Sutimlimab

Cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia (AIHA) in which autoantibodies directed against red blood cell surface antigens cause hemolysis at low (3-4°C) temperatures. This cold subtype accounts for approximately 15-25% of all AIHA and is more common in the elderly. In approximately 90% of cases, patients develop immunoglobulin M (IgM) autoantibodies towards the I antigen on erythrocytes - these antibodies react optimally at 4°C and are therefore referred to as "cold agglutinin". Hemolysis in patients with CAD is driven by complement activation, which initiates a cascade that ultimately leads to both intra- and extravascular hemolysis. The most common presenting symptoms in patients with CAD are chronic anemia, acrocyanosis, and Raynaud phenomenon.

Treatment options for patients with CAD are limited. In addition to non-pharmacological strategies, such as counseling patients to keep warm and the use of red blood cell transfusions, approximately 70% of patients require pharmacological treatment. Pharmacologic strategies have included the targeting of B-cells with agents like rituximab, as well as targeting of the complement system with drugs like eculizumab, an anti-C5 mAb, and pegcetacoplan, a novel inhibitor of C3. Notably, none of these agents are approved for use in the treatment of CAD.

Sutimlimab is a first-in-class humanized monoclonal antibody targeted at complement subunit C1s, which is responsible for activating the classic complement pathway. It received FDA approval in February 2022, under the brand name Enjamyo (sutimlimab-jome), becoming the first approved therapy for patients with CAD. Sutimlimab was also approved by the European Commission in November 2022.