Combined Safety Data for Sutimlimab in Cold Agglutinin Disease: A Post-Hoc Analysis of the Phase 3 Cardinal and Cadenza Studies

Background: Cold agglutinin disease (CAD) is a rare, chronic, autoimmune hemolytic anemia mediated by the classical complement pathway (CP).Sutimlimab is a first-in-class, humanized, monoclonal antibody that selectively inhibits C1s of the C1 complex, preventing CP activation and CP-mediated hemolysis. CARDINAL (NCT03347396) was an open-label, single-arm, Phase 3 study of sutimlimab in patients with CAD and recent history of transfusion; CADENZA (NCT03347422) was a randomized, double-blind, placebo-controlled, Phase 3 study of sutimlimab in patients with CAD and no recent history of transfusion. Both studies had a 26-week treatment period (Part A) followed by a long-term extension (Part B), reporting data up to 2 years after the last patient finished Part A of CARDINAL and up to 1 year after the last patient finished Part A of CADENZA. With long-term treatment in both studies, sutimlimab demonstrated sustained efficacy with improvements in hemolysis and anemia, sustained clinically meaningful improvements in quality of life, and it had a favorable safety profile. Aims: To report combined safety data from Part A and B of the Phase 3 CARDINAL and CADENZA studies in sutimlimab-treated patients with CAD. Methods: In CARDINAL Part A, patients received sutimlimab on Days 0 & 7, then biweekly until the end of Part B. In CADENZA Part A, patients received sutimlimab or placebo on Days 0 & 7, then biweekly; in Part B, patients continued to receive biweekly sutimlimab or switched from placebo to receive sutimlimab on Days 0 & 7, then biweekly. Data fromall enrolled patients who received at least 1 dose of sutimlimab in CARDINAL (N=24) and CADENZA (N=42), including a post-treatment follow-up 9 weeks after the last dose, were combined into the Safety Analysis Set. Endpoints for this analysis included the incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs). AESIs were selected based on a list of important identified risks and important potential risks for sutimlimab. Results: The Safety Analysis Set included 66 patients. At baseline, the median age was 69.5 years (range 46-88) and the majority (72.7%) were female, with a median duration since CAD diagnosis of 5.7 years (range 0-33). The median patient follow-up was 129.1 weeks (range 5-175). Sixty-four (97.0%) patients experienced ≥1 TEAE ( Table 1). Eighty-six TEAEs assessed as related to sutimlimab by the investigato