Advancing Landscape of Paroxysmal Nocturnal Hemoglobinuria Treatment

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic bone marrow failure condition characterized by complement-mediated hemolytic anemia and thrombosis. Since its initial clinical description in 1882, somatic mutations in PIG-A were discovered in the 1990s. With an improved understanding of PNH biology, a focused effort on complement inhibitors led to the discovery of eculizumab, a C5 inhibitor initially approved by the FDA in 2007. Terminal complement pathway inhibition reduced intravascular hemolysis, anemia, and thrombosis. Further advancements in drug development for PNH include improved pharmacokinetics with ravulizumab in 2018 and the introduction of proximal complement inhibitors such as pegcetacoplan (2021), iptacopan (2023), and danicopan (2024), and crovalimab (2024) to enhance patient outcomes. With these new proximal and distal complement inhibitors in the treatment landscape, it is timely for clinicians to review the evolving landscape of PNH treatments and patient selection