Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement

Abstract

Eculizumab, a humanized monoclonal antibody against C5 that inhibits terminal complement activation, showed activity in a preliminary 12-week open-label trial in a small cohort of patients with paroxysmal nocturnal hemoglohinuria (PNH). The present study examined whether chronic eculizumab therapy could reduce intravascular hemolysis, stabilize hemoglobin levels, reduce transfusion requirements, and improve quality of life in a double-blind, randomized, placebo-controlled, multi-center global Phase III trial. It has been found that eculizumab stabilized hemoglobin levels, decreased the need for transfusions, and improved quality of life in PNH patients via reduced intravascular hemolysis. Chronic eculizumab treatment appears to be a safe and effective therapy for PNH.

1 . A method to improve at least one aspect of the quality of life of a patient suffering from paroxysmal nocturnal hemoglobinuria, said method comprising administering to said patient in need thereof a an antibody that binds C5, wherein the antibody comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4. 
     
     
         2 . The method of  claim 1  wherein said quality of life is measured by a FACIT-Fatigue score. 
     
     
         3 . The method, of  claim 2  wherein the FACIT-Fatigue score increases by at least 3 points. 
     
     
         4 . The method of  claim 2  wherein the FACIT-Fatigue score increases by at least 4 points. 
     
     
         5 . The method of  claim 1  wherein said quality of life is measured by an EORTC QLQ-C30 score. 
     
     
         6 . The method of  claim 5  wherein said EORTC QLQ-C30 score improves by at least 10% of the pretreatment score. 
     
     
         7 . The method of  claim 5  wherein said aspect of the quality of life as measured by an EORTC QLQ-C30 score is selected from the group consisting of a) global health status, b) physical functioning, c) emotional functioning, d) cognitive functioning, e) role functioning, f) social functioning, g) fatigue, h) pain, i) dyspnea, j) appetite loss, and k) insomnia. 
     
     
         8 . The method of  claim 7  wherein said aspect of quality of life is fatigue. 
     
     
         9 - 16 . (canceled) 
     
     
         17 . The method of  claim 1  wherein said antibody or active antibody fragment is administered for at least 6 months. 
     
     
         18 . The method of  claim 1  wherein said patient has aplastic anemia or myelodysplastic syndrome. 
     
     
         19 . The method of  claim 1  wherein said patient is anemic. 
     
     
         20 . The method of  claim 19  wherein said patient remains anemic following treatment. 
     
     
         21 . The method of  claim 19  wherein said patient has a hemoglobin level less than i) 14 g/dL if a man or ii) 12 g/dL if a woman. 
     
     
         22 . The method of  claim 19  wherein said patient has a hemoglobin level less than i) 13 g/dL if a man or ii) 11 g/dL if a woman. 
     
     
         23 . The method of  claim 19  wherein said patient has a hemoglobin level less than i) 12 g/dL if a man or ii) 10 g/dL if a woman. 
     
     
         24 . The method of  claim 1  wherein said compound antibody inhibits intravascular hemolysis. 
     
     
         25 . The method of  claim 1  wherein said method results in a greater than 30% reduction in LDH in said patient. 
     
     
         26 . The method of  claim 24  wherein said patient is anemic and said patient remains anemic after said administration. 
     
     
         27 . A method of prolonging the health-adjusted life expectancy of a patient comprising administering to said patient in need thereof an antibody that binds C5, wherein the antibody comprises a heavy chain consisting of SEQ ID NO: 2 and a light chain consisting of SEQ ID NO: 4. 
     
     
         28 - 51 . (canceled)