Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition

Author:

Röth Alexander1ORCID,He Guangsheng2ORCID,Tong Hongyan3,Lin Zenghua4,Wang Xiaoqin5,Chai‐Adisaksopha Chatree6,Lee Je‐Hwan7ORCID,Brodsky Andres8,Hantaweepant Chattree9,Dumagay Teresita E.10,Demichelis‐Gómez Roberta11ORCID,Rojnuckarin Ponlapat12,Sun Jing13,Höglund Martin14,Jang Jun Ho15,Gaya Anna16,Silva Fernando17,Obara Naoshi18,Kelly Richard J.19,Beveridge Leigh20,Buatois Simon21,Chebon Sammy21,Gentile Brittany20,Lundberg Pontus21,Sreckovic Sasha20,Nishimura Jun‐ichi22,Risitano Antonio23ORCID,Han Bing24

Affiliation:

1. Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen University of Duisburg‐Essen Essen Germany

2. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Collaborative Innovation Center for Cancer Personalized Medicine Nanjing China

3. Department of Hematology, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China

4. Department of Hematology Affiliated Hospital of Nantong University Jiangsu China

5. Department of Hematology, Huashan Hospital Fudan University Shanghai China

6. Faculty of Medicine Chiang Mai University Chiang Mai Thailand

7. Department of Hematology, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea

8. Hematology Division, Hospital de Clínicas José de San Martín University of Buenos Aires Buenos Aires Argentina

9. Faculty of Medicine Siriraj Hospital, Division of Hematology, Department of Medicine Mahidol University Bangkok Thailand

10. Division of Hematology, Department of Medicine University of the Philippines, Philippine General Hospital Manila Philippines

11. Department of Hematology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City Mexico

12. Center of Excellence in Translational Hematology, Faculty of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Bangkok Thailand

13. Department of Hematology, Nanfang Hospital Southern Medical University Guangzhou China

14. Department of Medical Sciences Uppsala University Uppsala Sweden

15. Department of Hematology‐Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea

16. Hematology Department Hospital Clínic de Barcelona Barcelona Spain

17. Hematology Department Centro Hospitalar do Baixo Vouga Aveiro Portugal

18. Department of Hematology University of Tsukuba Hospital Ibaraki Japan

19. Division of Haematology and Immunology Leeds Institute of Medical Research at St James's, University of Leeds Leeds UK

20. Genentech, Inc. South San Francisco California USA

21. F. Hoffmann‐La Roche Ltd Basel Switzerland

22. Osaka University Graduate School of Medicine Osaka Japan

23. Hematology and BMT Unit AORN San Giuseppe Moscati Avellino Italy

24. Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College Chinese Academy of Medical Sciences Peking China

Abstract

AbstractCrovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low‐volume self‐administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open‐label, multicenter, phase 3 trial evaluating the non‐inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor‐naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co‐primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT‐Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non‐inferior to eculizumab in the co‐primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, −2.8 [−15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, −3.9 [−14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [−11.4, 16.3]). A clinically meaningful improvement in FACIT‐Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit–risk profile of crovalimab.

Publisher

Wiley

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