The use of iptacopan with anti-C5 has been successful, with complete control of residual hemolysis.34 As a monotherapy, most of the recent literature shows 10 breakthrough events that occurred in 136 patients (7%), of which 8 were associated with complement amplification events such as COVID-19, infections or pregnancy.12 While these events were generally not severe and managed successfully with RBC transfusions and—in one case—eculizumab, iptacopan inherently carries a higher risk of severe BTH because the drug achieves such high levels of PNH RBCs (90%+).34 The gene discussed is C5; the disease is infection.