Journal article
Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia
Blood, Vol.145(4), pp.397-408
01/23/2025
DOI: 10.1182/blood.2023022549
PMID: 39486046
Abstract
Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in two cohorts, one for patients with CAD and the other wAIHA. In each cohort, patients were randomly assigned to receive 270 or 360 mg/day pegcetacoplan for up to 48 weeks. Safety endpoints included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy endpoints included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Thirteen (100%) and 10 out of 11 (91%) patients with CAD and wAIHA respectively experienced at least 1 TEAE. Ten patients had at least 1 serious adverse event; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90 to 3.00) and 1.7 g/dL (‑1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective in patients with CAD and wAIHA. Registered at www.clinicaltrials.gov (NCT03226678).Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in two cohorts, one for patients with CAD and the other wAIHA. In each cohort, patients were randomly assigned to receive 270 or 360 mg/day pegcetacoplan for up to 48 weeks. Safety endpoints included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy endpoints included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Thirteen (100%) and 10 out of 11 (91%) patients with CAD and wAIHA respectively experienced at least 1 TEAE. Ten patients had at least 1 serious adverse event; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90 to 3.00) and 1.7 g/dL (‑1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective in patients with CAD and wAIHA. Registered at www.clinicaltrials.gov (NCT03226678).
Details
- Title: Subtitle
- Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia
- Creators
- Eloy RomanBruno Fattizzo - Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMerrill Kingman ShumWahid T Hanna - University of Tennessee Medical CenterSteven R Lentz - University of IowaSergio Schusterschitz S AraujoMohammed Al-Adhami - Apellis PharmaceuticalsFederico V Grossi - Apellis PharmaceuticalsMorie A Gertz - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.145(4), pp.397-408
- Publisher
- ELSEVIER
- DOI
- 10.1182/blood.2023022549
- PMID
- 39486046
- ISSN
- 1528-0020
- eISSN
- 1528-0020
- Grant note
- SobiApellis Pharmaceuticals
Medical writing support was provided by Catherine Hoare (Bioscript Medical Ltd, Macclesfield, United Kingdom), funded by Sobi and Apellis Pharmaceuticals. Apellis and Sobi reviewed and provided feedback on the manuscript. The PLAUDIT study (ClinicalTrials.gov identifier: NCT03226678) was sponsored by Apellis Pharmaceuticals.
- Language
- English
- Electronic publication date
- 11/01/2024
- Date published
- 01/23/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984740951302771
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