Interim Results From CARDINAL Trial Show Sutimlimab Effective in CAD

Patients with cold agglutinin disease (CAD) had durable responses at week 53, and no new safety signals were reported.

Newly released data from the CARDINAL study of sutimlimab (Enjaymo) for the treatment of cold agglutinin disease (CAD) show the C1s inhibitor has durable results at 1 year.

The new interim results were published as a letter to the editor in Haematologica.

CAD is a type of autoimmune hemolytic anemia in which patients experience chronic hemolysis brought about by the activation of the classical component pathway, said corresponding author Alexander Röth, PhD, of the University of Duisburg-Essen, in Germany, and colleagues.

At the time of the study's launch there were no approved therapies for CAD, although the FDA has since approved sutimlimab for adults with the disease.

Rituximab (Rituxan) can produce a partial response in some patients by depleting B cells, though Röth and colleagues said relapse is common. Adding cytotoxic agents can increase response rates, but also increases toxicity.

“Thus, an alternative treatment that is non-cytotoxic, rapid, and durable in controlling classical complement-mediated hemolysis and its clinical manifestations in CAD patients is needed,” the authors said.

Sutimlimab is a humanized monoclonal antibody targeting the complement-specific serine protease C1s, which activates the classical component pathway, leading to hemolysis. The ongoing CARDINAL study is a prospective, single-arm, open-label trial made up of 2 parts: a 26-week treatment period (Part A) and an extension period (Part B) slated to last until 2 years after the final patient completed the first portion. The new data represent the findings halfway through the second part of the study.

Out of 24 patients who enrolled in the first part of the study, 22 completed the treatment and entered the second part. The study population was mostly female (62.5%) and aged 65 or older (79.2%). Patients received sutimlimab intravenously on days 0 and 7 and then every 2 weeks thereafter.

At baseline, the patients in the study had reduced mean hemoglobin (8.6 g/dL) and elevated mean bilirubin (53.3 µmol/L). Both metrics had improved after the first dose. At 53 weeks, Röth and colleagues reported, the subjects had a sustained hemoglobin increase of at least 2 g/dL from week 3 onward, and 11 of the 22 patients had a normalized hemoglobin level of >12 g/dL by that point. Bilirubin levels dropped quickly. By week 53, 14 of the 22 patients had normalized bilirubin levels (<20.5 µmol/L), with a mean change of bilirubin from baseline of -35.3 µmol/L. Seventeen patients remained transfusion-free during Part A of the trial, and 19 were transfusion free during Part B (weeks 27-53).

The data also showed a sustained improvement in fatigue scores, and a durable decline in classical component pathway activity.

Treatment-emergent adverse events (TEAE) were reported in all 24 patients who enrolled in the trial, and 9 patients had one or more TEAE that was deemed to be related to sutimlimab. Acrocyanosis/cyanosis and infusion-related reactions were the most common therapy-related events, and diarrhea and nasopharyngitis were the most common overall TEAEs. Though 2 patients discontinued treatment during the 53 weeks, the authors said those discontinuations were for reasons unrelated to the study treatment.

“In summary, 1-year interim results of the ongoing CARDINAL study demonstrate continued inhibition of the classical component pathway at C1s with sutimlimab and sustained treatment effects in CAD,” Röth and colleagues concluded.

The authors said the lack of new safety signals reinforce the “positive risk-benefit” profile of the therapy, and the durability of the results suggest the therapy can be effective over the long term.


Roth A, Barcellini W, D'Sa S, et al. Complement C1s inhibition with sutimlimab results in durable response in cold agglutinin disease: CARDINAL study 1-year interim follow-up results. Haematologica. 2022;107(7):1698-1702. doi:10.3324/haematol.2021.279812