Hematologic, Fatigue Benefits From Pegcetacoplan in PNH

The use of the complement component 3-targeted therapy pegcetacoplan produces clinical benefits in patients with paroxysmal nocturnal hemoglobinuria (PNH) and anemia, according to a post-hoc analysis published in PLOS ONE.

“Patients with PNH and mild or moderate anemia who were [complement component 5 inhibitor (C5i)]-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan,” the authors wrote.

The analysis involved 25 patients from the PADDOCK, PRINCE, and PEGASUS clinical trials with PNH and baseline hemoglobin of at least 10.0 g/dL. The six patients from PADDOCK and eight from PRINCE were C5i-naïve, and the 11 patients from PEGASUS had hemoglobin of less than 10.5 g/dL despite receiving eculizumab. All patients were administered pegcetacoplan for 16 weeks.

From baseline to week 16, mean hemoglobin concentrations increased in all three groups, from 10.5 g/dL to 12.7 g/dL in the PADDOCK patients, 11.3 g/dL to 14.0 g/dL in the PRINCE patients, and10.2 g/dL to 12.8 g/dL in the PEGASUS patients.

All three groups also saw increases in the percentage of patients who had hemoglobin of at least 12 g/dL, rising in the PADDOCK patients from 0.0% to 60.0%, in the PRINCE patients from 25.0% to 87.5%, and in the PEGASUS patients from 0.0% to 72.7%.

By week 16, sex-specific hemoglobin normalization had occurred in 40.0% of the PADDOCK patients, 62.5% of the PRINCE patients, and 63.6% of the PEGASUS patients.

“In all studies, mean [absolute reticulocyte counts (ARCs)] decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal,” the investigators added regarding patient outcomes.

Two patients in the PEGASUS trial had serious adverse events, including a case of breakthrough hemolysis, which resolved without study discontinuation, and an occurrence of post-surgery sepsis.

Reference

Panse J, Daguindau N, Okuyama S, et al. Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin ≥10 g/dL) who had received eculizumab or were naive to complement inhibitors. PLoS One. 2024;19(7):e0306407. doi:10.1371/journal.pone.0306407