The monoclonal antibody sutimlimab is well-tolerated and improved the quality of life in patients with cold agglutinin disease (CAD).

The results from the placebo-controlled trial CADENZA (NCT03347422) and the single-arm CARDINAL study (NCT03347396) will be presented at the 63rd American Society of Hematology Annual Meeting & Exposition (ASH), being held December 11-14, 2021.

Most (73%) patients receiving sutimlimab met the composite primary endpoint criteria (ie, hemoglobin [Hb] increase ≥1.5 g/dL) at the treatment assessment timepoint (TAT, mean of weeks 23, 25, and 26). In the placebo arm, only 15% met these criteria. One patient in the treatment arm and 4 in the placebo arm received transfusions during weeks 5 to 26.

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One week of treatment with sutimlimab increased mean Hb and Functional Assessment of Chronic Illness Therapy-Fatigue scores, with improvements being sustained to the TAT. These improvements were not observed in the PBO arm.

In addition, sutimlimab decreased lactate dehydrogenase levels and reticulocyte counts, improved hemolysis markers, and increased haptoglobin levels. The incidence of solicited symptomatic anemia symptoms in patients receiving sutimlimab was reduced from baseline to week 26. On the other hand, the incidence of weakness and shortness of breath was reduced in the placebo arm.

“In the sutimlimab arm, improvements in anemia, hemolysis, and fatigue coincided with normalized C4 levels and near-complete classical pathway inhibition, with reductions in classical pathway activity (Wieslab) and CH50 levels,” the authors explained. The results also suggest that the levels and prophagocytic functions of the complement component 1q are not affected by treatment with sutimlimab.

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All patients in the placebo arm and almost all (96%) in the sutimlimab arm reported ≥1 treatment-emergent adverse events (TEAEs). These included ≥1 serious TEAE in 3 patients receiving sutimlimab and 1 patient in the PBO arm. Raynaud’s phenomenon, rhinitis, hypertension, headache, and acrocyanosis were mainly observed in the sutimlimab arm rather than in the PBO arm.

The study reported no deaths, meningococcal infections, hypersensitivity reactions or anaphylaxis, TEAEs suggestive of the development/worsening of autoimmune disease, or systemic lupus erythematosus in response to sutimlimab treatment. Serious infections and 1 serious TEAE of cerebral venous thrombosis were reported.

Three patients in the sutimlimab arm discontinued treatment from the 26-week (part A) study due to TEAEs. CADENZA has an open-label extension (part B) to assess sutimlimab in patients with CAD without recent transfusion history.


Roeth A, Berentsen S, Barcellini W, et al. 349 Inhibition of complement C1s by sutimlimab in patients with cold agglutinin disease (CAD): efficacy and safety results from the randomized, placebo-controlled phase 3 CADENZA study. Oral presentation presented at: 63rd American Society of Hematology Annual Meeting & Exposition: December 11-14, 2021; Atlanta, Georgia.

A study to assess the efficacy and safety of BIVV009 (sutimlimab) in participants with primary cold agglutinin disease without a recent history of blood transfusion (CADENZA). November 20, 2017. Updated September 3, 2020. Accessed November 16, 2021.

A study to assess the efficacy and safety of BIVV009 (sutimlimab) in participants with primary cold agglutinin disease who have a recent history of blood transfusion (CARDINAL study). November 20, 2017. Updated October 5, 2021. Accessed November 16, 2021.