Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison

Objective In the absence of a head-to-head study, we assessed the comparative effectiveness of pegcetacoplan, a targeted C3 complement inhibitor, vs. ravulizumab, a C5 complement inhibitor, among patients with paroxysmal nocturnal hemoglobinuria (PNH) previously treated with eculizumab using matching-adjusted indirect comparison methodology. Methods Individual patient data from the PEGASUS study (NCT03500549) comparing pegcetacoplan and eculizumab enabled adjustment for baseline differences compared with published results from the ALXN1210-PNH-302 study (NCT03056040), comparing ravulizumab and eculizumab. Adjusted differences and 95% confidence intervals (CIs) were computed via weighted Wald tests for comparisons of pegcetacoplan vs. ravulizumab, anchored to the common comparator eculizumab. Results Sixty-eight patients from PEGASUS (36 pegcetacoplan; 32 eculizumab) and 195 from ALXN1210-PNH-302 (97 ravulizumab; 98 eculizumab) were included. Compared with ravulizumab, treatment with pegcetacoplan was associated with more transfusion avoidance (adjusted difference [95% CI] = +71.4% [53.5%, 89.3%]), hemoglobin level stabilization (+75.5% [56.4%, 94.6%]), lactate dehydrogenase (LDH) level normalization (+64.0% [41.8%, 86.1%]), and fewer blood transfusions (-5.7 units [-7.2, -4.2]). Additionally, patients who received pegcetacoplan experienced clinically meaningful improvements in fatigue (+8.2 points [3.8, 12.6]), global health status (+9.6 points [0.1, 19.0]), physical functioning (+11.5 points [3.6, 19.5]), and fatigue symptoms (-13.3 points [-23.7, -3.0]), compared with ravulizumab. Mean change from baseline in LDH level was not significantly different for pegcetacoplan vs. ravulizumab. Conclusions Results suggest that among patients previously treated with eculizumab, clinical, hematological, and quality of life endpoints were better for patients who received the C3 complement inhibitor pegcetacoplan vs. patients who received ravulizumab, a C5 complement inhibitor.

Automated summary

This study compared the effectiveness of C3 complement inhibitor pegcetacoplan and C5 complement inhibitor ravulizumab among PNH patients previously treated with eculizumab. Results showed that patients treated with pegcetacoplan had better outcomes in terms of transfusion avoidance, hemoglobin stabilization, LDH normalization, and blood transfusion reduction compared to patients receiving ravulizumab. Additionally, pegcetacoplan led to improvements in fatigue, global health status, physical functioning, and fatigue symptoms in comparison to ravulizumab.