolescents 12 years of age and older whose symptoms are not controlled with inhaled glucocorticoids and who have a positive skin test for airborne allergens.