Abstract
<b><i>Introduction:</i></b> Pegcetacoplan, the first approved proximal complement C3 inhibitor, showed superiority to eculizumab in improving hemoglobin levels and clinical outcomes in the phase 3 PEGASUS study in patients with paroxysmal nocturnal hemoglobinuria (PNH) and inadequate response to eculizumab. <b><i>Methods:</i></b> This analysis evaluates the efficacy and safety of pegcetacoplan for Japanese patients in PEGASUS, as they are known for different clinicopathologic features compared to non-Asian patients. Ten Japanese patients were enrolled to receive pegcetacoplan (<i>n</i> = 5) or eculizumab (<i>n</i> = 5) during the 16-week randomized controlled period. All patients received pegcetacoplan monotherapy during the open-label period until week 48. <b><i>Results:</i></b> Treatment with pegcetacoplan improved hemoglobin with a mean change from baseline of 2.4 g/dL at week 16, which was sustained through 48 weeks. Pegcetacoplan-treated Japanese patients experienced sustained improvements in key secondary efficacy endpoints, including freedom from transfusion, lactate dehydrogenase level, reticulocyte count, and FACIT-Fatigue score. The safety profile was consistent with previously reported data from pegcetacoplan studies. No events of hemolysis, meningococcal infection, or thrombosis were reported in the Japanese population and all Japanese patients remained on treatment throughout the study. <b><i>Conclusion:</i></b> These data suggest that Japanese patients with PNH can be effectively and safely managed with pegcetacoplan.