Alexion Pharmaceuticals, Inc. has announced research findings showing that its anti-C5 monoclonal antibody can be effectively delivered to the lungs to substantially block airway inflammation and hyperresponsiveness in preclinical models of acute severe allergic asthma.
The compound used in the research is a surrogate of eculizumab, Alexion's lead anti-complement antibody. The study shows that anti-C5 monoclonal antibodies, including eculizumab, can be aerosolized for therapeutic use.
The data were presented at the annual meeting of the American Association of Immunologists in Boston by Yi Wang, Ph.D., Senior Research Fellow at Alexion.
In the study, the anti-C5 complement antibody was aerosolized with a standard nebulizer, a device commonly used to deliver asthma medication.
A single dose was found to be effective in blocking the bronchial inflammation and hyperresponsiveness that provoke airway constriction and have been shown to result in shortness of breath, wheezing, chest tightness and other asthma symptoms in asthmatic patients.
Complement is a complex series of blood proteins that work in concert with antibodies. The complement cascade refers to the precise series of events which activate each component of the complement system.
The anti-C5 complement antibody inhibits C5 from producing its two inflammatory byproducts, C5a and C5b-9.
By blocking both the C5a and C5b-9 inflammatory mediators (as opposed to blocking only the C5a as reported by others), researchers prevented airway inflammation during 10 weeks of repeated administration.
The data also showed that combining the antibody with a corticosteroid was more effective than either therapy alone.
"These studies add further to our previously published results (J. Clinical Investigation, Vol. 155, June 2005) demonstrating the utility of complement inhibition in models of severe allergic asthma," said Stephen Squinto, Ph.D., Executive VP and Head of Research at Alexion.
"We are further encouraged by the results reported today that anti-C5 antibodies, including eculizumab, can be successfully aerosolized and effectively delivered to the lung to prevent the inflammation that occurs during severe acute allergic asthma."
"Anti-complement blockade directly in the lung appears to be synergistic with corticosteroid treatment and, therefore, may eventually offer a novel therapeutic approach for treatment of the most severe forms of allergic asthma that often do not respond to standard corticosteroid therapy."
The data also underscore the emergence of complement activation as a key factor in the development of allergic asthma symptoms.
"Complement activation in the lung may be a critical inflammatory mediator in the development of airway hyperresponsiveness in patients with allergic asthma," said Paul O'Bryne, M.D., EJ Moran Campbell Professor of Medicine, Chairman, Department of Medicine, Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University.
"The development of an aerosolized form of eculizumab may, therefore, provide an important new tool for the treatment of this disease."