The complement pathway is an important and complex regulatory system, playing major roles in both adaptive and innate immunity, as well as the response to inflammation. However, as has become more apparent recently, activation of the complement system has also been implicated in the pathogenesis of many diseases. These diseases include rheumatoid arthritis, macular degeneration, lupus erythematosus, and importantly, immune involvement in cancer.
Currently, one approved product is available which targets the complement pathway, namely eculizimab (Alexion), for the orphan indication of PNH. An important distinction is that eculizimab is a monoclonal antibody (mAb) antagonist of the downstream C5 pathway. Given that complement proteins are relatively abundant in human serum, our mechanism-of-action of enzymatic depletion versus antagonism, as well as our upstream intervention in the complement cascade, is anticipated to provide a clinical advantage.
V.M. Holers. (2008) Immunological Reviews 223: 300-316. The spectrum of complement alternative pathway-mediated diseases.