Paroxysmal nocturnal hemoglobinuria (PNH) is a
rare disease characterized by
complement-mediated
hemolysis.
Pegcetacoplan is the first C3-targeted
therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with
anemia despite C5-targeted
therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of
pegcetacoplan vs control (supportive care only; eg,
blood transfusions,
corticosteroids, and supplements) in
complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening. Patients received
pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were
hemoglobin stabilization (avoidance of >1-g/dL decrease in
hemoglobin levels without transfusions) from baseline through week 26 and
lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received
pegcetacoplan (n = 35) or control (n = 18).
Pegcetacoplan was superior to control for
hemoglobin stabilization (
pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change:
pegcetacoplan, -1870.5 U/L; control, -400.1 U/L; difference, -1470.4 U/L; 95% CI, -2113.4 to -827.3; P < .0001).
Pegcetacoplan was well tolerated. No
pegcetacoplan-related adverse events were serious, and no new safety signals were observed.
Pegcetacoplan rapidly and significantly stabilized
hemoglobin and reduced LDH in
complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601.