Abstract: Provided are methods for treating paroxysmal nocturnal hemoglobinuria in a subject who previously exhibited an inadequate response to an anti-C5 antibody therapy, by administering to the subject a therapeutically effective amount of an inhibitor of the alternative pathway of complement (e.g., one which inhibits a target upstream to complement 5 (C5), such as Factor D or complement 3 (C3)). Also provided herein are methods for treating PNH in a human subject, comprising administering to the subject a complement factor D inhibitor alone or in combination with an anti-C5 antibody, or antigen binding fragment thereof. In some embodiments, the patient previously exhibited an inadequate response to an anti-C5 antibody therapy.