Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria

de Latour, RP; Kulasekararaj, A; Dingli, D; Wilson, K; Wojciechowski, P; Hakimi, Z; Nazir, J; Czech, B; Hillmen, P; Szer, J

Author(s): de Latour, RP; Kulasekararaj, A; Dingli, D; Wilson, K; Wojciechowski, P; Hakimi, Z; Nazir, J; Czech, B; Hillmen, P; Szer, J;
Details: Publication Year 2025-08,Volume 115,Issue #2,Page 125-133
Journal Title: European Journal of Haematology
Publication Type: Research article
Abstract: BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired non-malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients. OBJECTIVE: This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab). METHODS: Respective pivotal studies provided patient-level trial data for pegcetacoplan (16-week PEGASUS [NCT03500549]) and published data for iptacopan (24-week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient-reported outcomes on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis. RESULTS: Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change-from-baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (-0.49 g/dL [-1.78, 0.80]); ARC (-34.41 × 10(9)/L [-90.02, 21.21]); LDH level (-115.16 U/L [-244.40, 14.01]); FACIT-Fatigue score (3.57 [-5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient-reported fatigue, providing similar point estimates and confidence intervals. CONCLUSION: This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient-reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease- and patient-related factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03500549.
Publisher: Wiley
Keywords: Adult; Aged; Female; Humans; Male; Middle Aged; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &; dosage/adverse effects; *Complement Inactivating Agents/therapeutic use/adverse effects/administration &; dosage; *Hemoglobinuria, Paroxysmal/drug therapy/diagnosis/blood; Treatment Outcome; Benzoates; Indoles; Piperidines; indirect treatment comparison; iptacopan; paroxysmal nocturnal haemoglobinuria; pegcetacoplan
Department(s): Haematology
Publisher's Version: https://doi.org/10.1111/ejh.14422
Open Access at Publisher's Site: https://doi.org/10.1111/ejh.14422
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-02 01:58:36

Last Modified: 2025-07-22 06:23:47