Indirect treatment comparisons find enhanced effectiveness of pegcetacoplan versus crovalimab in both complement inhibitor-naïve and -experienced patients with paroxysmal nocturnal hemoglobinuria

Aim: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare hematological condition, which if undertreated, is associated with significant morbidity and early mortality. This indirect treatment comparison (ITC) evaluated the effectiveness of pegcetacoplan (the first approved proximal inhibitor) versus crovalimab, a new C5i inhibitor (C5i), for treatment of PNH in C5i-naive and C5i-experienced patients. Materials & methods: In the C5i-naive, an unanchored matching-adjusted indirect comparison (MAIC) was conducted with patient-level data for pegcetacoplan-versus-best-supportive-care from PRINCE ( NCT0408560 ) and published data for crovalimab-versus-eculizumab from COMMODORE 2 ( NCT04434092 )/COMMODORE 3 ( NCT04654468 ). In the C5i-experienced ITC (Bucher’s method), patient-level data were from PEGASUS ( NCT03500549 ; pegcetacoplan vs eculizumab) and aggregated data from COMMODORE 1 ( NCT04432584 ; crovalimab-vs-eculizumab). Evaluated outcomes in both settings included red-blood-cell transfusion-avoidance; hemoglobin (Hb) stabilization; hemolysis control; mean change-from-baseline on Functional Assessment of Chronic Illness Therapy–Fatigue total scores; additionally, the C5i-experienced ITC evaluated, mean change-from-baseline to week-25 for red blood cell units and domain scores on the European Organization for Research and Treatment of Cancer instrument. Results: Pegcetacoplan versus crovalimab in the C5i-naive was associated with significantly (p < 0.05) higher probabilities of transfusion-avoidance and Hb stabilization, and greater odds of hemolysis control. In the C5i-experienced, all outcomes significantly (p < 0.05) favored pegcetacoplan. Conclusion: Pegcetacoplan provides high clinical advantages across the full PNH treatment pathway.