Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies
Abstract: Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)–experienced (APPLY-PNH; NCT04558918) and C5i-naive (APPOINT-PNH; NCT04820530) patients with paroxysmal nocturnal hemoglobinuria (PNH). In the AP...
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Elsevier
2025-04-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925000059 |
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| author | Antonio M. Risitano Carlos de Castro Bing Han Austin Kulasekararaj Jaroslaw P. Maciejewski Phillip Scheinberg Yasutaka Ueda Susan Vallow Georgina Bermann Marion Dahlke Rakesh Kumar Régis Peffault de Latour |
| author_facet | Antonio M. Risitano Carlos de Castro Bing Han Austin Kulasekararaj Jaroslaw P. Maciejewski Phillip Scheinberg Yasutaka Ueda Susan Vallow Georgina Bermann Marion Dahlke Rakesh Kumar Régis Peffault de Latour |
| author_sort | Antonio M. Risitano |
| collection | DOAJ |
| description | Abstract: Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)–experienced (APPLY-PNH; NCT04558918) and C5i-naive (APPOINT-PNH; NCT04820530) patients with paroxysmal nocturnal hemoglobinuria (PNH). In the APPLY-PNH and APPOINT-PNH trials, changes in fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue]) and health-related quality of life (HRQOL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) from baseline to day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales was evaluated using anchor-based thresholds, and correlations between FACIT-Fatigue scores, lactate dehydrogenase (LDH), and hemoglobin (Hb) levels were assessed. In APPLY-PNH (iptacopan, n = 62; C5i, n = 33), more patients in the iptacopan versus the C5i group reached the MWPC threshold for FACIT-Fatigue (51% vs 11%). More patients achieved MWPC on EORTC QLQ-C30 subscales in the iptacopan group (39%-49%) versus the C5i group (9%-20%). In APPOINT-PNH (N = 40), 56% achieved MWPC on the FACIT-Fatigue, and the proportion of patients who achieved MWPC on the EORTC QLQ-C30 ranged from 41% to 55%. In C5i-experienced patients, increased Hb levels correlated with improvement in FACIT-Fatigue scores (R = 0.48); in C5i-naive patients, increased Hb (R = 0.42) and decreased LDH (R = −0.53) (all P < .001) correlated with improved FACIT-Fatigue scores. C5i-experienced and -naive patients receiving iptacopan exhibited meaningful improvement in fatigue, HRQOL, and disease-related symptoms, which correlated with clinical improvement in hematologic markers of disease control. |
| format | Article |
| id | doaj-art-982c130c065348b58e86669ed9bbfe20 |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-982c130c065348b58e86669ed9bbfe202025-08-20T03:08:42ZengElsevierBlood Advances2473-95292025-04-01981816182610.1182/bloodadvances.2024014652Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studiesAntonio M. Risitano0Carlos de Castro1Bing Han2Austin Kulasekararaj3Jaroslaw P. Maciejewski4Phillip Scheinberg5Yasutaka Ueda6Susan Vallow7Georgina Bermann8Marion Dahlke9Rakesh Kumar10Régis Peffault de Latour11Hematology and BMT Unit, AORN Moscati, Avellino, Italy; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Medicine, Duke University School of Medicine, Durham, NCDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Haematological Medicine, King’s College Hospital NHS, London, United Kingdom; National Institute for Health and Care Research and Wellcome King’s Research Facility, London, United Kingdom; King’s College London, London, United KingdomDepartment of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHDivision of Hematology, Hospital A Beneficência Portuguesa, São Paulo, BrazilDepartment of Hematology, Osaka University Graduate School of Medicine, Suita, JapanNovartis Services Inc, East Hanover, NJ; Correspondence: Susan Vallow, Novartis Services Inc, 1 Health Plz, East Hanover, NJ 07936;Novartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandNovartis Healthcare Private Limited, Hyderabad, IndiaFrench Référence Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France; Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, FranceAbstract: Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)–experienced (APPLY-PNH; NCT04558918) and C5i-naive (APPOINT-PNH; NCT04820530) patients with paroxysmal nocturnal hemoglobinuria (PNH). In the APPLY-PNH and APPOINT-PNH trials, changes in fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue]) and health-related quality of life (HRQOL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) from baseline to day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales was evaluated using anchor-based thresholds, and correlations between FACIT-Fatigue scores, lactate dehydrogenase (LDH), and hemoglobin (Hb) levels were assessed. In APPLY-PNH (iptacopan, n = 62; C5i, n = 33), more patients in the iptacopan versus the C5i group reached the MWPC threshold for FACIT-Fatigue (51% vs 11%). More patients achieved MWPC on EORTC QLQ-C30 subscales in the iptacopan group (39%-49%) versus the C5i group (9%-20%). In APPOINT-PNH (N = 40), 56% achieved MWPC on the FACIT-Fatigue, and the proportion of patients who achieved MWPC on the EORTC QLQ-C30 ranged from 41% to 55%. In C5i-experienced patients, increased Hb levels correlated with improvement in FACIT-Fatigue scores (R = 0.48); in C5i-naive patients, increased Hb (R = 0.42) and decreased LDH (R = −0.53) (all P < .001) correlated with improved FACIT-Fatigue scores. C5i-experienced and -naive patients receiving iptacopan exhibited meaningful improvement in fatigue, HRQOL, and disease-related symptoms, which correlated with clinical improvement in hematologic markers of disease control.http://www.sciencedirect.com/science/article/pii/S2473952925000059 |
| spellingShingle | Antonio M. Risitano Carlos de Castro Bing Han Austin Kulasekararaj Jaroslaw P. Maciejewski Phillip Scheinberg Yasutaka Ueda Susan Vallow Georgina Bermann Marion Dahlke Rakesh Kumar Régis Peffault de Latour Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies Blood Advances |
| title | Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| title_full | Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| title_fullStr | Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| title_full_unstemmed | Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| title_short | Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| title_sort | patient reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925000059 |
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