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Introduction <p>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&#xa0;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.</p> Methods <p>Efficacy was assessed from pegcetacoplan initiation through 2.5&#xa0;years (PRINCE) and 3&#xa0;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.</p> Results <p>Pegcetacoplan markedly and rapidly (within 4&#xa0;weeks) improved all efficacy measures, which stabilized close to (hemoglobin, FACIT-Fatigue) or within (LDH, ARC, indirect bilirubin) normal range for up to 3&#xa0;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&#xa0;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.</p> Conclusion <p>Pegcetacoplan efficacy and safety was sustained for up to 3&#xa0;years in patients with PNH, with or without prior C5 inhibitor treatment, verifying the long-term favorable clinical profile of this proximal complement inhibitor.</p> Trial Registration <p>ClinicalTrials.gov NCT03500549 (PEGASUS), NCT04085601 (PRINCE), and NCT03531255 (307 OLE).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Carlos de Castro,
  • Richard J. Kelly,
  • Morag Griffin,
  • Christopher J. Patriquin,
  • Brian Mulherin,
  • Britta Höchsmann,
  • Veena Selvaratnam,
  • Raymond Siu Ming Wong,
  • Peter Hillmen,
  • Regina Horneff,
  • Uchendu O. Uchendu,
  • Yiwei Zhang,
  • Elena Surova,
  • Johan Szamosi,
  • Regis Peffault de Latour

摘要

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).