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

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

  • Blood. 2019 Feb 7;133(6):530-539. doi: 10.1182/blood-2018-09-876136.
Jong Wook Lee 1,  Flore Sicre de Fontbrune 2,  Lily Wong Lee Lee 3,  Viviani Pessoa 4,  Sandra Gualandro 5,  Wolfgang Füreder 6,  Vadim Ptushkin 7,  Scott T Rottinghaus 8,  Lori Volles 8,  Lori Shafner 8,  Rasha Aguzzi 8,  Rajendra Pradhan 8,  Hubert Schrezenmeier 9 10,  Anita Hill 11
Affiliations

Affiliations

  • 1 Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • 2 Hematology Transplant Unit, Hôpital Saint-Louis, Paris, France.
  • 3 Hematology Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.
  • 4 Hematology, Hemorio, Rio de Janeiro, Brazil.
  • 5 Department of Haematology, University of São Paulo Medical School, São Paulo, Brazil.
  • 6 Division of Hematology & Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
  • 7 Outpatient Department for Hematology, Oncology and Chemotherapy, S. P. Botkin Hospital, Moscow, Russia.
  • 8 Alexion Pharmaceuticals, Inc, Boston, MA.
  • 9 Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
  • 10 Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany; and.
  • 11 Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.
PMID: 30510080 DOI: 10.1182/blood-2018-09-876136
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.

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