Experience with pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria and suboptimal response to C5 inhibitor therapy

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematologic disorder whose pathogenesis is primarily driven by the formation of a cell clone (the PNH clone) lacking surface protective glycoproteins (CD55 and CD59), activation of the alternative complement pathway, and complement-mediated destruction of erythrocytes within blood vessels (intravascular hemolysis). This process underlies the main clinical manifestations of PNH – hemolytic anemia and thrombotic complications. The introduction of eculizumab, a C5 complement inhibitor, into clinical practice in 2007, which blocks the mechanism of intravascular hemolysis, revolutionized the course and prognosis of PNH. However, 30–45 % of patients continue to experience anemia and require replacement blood transfusions after 6 months or more of regular C5 inhibitor therapy. It has been established that the most common cause of a suboptimal treatment response is extravascular hemolysis, which is based on opsonization of PNH erythrocytes by C3b complement fragments followed by phagocytosis and degradation of these cells by macrophages in the liver and spleen.

To suppress the mechanism of extravascular hemolysis, inhibitors of the proximal complement pathway have been developed, including the C3 inhibitor pegcetacoplan, which was registered in Russia in 2023 under the trade name Empaveli. The drug inhibits the activity of C3 and C3b complement components and thereby blocks the entire complement activation cascade, providing suppression of both intravascular and extravascular hemolysis.

This article presents the first Russian experience of treating nine PNH patients with suboptimal response to C5 inhibitor therapy with pegcetacoplan. All nine patients demonstrated an average increase in hemoglobin levels of 25 g / L from baseline, achieving transfusion independence. The article also provides a detailed description of three clinical cases of particular interest.