Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition
Issued Date
2024-01-01
Resource Type
ISSN
03618609
eISSN
10968652
Scopus ID
2-s2.0-85196202397
Journal Title
American Journal of Hematology
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Hematology (2024)
Suggested Citation
Röth A., He G., Tong H., Lin Z., Wang X., Chai-Adisaksopha C., Lee J.H., Brodsky A., Hantaweepant C., Dumagay T.E., Demichelis-Gómez R., Rojnuckarin P., Sun J., Höglund M., Jang J.H., Gaya A., Silva F., Obara N., Kelly R.J., Beveridge L., Buatois S., Chebon S., Gentile B., Lundberg P., Sreckovic S., Nishimura J.i., Risitano A., Han B. Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition. American Journal of Hematology (2024). doi:10.1002/ajh.27412 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/99001
Title
Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition
Author(s)
Röth A.
He G.
Tong H.
Lin Z.
Wang X.
Chai-Adisaksopha C.
Lee J.H.
Brodsky A.
Hantaweepant C.
Dumagay T.E.
Demichelis-Gómez R.
Rojnuckarin P.
Sun J.
Höglund M.
Jang J.H.
Gaya A.
Silva F.
Obara N.
Kelly R.J.
Beveridge L.
Buatois S.
Chebon S.
Gentile B.
Lundberg P.
Sreckovic S.
Nishimura J.i.
Risitano A.
Han B.
He G.
Tong H.
Lin Z.
Wang X.
Chai-Adisaksopha C.
Lee J.H.
Brodsky A.
Hantaweepant C.
Dumagay T.E.
Demichelis-Gómez R.
Rojnuckarin P.
Sun J.
Höglund M.
Jang J.H.
Gaya A.
Silva F.
Obara N.
Kelly R.J.
Beveridge L.
Buatois S.
Chebon S.
Gentile B.
Lundberg P.
Sreckovic S.
Nishimura J.i.
Risitano A.
Han B.
Author's Affiliation
Siriraj Hospital
University of Tsukuba Hospital
Graduate School of Medicine
Jiangsu Province Hospital
Azienda Ospedaliera S.G. Moscati
University of the Philippines Manila
Asan Medical Center
Faculty of Medicine, Chiang Mai University
Hospital Clinic Barcelona
Zhejiang University School of Medicine
Genentech, Inc
University of Leeds, School of Medicine
King Chulalongkorn Memorial Hospital
Nantong University
Samsung Medical Center, Sungkyunkwan university
Fudan University
Instituto Nacional de la Nutrición Salvador Zubiran
Hospital de Clínicas "José de San Martín"
Peking Union Medical College Hospital
F. Hoffmann-La Roche AG
Universitätsklinikum Essen
Uppsala Universitet
Southern Medical University
Centro Hospitalar do Baixo Vouga
University of Tsukuba Hospital
Graduate School of Medicine
Jiangsu Province Hospital
Azienda Ospedaliera S.G. Moscati
University of the Philippines Manila
Asan Medical Center
Faculty of Medicine, Chiang Mai University
Hospital Clinic Barcelona
Zhejiang University School of Medicine
Genentech, Inc
University of Leeds, School of Medicine
King Chulalongkorn Memorial Hospital
Nantong University
Samsung Medical Center, Sungkyunkwan university
Fudan University
Instituto Nacional de la Nutrición Salvador Zubiran
Hospital de Clínicas "José de San Martín"
Peking Union Medical College Hospital
F. Hoffmann-La Roche AG
Universitätsklinikum Essen
Uppsala Universitet
Southern Medical University
Centro Hospitalar do Baixo Vouga
Corresponding Author(s)
Other Contributor(s)
Abstract
Crovalimab 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.