Sutimlimab, a first-in-class monoclonal antibody, may be an effective treatment option for patients with cold agglutinin disease (CAD), according to the results of a phase 3 trial published in Blood. There was, furthermore, evidence that sutimlimab reduced hemolysis and anemia without a need for transfusion.

CAD, a rare autoimmune disease, is defined by chronic hemolysis and hemolytic anemia. Patients without signs of malignancy who show symptoms of CAD may have the disease detected in either blood or bone marrow samples.

CAD is characterized by activation of the classical complement pathway; previous research has suggested that the antigen-IgM antibody complex is a trigger of the classical complement pathway. Anemia, hemolysis, fatigue, and jaundice are all known symptoms of CAD, each of which is complement-mediated.

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Patients with CAD, furthermore, face a limited number of treatment options, and prior to the approval of sutimlimab — an antibody designed to target C1s — there was no therapy specifically approved in the United States for this disease. For the randomized phase 3 CADENZA trial ( Identifier: NCT03347422), researchers evaluated whether sutimlimab has superior safety and efficacy compared with placebo among patients with CAD.

Overall, 42 patients were included in this study, among whom 22 were randomly assigned to the sutimlimab group and 20 were assigned to the placebo group. In the experimental and placebo groups, the median ages at baseline were 64 and 69 years, respectively, 77.3% and 80% of patients were female sex, and 54.5% and 60% of patients had received prior rituximab.

Analysis suggested that the study’s composite primary endpoint — a hemoglobin increase of at least 1.5 g/dL, transfusion avoidance, and study-prohibited anti-CAD treatment — was met by 73% of patients in the experimental group vs 15% of patients in the placebo group (odds ratio, 15.9; P <.001).

Patients randomly assigned to receive sutimlimab also had improvements in mean hemoglobin levels, fatigue, and bilirubin levels. The authors suggested that the noted improvements correlated with almost complete inhibition of the classical complement pathway.

In the sutimlimab and placebo groups, 95.5% and 100% of patients had an adverse event; 13.6% of patients in the sutimlimab group discontinued treatment because of a treatment-related event.

“These data show that targeting the classical complement pathway at C1s represents a new, effective therapeutic approach for CAD management, independent of transfusion status, with treatment responses as early as week 1 and a favorable tolerability profile,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Röth A, Berentsen S, Barcellini W, et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022;140(9):980-991. doi:10.1182/blood.2021014955