Inhibition of Complement C1s By Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Efficacy and Safety Results from the Randomized, Placebo-Controlled Phase 3 CADENZA Study

Background: CAD is a rare autoimmune hemolytic anemia mediated by classical complement pathway activation. Sutimlimab, a first-in-class humanized monoclonal anti-C1s IgG antibody, selectively inhibited the classical pathway, halted hemolysis, and improved hemoglobin (Hb) and quality of life (QOL) in patients with CAD and recent transfusion history (single-arm CARDINAL study [NCT03347396]). CADENZA (NCT03347422) is a 26-week (Part A) randomized, double-blind, placebo (PBO)-controlled Phase 3 study with open-label extension (Part B) to assess sutimlimab in patients with CAD without recent transfusion history. Aim: To report efficacy and safety results from CADENZA Part A. Methods: Patients with confirmed CAD diagnosis, baseline (BL) Hb ≤10 g/dL, bilirubin above normal, transfusion independence, and ≥1 CAD symptom were enrolled. Patients were randomized 1:1 to receive sutimlimab (body weight