Pegcetacoplan Versus Eculizumab for Change in Hemoglobin Level in Patients with Paroxysmal Nocturnal Hemoglobinuria

The phase III PEGASUS trial compared pegcetacoplan versus eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and found that pegcetacoplan induced better hemoglobin levels and clinical outcomes at 16 weeks. The results were presented at the 2020 ASH Annual Meeting.

The randomized, open-label, controlled trial included 80 adult patients with a confirmed diagnosis of PNH who had hemoglobin levels <10.5 g/dL, reticulocytes >1.0 times the upper limit of normal, platelets >50×109/L, and neutrophils >0.5 × 109/L.

Patients completed a four-week run-in period of pegcetacoplan plus eculizumab and were then randomized 1:1 to receive monotherapy pegcetacoplan 1,080 mg subcutaneously twice weekly (n=41) or eculizumab at their current dosing regimen (n=39).

At 16 weeks, there was an adjusted treatment difference of 3.84 g/dL (P<0.0001) in change in hemoglobin level (primary endpoint) with pegcetacoplan versus eculizumab. The least-squares mean changes were 2.37 g/dL (0.36) with pegcetacoplan and −1.47 g/dL (0.67) with eculizumab, both of which changed from a baseline measure of 8.7 g/dL.

At 16 weeks, a greater proportion of patients receiving pegcetacoplan achieved ≥2 g/dL improvement in hemoglobin (61% vs. 0%), hemoglobin normalization (34% vs. 0%), and hemoglobin stabilization (85% vs. 15%) in the absence of transfusion versus eculizumab.

Thirty-five patients (85.4%) treated with pegcetacoplan avoided transfusion compared with six (15.4%) treated with eculizumab, for an adjusted risk difference of 62.5% (95% confidence interval [CI], 48.3-76.8), demonstrating non-inferiority, according to the authors.

Adverse events (AEs) were reported in 36 patients (87.8%) treated with pegcetacoplan and 34 (87.2%) treated with eculizumab; seven (17.1%) and six (15.4%) patients, respectively, reported serious AEs. Common AEs associated with pegcetacoplan and eculizumab were injection site reactions (n=15; 36.6% vs. n=1; 2.6%) and diarrhea (n=9; 22.0%; vs. n=1; 2.6%). Infections were reported in 12 (29.3%) and 10 (25.6%) patients, respectively.

Four (9.8%) patients treated with pegcetacoplan and nine (23.1%) treated with eculizumab experienced breakthrough hemolysis. Three patients in the pegcetacoplan cohort discontinued treatment.

“The efficacy of pegcetacoplan validates the prevention of extravascular as well as intravascular hemolysis in PNH, leading to a potential new therapeutic option,” the researchers concluded.


Hillmen P, Szer J, Weitz IC, et al. Results of the Pegasus Phase 3 Randomized Trial Demonstrating Superiority of the C3 Inhibitor, Pegcetacoplan, Compared to Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria. Abstract 2579. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, Dec. 2-11, 2020.