The following article features coverage from the American Society of Hematology 2021 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

Sutimlimab was well tolerated and efficacious, halting hemolysis, increasing hemoglobin, and improving quality of life in patients with cold agglutinin disease (CAD), according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

The findings come from Part A of the CADENZA study ( Identifier: NCT03347422), a 26-week (Part A) randomized, double-blind, placebo-controlled phase 3 study with open-label extension (Part B) to evaluated the efficacy and safety of sutimlimab in patients with CAD without recent transfusion history.

The study included patients with CAD with a baseline hemoglobin of ≤10 g/dL, bilirubin above normal, transfusion independence, and ≥1 CAD symptom. Patients were randomized (1:1) to receive sutimlimab (n=22) or placebo (n=20) on days 0 and 7, followed by biweekly infusions. The composite primary endpoint was the proportion of patients with hemoglobin increase ≥1.5 g/dL at the time of treatment assessment (mean, weeks 23, 25, and 26) and avoidance of transfusion and CAD therapy (weeks 5-26). Key secondary endpoints included markers of hemolysis, quality of life assessed via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) tool, and pharmacodynamic outcomes.

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The composite primary endpoint was met by 73% and 15% of patients in the sutimlimab and placebo arm, respectively (odds ratio [OR], 15.9; 95% CI, 2.9-88.0; P <.001). At the treatment assessment timepoint, 73% of patients treated with sutimlimab had an increased hemoglobin ≥2 g/dL from baseline compared with 10% of patients in the placebo arm. From weeks 5-26, 5% of patients in the sutimlimab arm and 20% patients in the placebo arm received transfusions.

Sutimlimab increased mean hemoglobin and FACIT-Fatigue and normalized mean bilirubin by week 1; these changes were sustained to the treatment assessment timepoint. At the treatment assessment timepoint, the least squares mean difference in hemoglobin and FACIT-Fatigue between sutimlimab and placebo was 2.6 g/dL (P <.001) and 8.9 points (P <.001), respectively. No improvements were observed with placebo.

From baseline to the treatment assessment time, treatment with sutimlimab led to improvements in additional hemolysis markers, including decreased lactate dehydrogenase levels and reticulocyte counts, and increased haptoglobin levels; no improvements were seen with placebo.

Treatment-emergent adverse events (TEAEs) occurred in 96% and 100% of patients in the sutimlimab and placebo arms, respectively. Hypertension (22.7% vs 0%), headache (22.7% vs 0%), Raynaud’s phenomenon (18.2% vs 0%), rhinitis (18.2% vs 0%), and acrocyanosis (13.6% vs 0%) were reported more frequently in the sutimlimab arm than in the placebo arm. Serious TEAEs occurred in 14% and 5% of patients in the sutimlimab and placebo arms, respectively. Cerebral venous thrombosis was assessed as sutimlimab-related by the investigator for 1 serious TEAE. No deaths occurred.

“Collectively the CADENZA and the CARDINAL phase 3 data demonstrate that sutimlimab has the potential to be an important advancement in the treatment of hemolysis in patients with CAD,” said Alexander Roeth, MD, of University Hospital Essen in Essen, Germany, who presented the study.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

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Roeth A, Berentsen S, Wilma Barcellini W, et al. 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. Presented at ASH 2021; December 11-14, 2021. Abstract 349.