Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.

de Castro, C.; Kelly, RJ.; Griffin, M.; Patriquin, CJ.; Mulherin, B.; Hochsmann, B.; Selvaratnam, V.; Wong, RSM.; Hillmen, P.; Horneff, R.; Uchendu, UO.; Zhang, Y.; Surova, E.; Szamosi, J.; de Latour, RP.

Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.

All Authors

de Castro, C.

Kelly, RJ.

Griffin, M.

Patriquin, CJ.

Mulherin, B.

Hochsmann, B.

Selvaratnam, V.

Wong, RSM.

Hillmen, P.

Horneff, R.

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LTHT Author

Kelly, Richard
Griffin, Morag

LTHT Department

Oncology
Haematology

Publication Date

2025

Item Type

Journal Article
Clinical Trial
Multicenter Study

Abstract

INTRODUCTION: Pegcetacoplan, the first C3 and C3b inhibitor for paroxysmal nocturnal hemoglobinuria (PNH), demonstrated efficacy and safety in C5 inhibitor-experienced and -naive patients in the phase 3 studies PEGASUS (NCT03500549) and PRINCE (NCT04085601), respectively. This integrated analysis of PEGASUS, PRINCE, and their subsequent open-label extension study (NCT03531255) evaluated pegcetacoplan long-term efficacy and safety. METHODS: Efficacy was assessed from pegcetacoplan initiation through 2.5 years (PRINCE) and 3 years (PEGASUS) by measuring hemoglobin, lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores. Transfusion avoidance and safety were assessed during pegcetacoplan monotherapy. Of 133 patients in PRINCE and PEGASUS, 114 enrolled in the extension. Most patients (PRINCE, 81.1%; PEGASUS, 75.0%) were transfusion dependent at trial entry and baseline hemoglobin was below normal. RESULTS: Pegcetacoplan markedly and rapidly (within 4 weeks) improved all efficacy measures, which stabilized close to (hemoglobin, FACIT-Fatigue) or within (LDH, ARC, indirect bilirubin) normal range for up to 3 years; annual transfusion avoidance rates were 79.5-86.4% in PRINCE and 71.2-79.2% in PEGASUS. No new safety concerns were identified over 3 years. Serious adverse events were reported in 73 (55.3%) patients, deemed pegcetacoplan related in 6 (4.5%) patients. Most injection site reactions were mild, and their incidence decreased over time. Five (3.8%) deaths occurred (none deemed pegcetacoplan related); 37 (28.0%) patients experienced clinically significant and laboratory-confirmed breakthrough hemolysis; 4 thrombotic events occurred in 3 (2.3%) patients; no meningitis cases were reported. CONCLUSION: Pegcetacoplan efficacy and safety was sustained for up to 3 years in patients with PNH, with or without prior C5 inhibitor treatment, verifying the long-term favorable clinical profile of this proximal complement inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov NCT03500549 (PEGASUS), NCT04085601 (PRINCE), and NCT03531255 (307 OLE).