Pegcetacoplan May Reduce Fatigue in PNH Accompanied by Anemia

For patients with paroxysmal nocturnal hemoglobinuria (PNH), starting or switching to pegcetacoplan could reduce feelings of fatigue and improve their hematologic outcomes. These conclusions are based off of a recent study published in PLoS One that investigated the efficacy of pegcetacoplan for PNH accompanied by mild or moderate anemia in patients who were either naive to complement component 5 inhibitors (C5is) or had previously received eculizumab.¹

PNH stems from a genetic abnormality that negatively influences the function of blood platelets and red blood cells.² Anemia is a fairly common consequence of PNH. This effect results from added pressure on the bone marrow to produce and replace red blood cells that have been destroyed because of this condition. When an individual’s bone marrow cannot keep up with its replacement efforts, those affected can experience persistent bouts of fatigue and feelings of tiredness that impact their day-to-day living.

Despite treatment, some patients with PNH still experience anemia | image credit: Caterpillar - stock.adobe.com

Patients with PNH often derive benefits from C5is like ravulizumab and eculizumab; however, as the present authors note, these patients may still struggle with chronic anemia.¹ By starting patients with PNH on pegcetacoplan, a complement component 3–targeted therapy, the current investigation sought to determine whether initiating this therapy could counteract anemic effects and benefit patients’ fatigue, among other outcomes.

To accomplish this, the authors gathered patients with PNH, with mild/moderate anemia, who were participants in the following clinical trials: PADDOCK (NCT02588833; n = 6), PRINCE (NCT04085601; n = 8), or PEGASUS (NCT03500549; n = 11). Broadly, these trials studied the efficacy of pegcetacoplan in complement inhibitor–naive patients (PADDOCK), compared pegcetacoplan with supportive care measures (PRINCE), or compared pegcetacoplan with eculizumab (PEGASUS). Patients were included if they had baseline hemoglobin levels of at least 10 g/dL and had not received a blood transfusion in the 2 weeks prior to baseline measurements.

In total, 25 patients were included in this analysis of 16-week monotherapy with pegcetacoplan. Across all 3 trials, individual and average hemoglobin levels increased and surpassed 12 g/dL from baseline to week 16 (PADDOCK: 10.5 g/dL vs 12.7 g/dL; PRINCE: 11.3 g/dL vs 14 g/dL; PEGASUS: 10.2 g/dL vs 12.8 g/dL). Furthermore, the amount of patients whose hemoglobin levels exceeded 12 g/dL grew throughout each trial after 16 weeks of pegcetacoplan. The authors noted 2 patients who exhibited decreases in hemoglobin, but these incidences were linked with breakthrough hemolysis events that were unrelated to pegcetacoplan. Absolute reticulocyte counts normalization was also observed in at least 75% of included patients across the 3 trials.

The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT Fatigue) was used to assess fatigue measures. These results improved from baseline to week 16 in both the PADDOCK (mean: 36.7 vs 45.2) and PRINCE (mean: 35.6 vs 46.3) trials, which rose above the normal levels in the general population, the authors wrote. Participants in the PEGASUS study also had increases to their FACIT-Fatigue, but these did not grow above the general population norm.

Overall, pegcetacoplan was well tolerated in patients, with no serious adverse events occurring that were related to treatment.

“Pegcetacoplan normalized hematologic parameters and reduced fatigue in substantial percentages of clinical trial patients with PNH with mild or moderate anemia,” the authors concluded. “The current findings suggest that patients with mild or moderate anemia benefited from targeted C3 therapy and should strive for additional improvement in hematologic parameters.”

References

1. 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

2. Paroxysmal nocturnal hemoglobinuria. Cleveland Clinic. Updated April 24, 2022. Accessed August 27, 2024. https://my.clevelandclinic.org/health/diseases/22871-paroxysmal-nocturnal-hemoglobinuria