2-YEAR EFFICACY and SAFETY in PATIENTS (PTS) with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) WHO SELF-ADMINISTERED CROVALIMAB (CROVA) in the PHASE III RANDOMIZED COMMODORE 2 TRIAL.
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All Authors
Roth, A.
He, G.
Brodsky, A.
Chai-Adisaksopha, C.
Dumagay, T.
Gomez, R.
Hoglund, M.
Kelly, R.
Lee, J.
Nishimura, J.
LTHT Author
Kelly, Richard
LTHT Department
Oncology
Haematology
Haematology
Contributor Profession (Non Medical)
Publication Date
2025
Item Type
Conference Abstract
Language
Subject
Subject Headings
Abstract
Background Crova is a novel C5 inhibitor (C5i) that allows subcutaneous maintenance dosing Q4W, with the possibility for self-administration by the pt/caregiver or administration by a healthcare professional (HCP). Results from the COMMODORE 2 (NCT04434092) primary treatment (tx) period demonstrated non-inferior efficacy and comparable safety of crova vs eculizumab (ecu) in C5i-naive pts with PNH. In the extension period, crova was well tolerated and pts maintained disease control over a 2-year median follow-up, supporting crova's long-term favorable benefit-risk profile. Aims To assess long-term efficacy and safety of crova in pts with self-administered vs HCP-administered crova in COMMODORE 2. Methods C5i-naive pts were randomized 2:1 to crova (Arm A; weight-based tiered dosing) or ecu (Arm B; 900 mg Q2W) for the primary tx period (Week [W]1-24). Arm A pts continued crova and Arm B pts switched from ecu to crova (Arm B switch) if continuing in the extension period (Arm A W25-97 corresponds to Arm B switch post-switch W1-73). Crova self-administration was permitted from W9, after pt training and confirmation of proficiency by an HCP. Long-term data were collected from pts who received crova up to W97. Outcomes included hemolysis control (lactate dehydrogenase [LDH] <=1.5xupper limit of normal [ULN]) at each visit, transfusion avoidance (TA; pts free of packed red blood cell transfusion) and hemoglobin (Hb) stabilization (<2 g/dL Hb decrease from baseline in the absence of transfusion) over consecutive 24-week intervals, pharmacokinetics, pharmacodynamics, tx preference in Arm B switch, and safety. Data were analyzed in subgroups of pts by number of self-administered doses (0 vs <median [18 in Arm A; 16 in Arm B switch] vs >=median). Results At the clinical cutoff, 64% (86/135) of pts in Arm A and 72% (49/68) in Arm B switch had >=1 crova self-administration (range 1-37 and 3-30 doses, respectively); no medication errors occurred. Disease control was maintained and crova was well tolerated across subgroups (Table); no fatal adverse events (AEs) were deemed to be tx related and only one pt per arm stopped tx due to AEs. Crova exposure was similar across subgroups, with mean serum concentrations from 207-235, 217- 261, and 210-242 mug/mL in pts with 0, <18, and >=18 self-administered doses in Arm A from W25-97 and 218-354, 183- 339, and 228-380 mug/mL in pts with 0, <16, and >=16 self-administered doses in Arm B switch from post-switch W1-73. Free C5 (<0.0001 g/L [the target threshold] at most visits for all pts) and CH50 (5-7 U/mL in Arm A and 5-9 U/mL in Arm B switch) were also similar across subgroups. In Arm B switch pts who responded to a questionnaire, 80% (12/15) with 0 self-administered doses preferred crova over ecu vs 78% (14/18) with <16, and 91% (21/23) with >=16; 13% (2/15), 11% (2/18), and 0% (0/23) preferred ecu over crova, and 7% (1/15), 11% (2/18), and 9% (2/23) had no preference, respectively. Among pts with >=16 self-administered doses, 71% (15/21) preferred crova because it was an easier way to give tx; other reasons for preferring crova given by >=50% of pts in any self-administration subgroup were fewer tx-associated hospital visits and shorter tx administration time. Summary/Conclusion In COMMODORE 2, crova was well tolerated and maintained disease control over a 2-year median follow-up in C5i-naive pts with PNH, regardless of who administered the drug. These results further support the long-term favorable benefit-risk profile of crova and the feasibility of crova self-administration.
Journal
HemaSphere