C008 | PHASE III COMMODORE 2 AND 1 TRIALS: CHARACTERIZATION OF BREAKTHROUGH HEMOLYSIS EVENTS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH CROVALIMAB OR ECULIZUMAB

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.