Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48&#160;Weeks: 307 Open-Label Extension Study

Patriquin, CJ; Bogdanovic, A; Griffin, M; Kelly, RJ; Maciejewski, JP; Mulherin, B; Peffault de Latour, R; R&#246;th, A; Selvaratnam, V; Szer, J; Al-Adhami, M; Horneff, R; Tan, L; Yeh, M; Panse, J

Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48 Weeks: 307 Open-Label Extension Study

Author(s): Patriquin, CJ; Bogdanovic, A; Griffin, M; Kelly, RJ; Maciejewski, JP; Mulherin, B; Peffault de Latour, R; Röth, A; Selvaratnam, V; Szer, J; Al-Adhami, M; Horneff, R; Tan, L; Yeh, M; Panse, J;
Details: Publication Year 2024-05,Volume 41,Issue #5,Page 2050-2069
Journal Title: Advances in Therapy
Publication Type: Research article
Abstract: INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first targeted complement component 3 (C3) PNH therapy, was safe and efficacious in treatment-naive and pre-treated patients with PNH in five clinical trials. METHODS: The 307 open-label extension (OLE) study (NCT03531255) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week 48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin > 12 g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6 g/dL; female, ≥ 12 g/dL) were assessed as percentage of patients with data available and no transfusions 60 days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported. RESULTS: Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin > 12 g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred. CONCLUSION: Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03531255.
Publisher: Springer Nature
Keywords: Humans; *Hemoglobinuria, Paroxysmal/drug therapy; Male; Female; Adult; Middle Aged; Hemoglobins/analysis; Treatment Outcome; Aged; Clinical trial; Complement inhibitor; Eculizumab; FACIT-Fatigue; Hemoglobin; Open-label extension; Paroxysmal nocturnal hemoglobinuria (PNH); Pegcetacoplan; Thrombosis; Transfusion
Department(s): Clinical Haematology
Publisher's Version: https://doi.org/10.1007/s12325-024-02827-8
Open Access at Publisher's Site: https://doi.org/10.1007/s12325-024-02827-8
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-17 04:32:35

Last Modified: 2024-07-17 04:35:46