Oral complement factor D inhibitor danicopan for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by episodic hemolysis, with additional clinical manifestations including thrombosis and bone marrow failure. The US FDA approved a complement factor D inhibitor, danicopan (Voydeya™), previously known as ACH-4471, for the treatment of extravascular hemolysis in adults with PNH on March 29, 2024. The primary purpose of this review is to examine the clinical efficacy and safety of danicopan. We systematically searched for articles on PubMed, Web of Science, and three publishers Springer, Elsevier, Wiley up to May 6, 2024. Danicopan acts on the alternative pathway of the complement cascade, preferentially controlling C3 fragment-mediated extravascular hemolysis. Recommended dosage is 150 mg orally three times a day, which can be increased to 200 mg three times a day when necessary. Vaccination is required before administration to prevent infections by encapsulated bacteria. In a pivotal phase 3 trial ALPHA, danicopan significantly increased hemoglobin levels compared to placebo (P<0.0001), 60% of patients experienced an increase in hemoglobin levels of at least 2 g/dL, compared to none in the placebo group (adjusted difference of 47%; P<0.0001). Common adverse events during danicopan treatment include headache and upper respiratory tract infection.