B06 | PHASE III RANDOMIZED COMMODORE 1 TRIAL: 2-YEAR SAFETY AND EFFICACY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO SWITCHED FROM ECULIZUMAB

Crovalimab (crova) is a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) injection every 4 wks (Q4W). Results from the 24-wk primary treatment period of randomized Phase III COMMODORE 1 trial showed that crova was well tolerated and had similar efficacy in patients (pts) who switched from eculizumab (ecu) to crova vs pts who continued ecu. Here, we report 2-y COMMODORE 1 data. PNH pts receiving ecu for ≥24 wks at study start with LDH ≤1.5×ULN were randomized 1:1 to switch to crova (Arm A) or continue ecu (Arm B) for a 24-wk primary treatment period. After primary treatment, pts in Arm A continued crova, and pts in Arm B switched from ecu to crova if continuing in the extension period (Arm B switch). Long-term efficacy was evaluated up to W97 in the extension period in each arm. Efficacy endpoints were % of pts with hemolysis control (LDH≤1.5×ULN) at each visit from W25-97, % of pts with transfusion avoidance (TA), breakthrough hemolysis (BTH), hemoglobin (hb) stabilization. All 44 pts from Arm A (crova) continued crova and 40/42 pts from Arm B (ecu) switched to crova in the extension period after W25. 42 pts in Arm A and 32 in Arm B switch were receiving crova. Median treatment duration was 106.2 wks. Across Arm A and Arm B switch, 84 pts (173.4 pt years [PY]) were evaluated for the long-term safety of crova. Incidence of adverse events (AEs) per 100 PY was 362.8 for all AEs, 50.8 for treatment-related AEs, 45.6 for Grade ≥3 AEs and 29.4 for serious AEs. The % of fatal AEs was 0.58 per 100 PY; the 1 death was unrelated to treatment. TICRs occurred in 18% of pts (15/84). TICRs signs and symptoms were mainly skin and joint abnormalities (rash and arthralgia) with no renal manifestations, no life-threatening or fatal events and resolved with no change in crova treatment. No meningococcal infections occurred. Mean normalized LDH was maintained at ≤1.5xULN in both arms, with 77-94% of pts in Arm A and 89%-100% in Arm B switch having LDH ≤1.5×ULN at each visit from W25-97. TA was achieved by 76%-84% of pts in Arm A and 75%-81% in Arm B switch; hb stabilization was achieved in 68-73% and 60-70% of pts, respectively. Proportion of pts with a BTH event remained low and generally stable (7-11% in Arm A and 3%-18% in Arm B switch). In COMMODORE 1, crova was well tolerated and disease control was maintained over a 2-y median treatment duration in pts who switched from ecu to crova, showing a durable and consistent efficacy profile.