BACKGROUND: Cold agglutinin disease is a rare autoimmune hemolytic anemia 
characterized by hemolysis that is caused by activation of the classic 
complement pathway. Sutimlimab, a humanized monoclonal antibody, selectively 
targets the C1s protein, a C1 complex serine protease responsible for activating 
this pathway.
METHODS: We conducted a 26-week multicenter, open-label, single-group study to 
assess the efficacy and safety of intravenous sutimlimab in patients with cold 
agglutinin disease and a recent history of transfusion. The composite primary 
end point was a normalization of the hemoglobin level to 12 g or more per 
deciliter or an increase in the hemoglobin level of 2 g or more per deciliter 
from baseline, without red-cell transfusion or medications prohibited by the 
protocol.
RESULTS: A total of 24 patients were enrolled and received at least one dose of 
sutimlimab; 13 patients (54%) met the criteria for the composite primary end 
point. The least-squares mean increase in hemoglobin level was 2.6 g per 
deciliter at the time of treatment assessment (weeks 23, 25, and 26). A mean 
hemoglobin level of more than 11 g per deciliter was maintained in patients from 
week 3 through the end of the study period. The mean bilirubin levels normalized 
by week 3. A total of 17 patients (71%) did not receive a transfusion from week 
5 through week 26. Clinically meaningful reductions in fatigue were observed by 
week 1 and were maintained throughout the study. Activity in the classic 
complement pathway was rapidly inhibited, as assessed by a functional assay. 
Increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue 
coincided with inhibition of the classic complement pathway. At least one 
adverse event occurred during the treatment period in 22 patients (92%). Seven 
patients (29%) had at least one serious adverse event, none of which were 
determined by the investigators to be related to sutimlimab. No meningococcal 
infections occurred.
CONCLUSIONS: In patients with cold agglutinin disease who received sutimlimab, 
selective upstream inhibition of activity in the classic complement pathway 
rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue. 
(Funded by Sanofi; CARDINAL ClinicalTrials.gov number, NCT03347396.).