Ravulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete,
and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority
of ravulizumab to eculizumab in complement inhibitor-naive adults with paroxysmal
nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogenase (LDH) ≥1.5 times
the upper limit of normal and at least 1 PNH symptom were randomized 1:1 to receive
ravulizumab or eculizumab for 183 days (N = 246). Coprimary efficacy end points were
proportion of patients remaining transfusion-free and LDH normalization. Secondary
end points were percent change from baseline in LDH, change from baseline in Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, proportion of patients
with breakthrough hemolysis, stabilized hemoglobin, and change in serum free C5. Ravulizumab
was noninferior to eculizumab for both coprimary and all key secondary end points
(Pinf < .0001): transfusion avoidance (73.6% vs 66.1%; difference of 6.8% [95% confidence
interval (CI), -4.66, 18.14]), LDH normalization (53.6% vs 49.4%; odds ratio, 1.19
[0.80, 1.77]), percent reduction in LDH (-76.8% vs -76.0%; difference [95% CI], -0.83%
[-5.21, 3.56]), change in FACIT-Fatigue score (7.07 vs 6.40; difference [95% CI],
0.67 [-1.21, 2.55]), breakthrough hemolysis (4.0% vs 10.7%; difference [95% CI], -6.7%
[-14.21, 0.18]), and stabilized hemoglobin (68.0% vs 64.5%; difference [95% CI], 2.9
[-8.80, 14.64]). The safety and tolerability of ravulizumab and eculizumab were similar;
no meningococcal infections occurred. In conclusion, ravulizumab given every 8 weeks
achieved noninferiority compared with eculizumab given every 2 weeks for all efficacy
end points, with a similar safety profile. This trial was registered at www.clinicaltrials.gov
as #NCT02946463.