Inhibition of complement C1s with sutimlimab may rapidly and effectively prevent further hemolysis in patients with cold agglutinin disease, according to research published in Blood. In addition, sutimlimab induced clinically meaningful increases in hemoglobin levels even in patients with multiple previous lines of therapy, eliminating the need for transfusions.
Sutimlimab, a humanized anti-C1s immunoglobulin G4 monoclonal antibody, already has orphan drug designation in the United States and the European Union. In a phase 1b study, 10 patients with cold agglutinin disease received a 10 mg/kg test dose of sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later. Patients received 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication and no serious treatment-related adverse events occurred.
Seven patients experienced a hemoglobin increase of at least 2 g/dL over the course of the treatment. Overall, hemoglobin levels increased by a median of 1.6 g/dL within the first week and by a median of 3.9 g/dL within 6 weeks (P =.005). Sutimlimab rapidly inhibited extravascular hemolysis and normalized bilirubin levels within 24 hours for most patients. Within 7 days, haptoglobin levels were normalized in 4 patients.
All 6 previously transfused patients became transfusion free during treatment. The researchers concluded that the safety data are encouraging, but the findings must be interpreted cautiously in light of the limited duration of the trial.
1. Jager U, D’Sa S, Schörgenhofer C, et al. Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial [published online December 17, 2018]. Blood. doi: 10.1182/blood-2018-06-856930