C008 | Phase Iii Commodore 2 and 1 Trials: Characterization of Breakthrough Hemolysis Events in Patients With Paroxysmal Nocturnal Hemoglobinuria Treated With Crovalimab or Eculizumab
Year: 2025
Type: article
Abstract: Crovalimab (crova), a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) dosing every 4 weeks (Q4W), was assessed vs eculizumab (ecu) in randomized, Phase III COMMODORE 2 and 1 trials. Here we report a comprehensive characterization of BTH events during the primary treatment periods of both studies. BTH was defined as presence of elevated LDH ≥2×ULN after a prior decrease to <1.5×ULN after study start and a concurrent new or worsening symptom of intravascular hemolysis. BTH events that occurred during the 24-week primary treatment period were analyzed and categorized in 1) being temporally associated with a complement-activating condition (CAC); 2) being temporally associated with suboptimal C5 inhibition; unrelated to either of the above. BTH events occurred in 10/134 pts (7%) in the crova arm and 9/69 (13%) in the ecu arm of COMMODORE 2, and 4 of 44 (9%) and 4 of 42 (10%), respectively, in COMMODORE 1. Across both studies, 14/178 pts (8%) in the crova arms and 13/111 pts (12%) in the ecu arms had BTH. In COMMODORE 2, 6 pts (4%) had BTH attributed to a CAC, 2 (1%) had BTH attributed to suboptimal C5 inhibition, and 2 (1%) had BTH of unknown cause in the crova arm. The ecu arm had 4 (6%), 3 (4%), and 2 (3%) pts with BTH attributed to a CAC, suboptimal C5 inhibition, and unknown cause, respectively. In the crova arm of COMMODORE 1, 2 pts (5%) had BTH attributed to a CAC, 1 pt (2%) had BTH attributed to suboptimal C5 inhibition, and 1 (2%) had BTH of unknown cause. In the ecu arm BTH occurring in 0 (0%), 3 (7%), and 1 (2%) pts were attributed to a CAC, suboptimal C5 inhibition, and unknown cause, respectively. Of all pts in the crova arms of COMMODORE 2 and 1, 8 (4%) had BTH attributed to a CAC, 3 (2%) had BTH attributed to suboptimal C5 inhibition (due to presence of anti-drug antibodies), 3 (2%) had BTH of unknown cause. In the ecu arms of both studies, 4 pts (4%) had BTH attributed to a CAC, 6 (5%) had BTH attributed to suboptimal C5 inhibition, and 3 (3%) had BTH of unknown cause. Incidence and categorization of BTH events were similar in both arms of COMMODORE 2 and 1. The majority of BTH cases occurring during the primary treatment periods in the crova arms were associated with a CAC while maintaining complete C5 inhibition. A similar trend was seen in the ecu arms. These results show that BTH was infrequent with crova and support the favorable benefit-risk profile of crova in both C5i-naive and C5i-experienced PNH pts.
Authors: R. Notaro, A. G. Kulasekararaj, J. Czyz, C. Flynn, G. Roncone Gastal, M. Hus, C. Lalayanni, E. Nur, P. Scheinberg, Y. Ueda, A. M. Vannucchi, M. Vidriales Vicente, I. Viigimaa, S. Buatois, A. C. Chang, S. Chebon, A. Röth
Institutions: Azienda Ospedaliero-Universitaria Careggi, King's College London, National Institute for Health and Care Research, King's College Hospital, Nicolaus Copernicus University, St. James's Hospital, Medical University of Lublin, G. Papanikolaou General Hospital, Sanquin, Amsterdam University Medical Centers, Beneficência Portuguesa de São Paulo, The University of Osaka, University of Florence, Complejo Hospitalario de Salamanca, North Estonia Medical Centre, Roche (Switzerland), Genentech, Essen University Hospital, University of Duisburg-Essen
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7093121348
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