Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison
Rachel H. Bhak, Nikita Mody‐Patel, Scott B. Baver, Colin Kunzweiler, Christopher Yee, Sanjana Sundaresan, Natalia Swartz, Mei Sheng Duh, Sangeeta Krishnan, Sujata P. Sarda
Abstract
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: 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.