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.A245154,L40114 This cold subtype accounts for approximately 15-25% of all AIHA and is more common in the elderly.A245159,L40114 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".^A245144 Hemolysis in patients with CAD is driven by complement activation, which initiates a cascade that ultimately leads to both intra- and extravascular hemolysis.^A245159 The most common presenting symptoms in patients with CAD are chronic anemia, acrocyanosis, and Raynaud phenomenon.^A245159

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.^A245159 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.^A245154 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.^A245144 It received FDA approval in February 2022, under the brand name Enjamyo (sutimlimab-jome), becoming the first approved therapy for patients with CAD.L40114,A245144 Sutimlimab was also approved by the European Commission in November 2022.^L44116