Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.

Authors:
Jong Wook Lee
Jong Wook Lee
Seoul St. Mary's Hospital
South Korea
Viviani Pessoa
Viviani Pessoa
State Institute of Hematology
Sandra Gualandro
Sandra Gualandro
Hospital das Clínicas
Brazil
Vadim Ptushkin
Vadim Ptushkin
S.P. Botkin Hospital
Scott T Rottinghaus
Scott T Rottinghaus
Clinical Affairs

Blood 2019 Feb 3;133(6):530-539. Epub 2018 Dec 3.

Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.

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 ( < .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.

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Source
http://dx.doi.org/10.1182/blood-2018-09-876136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367644PMC

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February 2019
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