Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison

Advances in Therapy, 2023


In the absence of head-to-head trials, this study compared treatment outcomes with the C3 complement inhibitor pegcetacoplan versus the C5 complement inhibitor eculizumab or ravulizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH).


A matching-adjusted indirect comparison was conducted using individual patient data from the pegcetacoplan arm of the PRINCE trial (NCT04085601; n = 34) and aggregate data from the ravulizumab (n = 125) and eculizumab (n = 121) arms of the ALXN1210-PNH-301 trial (NCT03056040). Clinical and quality of life endpoints were evaluated after matching patients in the two trials on baseline characteristics. The weighted Wald test with 95% confidence interval was used to compare categorical and continuous variables (i.e., weighted chi-squared and z tests, respectively). Bias factor analysis was performed to quantify the extent of residual bias from unmeasured confounders.


After weighting, treatment with pegcetacoplan was associated with statistically significant improvements in most clinical endpoints compared with ravulizumab or eculizumab treatment. These included: greater absolute and percent reductions in lactate dehydrogenase (LDH) level and increase in hemoglobin level from baseline; shorter time to first occurrence of LDH normalization; larger proportions of patients achieving hemoglobin stabilization and avoiding transfusion, with fewer packed red blood cell units transfused; and a smaller proportion of patients experiencing breakthrough hemolysis (all p < 0.05). Patients receiving pegcetacoplan also had a greater increase in general health status score from baseline compared with those receiving C5 complement inhibitors.


Pegcetacoplan provides clinical benefits as first-line treatment for complement inhibitor-naïve patients with PNH.

View abstract


Wong R, Fishman J, Wilson K, Yeh M, Al-Adhami M, Zion A, Yee CW, Huynh L, Duh MS