Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.

Peffault de Latour, R.; Griffin, M.; Kelly, RJ.; Szer, J.; de Castro, C.; Horneff, R.; Tan, L.; Yeh, M.; Panse, J.

Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.

All Authors

Peffault de Latour, R.

Griffin, M.

Kelly, RJ.

Szer, J.

de Castro, C.

Horneff, R.

Tan, L.

Yeh, M.

Panse, J.

LTHT Author

Griffin, Morag
Kelly, Richard

LTHT Department

Haematology

Publication Date

2024

Item Type

Journal Article
Clinical Trial, Phase III
Randomized Controlled Trial
Multicenter Study
Research Support, Non-U.S. Gov't

Abstract

ABSTRACT: Patients with paroxysmal nocturnal hemoglobinuria (PNH) experience complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Pegcetacoplan, a C3 inhibitor, demonstrated sustained improvements in hematologic and clinical parameters in the phase 3 PEGASUS trial in patients with PNH who remained anemic despite C5 inhibitor therapy. The present post hoc analysis describes 26 hemolysis adverse events (AEs) experienced in 19 patients during pegcetacoplan therapy in PEGASUS and baseline patient characteristics potentially associated with increased hemolysis risk. Lactate dehydrogenase (LDH) >=2x the upper limit of normal (ULN) was observed in 19 events, including 2 with LDH >=10x ULN. All patients experienced decreased hemoglobin during hemolysis (mean decrease, 3.0 g/dL). In 16 events (62%), a potential complement-amplifying condition underlying the event could be identified. Hemolysis AEs led to study discontinuation in 5 patients. However, of 26 hemolysis AEs, 17 (65%) were manageable without pegcetacoplan discontinuation. A greater proportion of patients with hemolysis AEs (n = 19) had key characteristics of higher disease activity at baseline compared to patients without hemolysis AEs (n = 61), namely higher-than-label eculizumab dose (53% vs 23%), detectable CH50 (total complement function; 74% vs 54%), and >=4 transfusions in the previous 12 months (68% vs 51%). These characteristics may be useful predictors of potential future hemolysis events. This trial was registered at www.ClinicalTrials.gov as #NCT03500549.