Pegcetacoplan was superior to eculizumab in improving outcomes in patients with paroxysmal nocturnal hemoglobinuria (PNH) according to a recent study published in the New England Journal of Medicine.

PNH is a rare, acquired hematologic disease that causes fatigue, increased risk of thrombosis, and bone marrow dysfunction. People with PNH often have chronic hemolysis.

C5 inhibitors control intravascular hemolysis and have reduced life-threatening complications of PNH, transforming outcomes for these patients. However, extravascular hemolysis still occurs in patients being treated with C5 inhibitors, such as eculizumab, leading to anemia and the need for blood transfusions. Pegcetacoplan controls intravascular and extravascular hemolysis by targeting complement C3.

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The phase 3, open-label PEGASUS trial compared the safety and efficacy of pegcetacoplan to eculizumab in patients with PNH and a hemoglobin level of less than 10.5 g per deciliter. The current study presented primary data from the 16-week randomized, controlled period.

A total of 80 patients were enrolled in the trial, with 41 assigned to receive pegcetacoplan and 39 assigned to receive eculizumab. Patients in the pegcetacoplan arm had a mean change in hemoglobin from baseline to week 16 of 2.37 g per deciliter, while patients in the eculizumab had a mean change of -1.47 g per deciliter (P <.001).

Both groups experienced similar rates of adverse events (36 patients with pegcetacoplan and 34 patients with eculizumab). Injection-site reactions and diarrhea were more common in the pegcetacoplan group. Breakthrough hemolysis, headache and fatigue were more common with eculizumab.

One concern with a C3 complement inhibitor is a heightened risk of infection. In this study, infection rates were similar in both treatment groups, but longer-term studies are needed.

Patients receiving eculizumab remained severely anemic, continued to be transfusion dependent, and experienced fatigue. Patients in the pegcetacoplan group had normal levels of hemoglobin at week 16, with 85% of patients doing so transfusion-free. At week 16, 71% of patients in the pegcetacoplan group had normalization of LDH levels versus 15% of patients in the eculizumab group.

Overall, pegcetacoplan controlled markers of extravascular hemolysis and intravascular hemolysis. Patients in the pegcetacoplan group also reported an improvement in fatigue. The authors concluded that pegcetacoplan was superior to eculizumab in terms of improvement in hematologic and clinical variables.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384(11):1028-1037. doi:10.1056/NEJMoa2029073