MDS-254 A Matching-Adjusted Indirect Comparison of the Efficacy of Pegcetacoplan using PRINCE Trial Data versus Ravulizumab and Eculizumab in Complement Inhibitor–Naïve Patients With Paroxysmal Nocturnal Hemoglobinuria

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.