THE EFFECT OF INTRAVENOUS ADMINISTRATION OF A CHIMERIC ANTI-IGE ANTIBODY ON SERUM IGE LEVELS IN ATOPIC SUBJECTS - EFFICACY, SAFETY, AND PHARMACOKINETICS

CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human Ig E antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilon R1) on mast cells and basophils or low affinity IgE receptors (Fc epsi lon R2) on other cells. A phase 1 double-blind, placebo-controlled, si ngle dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was c onducted in 33 pollen-sensitive subjects who had raised levels of seru m IgE and received either intravenous CGP 51901 or placebo. The admini stration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression af ter 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of bas eline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newl y synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response aga inst CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of ato pic diseases.