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Research Article
24 August 2026

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

Authors: Raymond Siu Ming Wong https://orcid.org/0000-0002-9011-4268, Koo Wilson https://orcid.org/0000-0002-8732-8249 [email protected], Zalmai Hakimi https://orcid.org/0000-0001-5835-8599, Mikolaj Parkitny https://orcid.org/0009-0007-8652-6749, Piotr Wojciechowski https://orcid.org/0000-0001-8400-1171, Catherine Flynn https://orcid.org/0000-0002-9740-6757, and Francis Fatoye https://orcid.org/0000-0002-3502-3953Author Info & Affiliations
Volume 15, Number 10
https://doi.org/10.57264/cer-2026-0015
PDFFormats

Abstract

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.

Plain language summary

What is this article about?

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare blood condition, which if undertreated, can progress and lead to severe health complications and early death. To help physicians and other healthcare decisionmakers choose the appropriate drug for PNH, this study looked at the effectiveness of pegcetacoplan (the first approved drug in the class of proximal inhibitors) versus crovalimab (a new drug in a class of drugs called C5 inhibitors), for treatment of PNH in patients with and without prior treatment with C5 inhibitors.

What methodology/protocol is described?

Because there are no head-to-head (or direct) comparisons for these two drugs, this study used a method called indirect comparison, using data from each of the drug’s separate clinical studies. The effectiveness of each drug was compared by looking at blood transfusion avoidance, red blood cell (RBC) stabilization, red blood cell destruction and fatigue. For patients who had prior treatment with C5 inhibitors, the study also evaluated their health-related quality of life.

What were the results?

The study showed that pegcetacoplan patients who never had prior C5 inhibitor treatment were more likely than crovalimab patients to avoid transfusions, while also experiencing RBC stabilization and control of RBC destruction. Pegcetacoplan patients who had prior treatment with C5 inhibitors had better results for effectiveness on all the measures studied.

Why is this important?

This study may assist physicians and other healthcare decisionmakers choose the most appropriate treatments for patients with PNH.

Supplementary Material

File (supplementary data.pdf)
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