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  1. Home
  2. Pegcetacoplan Versus Eculizumab In Paroxysmal Nocturnal Hemoglobinuria.
  1. Home
  2. Pegcetacoplan Versus Eculizumab In Paroxysmal Nocturnal Hemoglobinuria.

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Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria.

Peter Hillmen1, Jeff Szer1, Ilene Weitz1

  • 1From the Department of Haematology, St. James's University Hospital, Leeds (P.H., M.G.), and Lisa Tan Pharma Consulting, Cambridge (L.T.) - both in the United Kingdom; the Department of Clinical Haematology, Peter MacCallum Cancer Center and Royal Melbourne Hospital, Melbourne, VIC, Australia (J.S.); Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC, Los Angeles (I.W.); the Department of Hematology, West German Cancer Center University Hospital Essen, University of Duisburg-Essen, Essen (A. Röth), the Institute of Transfusion Medicine, University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Ulm (B.H.), and the Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen (J.P.) - all in Germany; the Department of Hematology, NTT Medical Center Tokyo, Tokyo (K.U.), and the Department of Hematology and Oncology, Okayama University Hospital, Okayama (H.N.) - both in Japan; Centre d'Investigations Cliniques (J.-J.K.) and the French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria (R.P.T.), Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris; the Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC (C.C.); Apellis Pharmaceuticals, Waltham, MA (M.H., P.D., C.F., F.G., T.A.); and the Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy (A. Risitano).

The New England Journal of Medicine
|March 17, 2021

View abstract on PubMed

Summary
This summary is machine-generated.

Pegcetacoplan demonstrated superiority over eculizumab in improving hemoglobin levels for patients with paroxysmal nocturnal hemoglobinuria (PNH). This novel C3 inhibitor offers broader hemolysis control, addressing both intravascular and extravascular types of the disease.

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Area of Science:

  • Hematology
  • Immunology
  • Pharmacology

Background:

  • Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder causing chronic complement-mediated hemolysis.
  • Current C5 inhibition effectively manages intravascular hemolysis but not extravascular hemolysis in PNH.
  • Pegcetacoplan, a C3 inhibitor, presents a potential therapeutic strategy for both intravascular and extravascular hemolysis.

Purpose of the Study:

  • To evaluate the efficacy and safety of pegcetacoplan compared to eculizumab in adults with PNH.
  • To assess pegcetacoplan's effectiveness in patients with suboptimal hemoglobin levels despite eculizumab therapy.
  • To determine pegcetacoplan's impact on hemolysis markers, transfusion requirements, and quality of life.

Main Methods:

  • A Phase 3, open-label, controlled trial involving adult PNH patients with hemoglobin <10.5 g/dL on eculizumab.
  • A 4-week run-in of pegcetacoplan plus eculizumab, followed by randomization to pegcetacoplan monotherapy (41 patients) or eculizumab (39 patients).
  • Primary endpoint: Mean change in hemoglobin from baseline to week 16; secondary endpoints included hemolysis markers and safety.
  • Main Results:

    • Pegcetacoplan showed superiority to eculizumab in mean hemoglobin change (3.84 g/dL difference, P<0.001).
    • Significantly more patients on pegcetacoplan avoided transfusions (85% vs. 15%).
    • Pegcetacoplan demonstrated noninferiority in reticulocyte count change but not LDH; fatigue scores improved.

    Conclusions:

    • Pegcetacoplan is superior to eculizumab in improving hemoglobin and clinical outcomes for PNH patients.
    • The C3 inhibitor pegcetacoplan provides comprehensive hemolysis control, targeting both intravascular and extravascular components.
    • Pegcetacoplan represents a significant advancement in PNH management, offering broader therapeutic benefits.