Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening 
hematologic disease characterized by chronic complement-mediated hemolysis and 
thrombosis. Despite treatment with eculizumab, a C5 inhibitor, 72% of 
individuals remain anemic. Pegcetacoplan (APL-2), a PEGylated C3 inhibitor, has 
the potential to provide more complete hemolysis control in patients with PNH. 
This open-label, phase Ib study was designed to assess the safety, tolerability, 
and pharmacokinetics of pegcetacoplan in subjects with PNH who remained anemic 
during treatment with eculizumab. Pharmacodynamic endpoints were also assessed 
as an exploratory objective of this study. Data are presented for six subjects 
in cohort 4 who received treatment for up to 2 years. In total, 427 
treatment-emergent adverse events (TEAEs) were reported, 68 of which were 
possibly related to the study drug. Eight serious TEAEs occurred in two 
subjects; three of these events were considered possibly related to the study 
drug. Pegcetacoplan pharmacokinetic concentrations accumulated with repeated 
dosing, and steady state was reached at approximately 6-8 weeks. Lactate 
dehydrogenase levels were well controlled by eculizumab at baseline. 
Pegcetacoplan increased hemoglobin levels and decreased both reticulocyte count 
and total bilirubin in all six subjects. Improvements were observed in 
Functional Assessment of Chronic Illness Therapy Fatigue scores. Two subjects 
discontinued for reasons unrelated to pegcetacoplan. All four subjects who 
completed the study transitioned to pegcetacoplan monotherapy following 
eculizumab discontinuation and avoided transfusions. In this small study, 
pegcetacoplan therapy was generally well-tolerated, and resulted in an improved 
hematological response by achieving broad hemolysis control, enabling eculizumab 
discontinuation.