Alternative Pathway Inhibitors for Orphan Indication

DESCRIPTION (provided by applicant): Paroxysmal Nocturnal Hemoglobinuria (PNH) is an orphan disease characterized by severe anemia, kidney and liver failure, and ultimately death, if left untreated. In 2007, FDA approved the first complement inhibitor, Eculizumab (Soliris(R)), for the treatment of PNH. Eculizumab binds to C5 and prevents C5 cleavage and the formation of C5b-9, a complement product responsible for erythrocyte hemolysis. This mechanism prevents intravascular hemolysis (IVH), reduces LDH release, and reduces the need for transfusion in patients; however, patients treated with Eculizumab still show signs of anemia and half of those who are treated continue to rely on blood transfusions for survival. Recent studies have shown an increased level of C3b accumulation on erythrocytes in Eculizumab-treated patients, causing a prominent phenomenon - extravascular hemolysis (EVH). Despite the staggering cost of the drug treatment per patient, results are only partially satisfactory due to the continuous