One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab

Abstract

Ravulizumab every 8 weeks showed non-inferiority to eculizumab every 2 weeks in a 26-week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab-ravulizumab and 5.8% (27%) with eculizumab-ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab-ravulizumab, n = 3; eculizumab-ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 μg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab-ravulizumab, 86.5%; eculizumab-ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 μg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.

Keywords: breakthrough hemolysis; complement inhibitor; hemoglobin; paroxysmal nocturnal hemoglobinuria; quality of life; transfusion.

FIGURE 1

(A) Mean (95% CI) percentage change from primary evaluation period BL in LDH levels. Dashed vertical line indicates the end of the primary evaluation period. (B) Mean (95% CI) LDH levels over time. Dashed horizontal line indicates 1 × ULN, and dotted horizontal line indicates 1.5 × ULN. BL = baseline; LDH = lactate dehydrogenase; ULN = upper limit of normal

FIGURE 2

Serum free C5 levels through 52 weeks in the (A) ravulizumab‐ravulizumab arm and (B) eculizumab‐ravulizumab arm. Horizontal line in the middle of each box indicates the median, and a diamond indicates the mean. Top and bottom borders of the box represent the 75th and 25th percentiles, respectively, and whiskers represent the 1.5 interquartile range of the lower and upper quartiles. Asterisks represent values outside the interquartile range. Dashed horizontal lines indicate Serum free C5 concentration of 0.5 μg/mL. Dashed vertical line indicates the end of the primary evaluation period. BL = baseline; EOI = end of infusion