Novel targeted C3 inhibitor pegcetacoplan for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening acquired blood disease characterized by chronic complement-mediated hemolysis and thrombosis. On May 14, 2021, the US FDA approved a new targeted C3 therapy Empaveli (pegcetacoplan), once called APL-2, for use in adult PNH. This review aims to review the pharmacological properties, clinical safety and efficacy of pegcetacoplan, and provides comprehensive drug information about pegcetacoplan. Pegcetacoplan is a pegylated peptide that targets the proximal complement protein C3. Pegcetacoplan plays a role in the complement cascade that controls C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis. Early pharmacokinetic and pharmacodynamic trials proved that pegcetacoplan had good tolerability and acceptable safety, while reducing complement activity. The pivotal phase III trial PEGASUS of PNH patients with a suboptimal response to eculizumab reported that pegcetacoplan improved hemoglobin levels better than eculizumab (p < 0.001). Compared with eculizumab, patients who received pegcetacoplan had a higher chance of not requiring a blood transfusion within 16 weeks (85% vs. 15%, p < 0.001). The safety of pegcetacoplan was similar to that of eculizumab. Adverse events such as injection site reactions and diarrhea occurred frequently following pegcetacoplan administration. The prescription recommended dosage is 1080 mg, subcutaneously infusion twice a week.