Real‐world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria

Abstract

Pegcetacoplan significantly improves outcomes for patients with paroxysmal nocturnal hemoglobinuria (PNH) experiencing extravascular hemolysis (EVH) on eculizumab, leading to approval in 2021/2022 (USA/Europe). We report the first collaborative real‐world evidence on pegcetacoplan use in UK and France. A total of 48 patients were either currently receiving or previously received pegcetacoplan (2019–2023). A total of 12 patients had participated in the PEGASUS clinical trial, continuing treatment after trial completion. Five patients were on combination treatment of C5 inhibition and pegcetacoplan. Mean pegcetacoplan duration was 20.2 months. Indication for pegcetacoplan was EVH on C5 inhibitors (Eculizumab, n = 29, Ravulizumab n = 16, others n = 3) with 35/48 patients requiring blood transfusion within the previous 12 months. Mean hemoglobin and reticulocyte count at pegcetacoplan commencement and after 3 months: 91 g/L and 205 × 109/L and 115.8 g/L and 107 × 109/L, respectively, resulting in mean Hb change of 22.3 g/L. Mean LDH pre‐ and post‐pegcetacoplan was unchanged. Six patients have stopped pegcetacoplan. A total of 32 breakthrough hemolysis (BTH) events occurred in 13/48 patients. A total of 14 events were within clinical trials (reported separately). Six patients experienced 18 acute BTH events outside clinical trials, 7/18 associated with complement activating conditions. Successful clinical management included daily pegcetacoplan subcutaneously for 3 days or single eculizumab doses; these events are manageable with prompt intervention. Pegcetacoplan is effective for patients with PNH experiencing EVH. In this large patient cohort, treatment was well tolerated with improved hemoglobin and reticulocytes and maintained LDH control. Although BTH occurs, this is manageable by acute dose modification, with the majority of patients being maintained on pegcetacoplan.

Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin ≥10 g/dL) who had received eculizumab or were naive to complement inhibitors

“…The breakthrough hemolysis event was rated as not related to treatment and resolved without study discontinuation. Because the strong complement cascade inhibition of proximal complement inhibitors for PNH, including pegcetacoplan, such therapies result in a large, circulating clones of PNH red blood cells, a reflection of their efficacy; however, more PNH red blood cells are then susceptible to complement-mediated hemolysis [ 35 , 36 ]. Two recent reports, one with real-world data and one with clinical trial data, have provided evidence that the breakthrough hemolysis events in pegcetacoplan-treated patients with PNH can be managed by short-term intensive dosing of pegcetacoplan and, in some cases, the temporary addition of eculizumab [ 35 , 36 ].…”