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Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.
Blood. 2019 02 07; 133(6):530-539.Blood

Abstract

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.

Authors+Show Affiliations

Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Hematology Transplant Unit, Hôpital Saint-Louis, Paris, France.Hematology Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.Hematology, Hemorio, Rio de Janeiro, Brazil.Department of Haematology, University of São Paulo Medical School, São Paulo, Brazil.Division of Hematology & Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.Outpatient Department for Hematology, Oncology and Chemotherapy, S. P. Botkin Hospital, Moscow, Russia.Alexion Pharmaceuticals, Inc, Boston, MA.Alexion Pharmaceuticals, Inc, Boston, MA.Alexion Pharmaceuticals, Inc, Boston, MA.Alexion Pharmaceuticals, Inc, Boston, MA.Alexion Pharmaceuticals, Inc, Boston, MA.Institute of Transfusion Medicine, University of Ulm, Ulm, Germany. Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany; and.Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30510080

Citation

Lee, Jong Wook, et al. "Ravulizumab (ALXN1210) Vs Eculizumab in Adult Patients With PNH Naive to Complement Inhibitors: the 301 Study." Blood, vol. 133, no. 6, 2019, pp. 530-539.
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):530-539.
Lee, J. W., Sicre de Fontbrune, F., Wong Lee Lee, L., Pessoa, V., Gualandro, S., Füreder, W., Ptushkin, V., Rottinghaus, S. T., Volles, L., Shafner, L., Aguzzi, R., Pradhan, R., Schrezenmeier, H., & Hill, A. (2019). Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood, 133(6), 530-539. https://doi.org/10.1182/blood-2018-09-876136
Lee JW, et al. Ravulizumab (ALXN1210) Vs Eculizumab in Adult Patients With PNH Naive to Complement Inhibitors: the 301 Study. Blood. 2019 02 7;133(6):530-539. PubMed PMID: 30510080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. AU - Lee,Jong Wook, AU - Sicre de Fontbrune,Flore, AU - Wong Lee Lee,Lily, AU - Pessoa,Viviani, AU - Gualandro,Sandra, AU - Füreder,Wolfgang, AU - Ptushkin,Vadim, AU - Rottinghaus,Scott T, AU - Volles,Lori, AU - Shafner,Lori, AU - Aguzzi,Rasha, AU - Pradhan,Rajendra, AU - Schrezenmeier,Hubert, AU - Hill,Anita, Y1 - 2018/12/03/ PY - 2018/09/26/received PY - 2018/11/18/accepted PY - 2018/12/5/pubmed PY - 2019/10/19/medline PY - 2018/12/5/entrez SP - 530 EP - 539 JF - Blood JO - Blood VL - 133 IS - 6 N2 - 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. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/30510080/Ravulizumab__ALXN1210__vs_eculizumab_in_adult_patients_with_PNH_naive_to_complement_inhibitors:_the_301_study_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2018-09-876136 DB - PRIME DP - Unbound Medicine ER -