Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired blood disorder characterized by chronic destruction of red blood cells (hemolytic anemia) and blood clots (thrombosis).1 PNH can occur at any age, although it is most often diagnosed in young adulthood. the only cure for paroxysmal nocturnal hemoglobinuria (PNH) is an allogeneic hematopoietic stem cell transplantation.2 Stem cell transplantation is associated with high mortality and it is reserved for severe cases of PNH with aplastic anemia or transformation to leukemia, both of which are life-threatening complications.

Other treatment strategies include complement mediators that inhibit components of the complement system. Several monoclonal antibodies (ie, eculizumab, ravulizumab, crovalimab) that target the C5 complement component have been approved for treatment of PNH by the US Food and Drug Administration (FDA).3,4

A monoclonal antibody that inhibits C3, pegcetacoplan, has also been approved for treatment of PNH. Pegcetacoplan is a C3 inhibitor that is administered subcutaneously, twice weekly, and is capable of blocking both intravascular and extravascular hemolysis.5

Iptacopan, an oral inhibitor of factor B (a component of the alternative complement pathway) was approved by the FDA in 2023. It is indicated as monotherapy for PNH.6

Danicopan, a selective inhibitor of complement factor D, was approved by the FDA in 2024 for patients who experience clinically significant extravascular hemolysis, as an add-on to C5 inhibitor therapy (eg, eculizumab, ravulizumab).7

Additional treatment strategies are focused on managing the symptoms and complications of PNH. Depending on the anemia symptoms they experience, patients with PNH may receive supportive treatments, such as blood transfusion, iron replacement therapy, growth factors, and erythropoeitin. Steroids may also be used only for short-term use in symptomatic extravascular hemolysis. 8,9 Treatment with anticoagulants, including heparin and coumarin derivatives, may reduce the risk of thrombosis.1 Supplementation with folate, iron, and vitamin B12 can be used to support increased erythropoiesis in the bone marrow.