Real-world effectiveness of pegcetacoplan in individuals with paroxysmal nocturnal haemoglobinuria and suboptimal response to C5 inhibitors

Background Paroxysmal nocturnal haemoglobinuria (PNH) is characterised by complement-mediated haemolysis. Pegcetacoplan (PEG), a proximal complement inhibitor, offers alternative treatment for patients with suboptimal responses to C5 inhibitors (C5i). Objective To evaluate the real-world effectiveness and safety of PEG in PNH patients from Central and Eastern Europe (CEE) not responding optimally to C5i therapy. Design A multicentre, retrospective, observational cohort study. Methods This retrospective study analysed 26 adult patients who were switched to PEG therapy due to persistent anaemia despite C5i therapy. The patient inclusion period covered January 2023 to January 2025; data collection was conducted in February 2025, and the median treatment duration with PEG was 11.8 months. Key outcomes included haemoglobin levels, transfusion independence, and management of breakthrough haemolysis (BTH). Results PEG therapy resulted in a mean haemoglobin increase of 3.24 g/dL, normalisation of reticulocytosis and bilirubinaemia, and transfusion independence in 76.9% of patients. BTH events were effectively managed with dose adjustments or additional C5i, with no treatment discontinuations. Conclusion PEG demonstrates high efficacy in improving haemolysis control and clinical outcomes in PNH patients presenting with anaemia despite C5i therapy, aligning with PEGASUS trial findings and highlighting effective BTH management strategies.