Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti‐C5 therapy

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.

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Publication Details

Journal
HemaSphere
Published
2026-05-29
DOI
https://doi.org/10.1002/hem3.70384
Primary Topic
Complement system in diseases
Type
article
Field-Weighted Citation Impact
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Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti‐C5 therapy

Michael Loschi, Tao Ding, Marion Dahlke, MN Yenerel et al.
HemaSphere
Complement system in diseases
article

Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti‐C5 therapy

Michael Loschi, Tao Ding, Marion Dahlke, MN Yenerel, Tomasz Lawniczek, David J. Araten, Rosario Notaro, Irina Murakhovskaya, DJ Kuter, Eloy Roman, Schubert, Eros Di Bona, Joan Beckman, Navin Mahajan, Luca Monaco, Vinod Pullarkat, Austin Kulasekararaj, Nicolas Blin, Régis P. de Latour, Ilene Weitz, Srinivas Tantravahi, Jun H. Jang, Richard J. Kelly, Flore S. de Fontbrune, Jens Panse, Anna Gaya, Hubert Schrezenmeier, Bhumika J. Patel, Antonio M. Risitano, Abhay Singh, Philippe Ferber, Alexander Röth
article en

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.

HemaSphereVol. 10(6)
Novartis (Switzerland) (CH), Prisma Health (US), Albert Einstein College of Medicine (US), City Of Hope National Medical Center (US), Cleveland Clinic (US), Montefiore Medical Center (US), Harvard University (US), Universität Ulm (DE), Université Paris Cité (FR), University of Utah (US), University of Minnesota System (US), Huntsman Cancer Institute (US), Hotel Dieu Hospital (CA), St James's University Hospital (GB), German Red Cross (DE), Samsung Medical Center (KR), Centre Hospitalier Universitaire de Nice (FR), Service de Santé des Armées (FR), NYU Langone Health (US), Massachusetts General Hospital (US), Istituto per lo Studio e la Prevenzione Oncologica (IT), Novartis (China) (CN), Integrated Oncology (United States) (US), Assistance Publique – Hôpitaux de Paris (FR), European Society for Blood and Marrow Transplantation (NL), Azienda Ospedaliera S.Giuseppe Moscati (IT), Hospital Clínic de Barcelona (ES), Azienda Ospedaliero-Universitaria Careggi (IT), USC Norris Comprehensive Cancer Center (US), Essen University Hospital (DE), Ospedale San Bassiano (IT), King's College Hospital (GB), West German Heart and Vascular Center Essen (DE), New York University (US), University of Duisburg-Essen (DE), Istanbul University (TR), University of Naples Federico II (IT), Technische Universität Dresden (DE), RWTH Aachen University (DE)
Novartis Pharmaceuticals Corporation
Good health and well-being
Openalex Percentile: Top 9%
Complement system in diseases
DOIOpen Access PDFOpenAlex
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