Danicopan add-on therapy for extravascular hemolysis in a patient with paroxysmal nocturnal hemoglobinuria receiving ravulizumab

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis. Although C5 inhibitors effectively control intravascular hemolysis, some patients develop clinically significant extravascular hemolysis (EVH) because of upstream C3 deposition. A 56-year-old woman was diagnosed with PNH in 2019 and managed with intermittent transfusions. In October 2024, she developed progressive renal dysfunction; the PNH clone size was 95.72%. Ravulizumab was initiated in March 2025. Although the lactate dehydrogenase (LDH) level normalized after ravulizumab initiation, her hemoglobin (Hb) level remained below 10 g/dL, with marked reticulocytosis and continued transfusion requirements after more than 6 months of treatment. Danicopan, a factor D inhibitor, was added in November 2025. Subsequently, her Hb level exceeded 10 g/dL, reticulocyte counts gradually decreased, and transfusion dependence declined. This case demonstrates that adding danicopan to ravulizumab can reduce residual EVH and improve anemia in patients with PNH receiving C5 inhibitor therapy.