DP056 | PHASE III COMMODORE-1 TRIAL: 2-YEAR EFFICACY AND SAFETY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO SWITCHED FROM RAVULIZUMAB

Crovalimab (crova) is a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) injection every 4 wks (Q4W). COMMODORE 1 study demonstrated the safety and exploratory efficacy of crova in randomized pts who switched from eculizumab (ecu); this study also had a non-randomized arm with pts who switched from ravulizumab (ravu) to crova. We report 2-y COMMODORE 1 data of this last arm. The ravu-pretreated cohort enrolled pts with PNH receiving ravu for ≥16 wks and with LDH ≤2×ULN at screening. 27 pts were enrolled [median age of 45 y (13-70)]. 59% were male and 41% had a history of aplastic anemia. At baseline (BL), mean LDH was 1.01×ULN; mean hb level was 108.5 g/L; mean packed red blood cell units transfused ≤1 y before screening was 0.81. 21 of 27 pts completed 24 wks of crova and entered the extension period. 6 pts discontinued the trial before W25; 5 due to pt withdrawal and 1 due to sepsis. No pts discontinued due to lack of efficacy. All pts who entered the extension period continued crova. Median treatment duration was 96.1 wks. The rate of pts with LDH≤1.5×ULN at each visit was 81-100% from BL-W25 and 95-100% from W25-97. From BL-W25, 70% of pts (19/27) achieved transfusion avoidance and 63% (17/27) achieved hb stabilization. From W25-97, 88-95% of pts achieved TA and 88-93% achieved hb stabilization. BTH occurred in 26% (7/27) of pts from BL-W25 and 0-10% of pts (2 pts) from W25-97; majority were singular events due to a concurrent complement-activating condition. Mean FACIT-Fatigue scores ranged from 31.2-37.0 from BL-W25 and 35.2-37.2 from W25-97. Incidence of AEs per 100 pt years (95% CI) was 549.0 for all AEs, 71.4 for Grade ≥3 AEs . No deaths occurred. TICRs occurred in 33% of pts (9/27) with rash, arthralgia, and myalgia but no renal manifestations. Median time to 1st TICR onset was 2.0 wks (range, 1.3-4.3) with a median duration of 1.7 wks (0.6-11.9). TICRs were mild/moderate, with no life-threatening or fatal events. All TICRs resolved with no change in crova treatment. No meningococcal infections occurred. Most pts who switched from ravu to crova maintained hemolysis control through W25, consistent with COMMODORE 1 data. Most pts maintained disease control during the extension period. These exploratory results should be interpreted with caution due to small sample size and inherent variability of underlying disease. No evidence suggests that safety/efficacy profile of crova differs between pts who switched from ravu or from ecu.