Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study

• Published in: Blood 2019-11, Vol.134 (Supplement_2), p.LBA-2-LBA-2
• Main Authors: Röth, Alexander, Barcellini, Wilma, D'Sa, Shirley, Miyakawa, Yoshitaka, Broome, Catherine M, Michel, Marc, Kuter, David J., Jilma, Bernd, Tvedt, Tor Henrik Anderson, Lin, Stella, Jiang, Xiaoyu, Reuter, Caroline, Hobbs, William, Berentsen, Sigbjørn
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-132490

Introduction CAD is a rare autoimmune hemolytic anemia with an estimated prevalence of 16 per 1 million. Hemolysis is driven by activation of the classical complement pathway (CP), resulting in erythrocyte opsonization with predominant extravascular destruction and ensuing anemia. Patients with CAD have an increased early mortality and risk of thromboembolism. There are no approved treatments. Sutimlimab (formerly BIVV009) is a first-in-class humanized monoclonal anti-C1s antibody that selectively inhibits the C1 complex of complement, preventing CP activation, while leaving the alternative and lectin pathways intact. The objective of the Cardinal study (NCT03347396) is to assess efficacy and safety of sutimlimab in adults with CAD who have a recent history of transfusion. Methods Cardinal is a pivotal Phase 3, open-label, single-arm, multicenter study of 26 weeks' duration (Part A) with an ongoing extension (Part B). Data is available from Part A. Patients with confirmed diagnosis of CAD were enrolled. Eligibility criteria included baseline hemoglobin (Hb) ≤10 g/dL, total bilirubin level above normal, and ≥1 blood transfusion in the prior 6 months. Sutimlimab was administered intravenously on Days 0 and 7, followed by biweekly infusions. Patients weighing