Abstract
In the phase III randomized, open-label PRINCE trial (NCT04085601), pegcetacoplan demonstrated superior efficacy versus control treatment (excluding complement inhibitors) among treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH); no head-to-head trials comparing pegcetacoplan to complement inhibitors have previously been conducted in this patient population. To indirectly compare the effectiveness of pegcetacoplan versus ravulizumab and eculizumab in complement inhibitor-naïve PNH patients. Cross-trial comparisons were conducted using individual patient data from PRINCE and published aggregate data for ravulizumab and eculizumab from ALXN1210-PNH-301. Propensity score weighting using logistic regression was employed to balance baseline characteristics across studies. Outcomes at 26 weeks were compared using unanchored matching-adjusted indirect comparison (MAIC) and weighted Wald statistical tests. MAIC of clinical trial data. Complement inhibitor-naïve patients with PNH matched on Asian race, age at first infusion, sex, and baseline EORTC-QLQ-C30 General Health score Interventions: N/A. Transfused packed red blood cell (PRBC) units, time to first LDH normalization (<1x ULN [246 U/L] without transfusions during the randomized controlled period), breakthrough hemolysis, major adverse vascular events (MAVEs), mean change in hemoglobin level, and change in FACIT-Fatigue and EORTC-QLQ-C30 scores. Before matching, statistically significant differences existed among pegcetacoplan (n=34), ravulizumab (n=125), and eculizumab (n=121) arms on White and American Indian/Alaska Native race and baseline LDH (all P<0.001). After matching pegcetacoplan to each of the comparator arms, most characteristics were well-balanced (mean age: 44.8-46.2 years, 43.0%-48.0% female, mean hemoglobin: 9.4-9.7 g/dL). At week 26, pegcetacoplan was associated with significantly greater improvements in hemoglobin levels versus ravulizumab (mean: 1.58 g/dL [16.8%]) and eculizumab (1.78 g/dL [19.5%]) and in EORTC-QLQ-C30 General Health scores (mean: 12.9 and 12.5 points, all P<0.05). Significantly fewer units of PRBCs transfused were estimated for pegcetacoplan versus ravulizumab and eculizumab (mean: -4.1 and -4.6 units, respectively, all P<0.0001) and faster LDH normalization (-8.3 and -13.1 days, P<0.0001 and P=0.0095). The proportions with breakthrough hemolysis or MAVEs, and changes in FACIT-Fatigue and EORTC-QLQ-C30 Physical Functioning or Fatigue scores, were similar between arms. This MAIC demonstrates that pegcetacoplan is more efficacious than ravulizumab or eculizumab among complement inhibitor-naïve patients with PNH.
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