Phase III COMMODORE 1 Trial: 2-Year Efficacy and Safety of Crovalimab in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Switched from Ravulizumab

• Published in: Blood 2024-11, Vol.144, p.4078-4078
• Main Authors: Scheinberg, Phillip, Alzahrani, Hazza, Contento Gonzalo, Alejandro, Höglund, Martin, Kim, Jin Seok, Panse, Jens, Rose, Melissa J, Schubert, Jörg, Ueda, Yasutaka, Yap, Eng Soo, Buri, Muriel, Compagno, Nicolo', Gentile, Brittany, Sreckovic, Sasha, Kulasekararaj, Austin G.
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-200889

Introduction Crovalimab (crova; PiaSky®), a novel C5 inhibitor (C5i) allowing for maintenance subcutaneous (SC) injection every 4 wks (Q4W), was evaluated in the global, randomized, Phase III COMMODORE 1 and 2 trials (NCT04432584; NCT04434092). COMMODORE 2 demonstrated non-inferior efficacy of crova vs eculizumab (ecu) in C5i-naive patients (pts) (Röth Am J Hematol 2024). COMMODORE 1 showed similar safety and exploratory efficacy of crova vs ecu in randomized pts who switched from ecu (Scheinberg Am J Hematol 2024); this study also had a non-randomized arm with pts who switched from ravulizumab (ravu) to crova. Ravu, a C5i given IV every 8 wks, is becoming commonly used where available. Here, we report 2-y COMMODORE 1 data from the ravu switch cohort. Methods The ravu-pretreated cohort of the COMMODORE 1 non-randomized arm enrolled pts with PNH receiving ravu for ≥16 wks at study start and with lactate dehydrogenase (LDH) ≤2×upper limit of normal (ULN) at screening. All pts received a weight-based tiered dosing regimen of crova (loading doses and SC Q4W maintenance [self-administration was permitted]). The 24-wk primary treatment period was followed by an extension period. Safety was evaluated from baseline (BL) up to the clinical cutoff date (CCOD). Efficacy was assessed in the primary treatment period from BL to Wk (W)25 and in the extension period from W25-97. Efficacy endpoints included the proportion of pts with hemolysis control (LDH≤1.5×ULN) at each visit, and proportions of pts with transfusion avoidance (TA), breakthrough hemolysis (BTH), and hemoglobin (hb) stabilization; data were reported from BL to W25 and over consecutive 24-wk intervals in the extension from W25-49, W49-73, and W73-97. Pts who discontinued before the end of each 24-wk interval due to lack of efficacy were conservatively imputed to have had a transfusion, had a BTH event, and not had hb stabilization in that interval. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score was assessed at scheduled visits. Results 27 pts were enrolled, with a median age of 45 y (range, 13-70). 59% were male and 41% had a history of aplastic anemia. At BL, mean LDH was 1.01×ULN (SD, 0.19) and mean hb level was 108.5 g/L (SD, 19.9); mean packed red blood cell units transfused ≤1 y before screening was 0.81 (SD, 2.43). 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 an advers