Alexion Complement Inhibitor shows efficacy in animal models of Rheumatoid Arthritis; Report published in Proceedings of the National Academy of Sciences.

Pharmaceuticals Inc. announced today that its proprietary complement inhibitor has been proved to be effective in two different animal models of rheumatoid arthritis.

In a paper entitled "Anti-C5 Monoclonal Antibody Therapy Prevents Collagen-Induced Arthritis and Ameliorates Established Disease," published today in the Proceedings of the National Academy of Sciences, Yi Wang, Ph.D., and his collaborators at Alexion demonstrated that prophylactic administration of an antibody that selectively inhibits the cleavage of a pivotal complement component, C5, into pro-inflammatory components, eliminates the incidence of arthritis. When the therapeutic antibody is administered after the onset of severe arthritis, Dr. Wang and his colleagues demonstrated that the inflammation is quickly and substantially ameliorated, clinical swelling is significantly reduced and spread of disease to additional joints is totally prevented. Importantly, placing a therapeutic road block in the inflammation cascade selectively at complement component C5 arrests the disease process, yet leaves the vital immunoprotective parts of the complement system entirely intact.

Complement proteins, a group of twenty proteins circulating in the blood, are critical components of the body's immune system. Under normal circumstances, certain of these proteins, together with antibodies and white blood cells, act beneficially to protect the body by removing pathogenic microorganisms and disease-causing immune complexes. However, any of a number of stimuli including antibodies, pathogenic microorganisms, injured tissue, normal tissue, proteases (inflammatory enzymes) and artificial surfaces can locally activate complement proteins to cause inflammation. Many clinical studies have demonstrated the presence of certain activated complement proteins in inflamed joints of patients with arthritis.

Rheumatoid arthritis is a crippling disease characterized by repeated inflammation of the joints and eventual joint destruction accompanied by severe pain, loss of movement and deformity. Rheumatoid arthritis affects more than 2.5 million Americans, with 100,000 new cases diagnosed every year.

Dr. Louis Matis, Vice President of Research -- Immunobiology, at Alexion states, "This study demonstrates that cleavage of complement component C5 is a critical step in both the initiation and progression of arthritis. By selectively blocking only this step with a specific therapeutic antibody, clinical disease can either be prevented or, if disease is already established, inflammation is substantially reduced. In contrast to anti-cytokine therapies, administration of our C5 inhibitor was quite effective at preventing any significant cellular infiltration even after clinical disease was already established. We have now completed the humanization of a high affinity monoclonal antibody called h5G1.1, which prevents the cleavage of human C5 into its pro-inflammatory complement products. Development of h5G1.1 will be targeted at rheumatoid arthritis, lupus nephritis, and selected other inflammatory diseases for which we have established substantial preclinical efficacy."

Alexion has filed numerous patent applications worldwide covering both novel compositions of matter directed at the inhibition of C5 cleavage and methods of treatment of various inflammatory diseases with proprietary complement inhibitors. In preclinical studies, C5 inhibition has been observed to be effective in diverse inflammatory targets including arthritis, lupus, stroke, myocardial infarction, and surgical trauma. Alexion is currently in discussions with several healthcare firms regarding joint development of certain of these proprietary compositions.

Leonard Bell, M.D. President and Chief Executive Officer of Alexion, said,"We are very encouraged by the apparent efficacy of our proprietary complement inhibitors in a variety of inflammatory disease targets where current treatments are either ineffective or nonexistant. Importantly, the efficacious therapeutic results demonstrated in these studies were obtained without observable toxicity or untoward effects in the treated subjects. At this point in its development, h5G1.1 holds promise as a more effective and less toxic disease-modifying antirheumatic drug (DMARD)."

Alexion Pharmaceuticals Inc., founded in 1992, is a private, research-based biopharmaceuticals company headquartered in New Haven, CT focused on developing novel immunoregulatory biotherapeutics targeting severe autoimmune and cardiovascular disorders and organ transplantation.

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