Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti‐C5 therapy
HemaSphere, vol. 10, pp. e70384
Abstract
Abstract Patients with paroxysmal nocturnal hemoglobinuria (PNH) on anti‐C5 often experience extravascular hemolysis with anemia. Iptacopan, the first oral proximal complement inhibitor targeting factor B, has shown efficacy and safety in PNH patients. APPULSE‐PNH (NCT05630001), a phase 3b, single‑arm, open‐label trial, enrolled adult patients with PNH and hemoglobin ≥10 g/dL on stable anti‐C5 for ≥6 months. Patients switched to iptacopan monotherapy (200 mg twice daily; 24 weeks). Primary endpoint: mean hemoglobin change from baseline across four visits (Days 126–168). At baseline, 57.7% of patients had elevated absolute reticulocyte counts (ARCs; above ULN = 123 × 10 9 /L) and 50% had C3 deposition on red blood cells (RBCs) >10%, indicative of extravascular hemolysis. There was a statistically significant increase in hemoglobin during the trial; adjusted mean change from baseline (95% CI) was +2.0 g/dL (1.7–2.3) overall, and in patients with baseline hemoglobin <12 g/dL and ≥12 g/dL, +2.4 (2.0–2.7) and +1.4 (1.0–1.8), respectively. Patients maintained transfusion independence, 92.7% with hemoglobin ≥12 g/dL. Adjusted mean change from baseline (95% CI) in lactate dehydrogenase and ARC were −1.3% (−6.6 to 4.3) and −89.2 × 10 9 /L (−95.5 to −82.9), respectively. Mean (SD) proportion of C3d+ PNH RBCs, assessed by flow cytometry, decreased from 11.0% (8.6) to 0.2% (0.7) at Day 168. No patients had breakthrough hemolysis or major adverse vascular events. FACIT‐Fatigue and treatment satisfaction scores improved by Days 84 and 168. Safety showed consistency with previous iptacopan PNH trials. Iptacopan improved hematologic outcomes in PNH patients with hemoglobin ≥10 g/dL on anti‐C5, maintaining control of intravascular hemolysis and resolving extravascular hemolysis.
Authors 32
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Austin Gladston Kulasekararaj corresponding
King's College Hospital · National Institute for Health and Care Research · European Society for Blood and Marrow Transplantation · European Society for Blood and Marrow Transplantation
Affiliation as printed
King's College Hospital NHS London UK
National Institute for Health and Care Research and Wellcome King's Research Facility London UK
The Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (UK, Italy and the Netherlands) Barcelona Spain
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European Society for Blood and Marrow Transplantation · European Society for Blood and Marrow Transplantation
Affiliation as printed
French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Paris France
The Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (UK, Italy and the Netherlands) Barcelona Spain
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Affiliation as printed
Hospital Clínic of Barcelona Barcelona Spain
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University of Southern California · USC Norris Comprehensive Cancer Center
Affiliation as printed
USC Norris Cancer Center, Keck‐USC School of Medicine Los Angeles California USA
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Harvard University · Massachusetts General Hospital
Affiliation as printed
Harvard Medical School Boston Massachusetts USA
Massachusetts General Hospital Boston Massachusetts USA
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Affiliation as printed
Prisma Health Cancer Institute Greenville South Carolina USA
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New York University · NYU Langone Health
Affiliation as printed
NYU Grossman School of Medicine New York New York USA
NYU Langone Medical Center New York New York USA
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Affiliation as printed
Cleveland Clinic Cleveland Ohio USA
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Samsung Medical Center · Sungkyunkwan University
Affiliation as printed
Samsung Medical Centre, Sungkyunkwan University School of Medicine Seoul Republic of Korea
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St James's University Hospital
Affiliation as printed
St James's University Hospital Leeds UK
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Affiliation as printed
UOC Oncoematologia, AULSS7 Pedemontana Bassano del Grappa Vicenza Italy
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Université Côte d'Azur · Centre Hospitalier Universitaire de Nice
Affiliation as printed
Nice University Hospital, Cote d'Azur University Nice France
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City Of Hope National Medical Center · City of Hope
Affiliation as printed
City of Hope Medical Center Duarte California USA
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Affiliation as printed
Department of Hematology, Cellular Therapy and Medical Oncology Dresden University Medical School Dresden Germany
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Azienda Ospedaliero-Universitaria Careggi · Istituto per lo Studio e la Prevenzione Oncologica
Affiliation as printed
Azienda Ospedaliera Universitaria Careggi Florence Italy
Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO) Florence Italy
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Affiliation as printed
Istanbul University, Istanbul Faculty of Medicine Istanbul Turkey
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Affiliation as printed
University of Minnesota Minneapolis Minnesota USA
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Centre Hospitalier Universitaire de Nantes
Affiliation as printed
CHU Hotel Dieu Nantes France
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Albert Einstein College of Medicine · Montefiore Medical Center
Affiliation as printed
Albert Einstein College of Medicine/Montefiore Medical Center Bronx New York USA
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Jens Panse Aachen
RWTH Aachen University · Universitätsklinikum Aachen
Affiliation as printed
Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf Aachen Germany
University Hospital RWTH Aachen Aachen Germany
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Affiliation as printed
Lakes Research Miami Lakes Florida USA
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Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Hematology and Stem Cell Transplantation West German Cancer Centre, University Hospital Essen, University of Duisburg‐Essen Essen Germany
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Universität Ulm · German Red Cross
Affiliation as printed
Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden‐Württemberg‐Hessen Germany
Institute of Transfusion Medicine University of Ulm Ulm Germany
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Affiliation as printed
Huntsman Cancer Institute University of Utah Salt Lake City Utah USA
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Assistance Publique – Hôpitaux de Paris · Université Paris Cité · European Society for Blood and Marrow Transplantation · European Society for Blood and Marrow Transplantation
Affiliation as printed
Assistance Publique Hôpitaux de Paris, Université Paris Cité Paris France
French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Paris France
The Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (UK, Italy and the Netherlands) Barcelona Spain
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Affiliation as printed
Novartis Pharma AG Basel Switzerland
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Affiliation as printed
Novartis Pharma AG Basel Switzerland
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Affiliation as printed
China Novartis Institutes For Biomedical Research Co. Ltd Shanghai China
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Affiliation as printed
Novartis Pharma AG Basel Switzerland
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Affiliation as printed
Novartis Pharma AG Basel Switzerland
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Affiliation as printed
Novartis Pharma AG Basel Switzerland
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Antonio Maria Risitano corresponding
University of Naples Federico II · Azienda Ospedaliera S.Giuseppe Moscati · European Society for Blood and Marrow Transplantation · European Society for Blood and Marrow Transplantation
Affiliation as printed
AORN Moscati Avellino Italy
The Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (UK, Italy and the Netherlands) Barcelona Spain
University of Naples Federico II Naples Italy
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