PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.
Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.
Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.
Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.
Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.
Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.
Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.
A version of this article appeared on Medscape.com.