OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by complement-mediated hemolysis. The most reported PNH-symptom is fatigue. Pegcetacoplan was superior to eculizumab in improving hemoglobin levels in adults with PNH (Phase 3 PEGASUS trial [NCT03500549]). However, improvement in fatigue, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and time to improvement is also valuable to clinicians/patients considering treatment options. This post hoc analysis compared pegcetacoplan to eculizumab in time to a 2-level improvement for FACIT-Fatigue item-level measures within 16 weeks using the Kaplan-Meier curve and log-rank test.

METHODS: PEGASUS enrolled 80 patients with PNH (≥18 years, hemoglobin <10.5 g/dL; stable eculizumab ≥3 months). Patients completed a 4-week eculizumab+pegcetacoplan run-in period followed by 1:1 randomization to pegcetacoplan (n=41; 1080 mg subcutaneously twice weekly) or eculizumab (n=39) through Week 16. Fatigue was assessed using FACIT-Fatigue, a 5-point Likert scale instrument (0=very much, 4=not at all; total score 0-52), where we investigated the the time to a 2-level improvement on an individual item.

RESULTS: Pegcetacoplan led to a larger mean (SD) FACIT-Fatigue total score increase from baseline to Week 16 (baseline: 32.16 [11.38]; Week 16: 42.49 [8.83]) versus eculizumab (baseline 31.55 [12.51]; Week 16: 34.67 [16.35]). A higher rate of a 2-level improvement was observed in pegcetacoplan versus eculizumab in 10/13 FACIT-Fatigue item-level measures within 16 weeks. Specifically, pegcetacoplan led to a higher rate of improvement on “I feel fatigued” (log-rank test p=0.0189), “I have trouble finishing things” (p=0.0023) and “I need help doing usual activities” (p=0.0049) compared to eculizumab. Based on the Kaplan-Meier analysis, pegcetacoplan led to a higher probability of a rapid (2 Week) 2-level improvement on “I feel fatigued” (55.6%) than eculizumab (33.3%).

CONCLUSIONS: Pegcetacoplan treatment led to a higher rate and probability of a rapid 2-level improvement in most FACIT-Fatigue item-level measures versus eculizumab.