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

Publication ,  Journal Article
Peffault de Latour, R; Griffin, M; Kelly, RJ; Szer, J; de Castro, C; Horneff, R; Tan, L; Yeh, M; Panse, J
Published in: Blood Adv
June 11, 2024

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) ≥2× the upper limit of normal (ULN) was observed in 19 events, including 2 with LDH ≥10× 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.

Duke Scholars

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

June 11, 2024

Volume

8

Issue

11

Start / End Page

2718 / 2725

Location

United States

Related Subject Headings

  • Middle Aged
  • Male
  • Humans
  • Hemolysis
  • Hemoglobinuria, Paroxysmal
  • Female
  • Complement Inactivating Agents
  • Complement C3
  • Antibodies, Monoclonal, Humanized
  • Aged
 

Citation

APA
Chicago
ICMJE
MLA
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Peffault de Latour, R., Griffin, M., Kelly, R. J., Szer, J., de Castro, C., Horneff, R., … Panse, J. (2024). Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv, 8(11), 2718–2725. https://doi.org/10.1182/bloodadvances.2024012672
Peffault de Latour, Régis, Morag Griffin, Richard J. Kelly, Jeff Szer, Carlos de Castro, Regina Horneff, Lisa Tan, Michael Yeh, and Jens Panse. “Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.Blood Adv 8, no. 11 (June 11, 2024): 2718–25. https://doi.org/10.1182/bloodadvances.2024012672.
Peffault de Latour R, Griffin M, Kelly RJ, Szer J, de Castro C, Horneff R, et al. Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2024 Jun 11;8(11):2718–25.
Peffault de Latour, Régis, et al. “Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.Blood Adv, vol. 8, no. 11, June 2024, pp. 2718–25. Pubmed, doi:10.1182/bloodadvances.2024012672.
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. Blood Adv. 2024 Jun 11;8(11):2718–2725.

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

June 11, 2024

Volume

8

Issue

11

Start / End Page

2718 / 2725

Location

United States

Related Subject Headings

  • Middle Aged
  • Male
  • Humans
  • Hemolysis
  • Hemoglobinuria, Paroxysmal
  • Female
  • Complement Inactivating Agents
  • Complement C3
  • Antibodies, Monoclonal, Humanized
  • Aged