A new study has demonstrated that sutimlimab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody, was effective at halting hemolysis in recently transfused patients with cold agglutinin disease (CAD). The study, published in Blood, derived from the CADENZA study, a placebo-controlled trial of sutimlimab in patients with CAD from the CARDINAL study.

“Sutimlimab has a novel and targeted mechanism of action that specifically addresses the underlying cause of chronic hemolytic anemia in CAD,” the authors wrote. “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.”

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Forty-two patients with CAD were randomized to receive either sutimlimab or placebo in the study. The primary endpoint was efficacy in terms of an increase in hemoglobin from a baseline of ≥1.5 g/dL at weeks 23, 25, and 26, no need for blood transfusions between weeks 5 and 26, and the avoidance of protocol-prohibited medications for CAD between weeks 5 and 26.

The results showed normalization of mean hemoglobin levels and hemolysis markers as well as significant improvements in fatigue in patients without a history of recent blood transfusion. The response developed within 1 to 3 weeks and lasted over 26 weeks. Bilirubin levels were also normalized. The placebo had no effect on these parameters.

Sutimlimab selectively inhibits the classical complement pathway at C1s, and the authors note that the results of this study correlate with almost complete inhibition of classical complement pathway activity in the sutimlimab patient group.


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. Published online June 10, 2022. doi:10.1182/blood.2021014955