American Society of Hematology

Phase III Trial Finds Sutimlimab Effective Against Cold Agglutinin Disease

Drug could change treatment practices for rare disorder 

Published on: December 10, 2019

(Orlando, FL, Dec. 10, 2019) — Patients with cold agglutinin disease (CAD) had improved hemoglobin levels, required fewer blood transfusions, and felt significantly less fatigued after receiving the experimental drug sutimlimab for 26 weeks in a phase III clinical trial presented today during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando.  

CAD is a rare autoimmune disease in which a person’s immune system attacks and destroys red blood cells. People with CAD suffer severe anemia and fatigue and face an increased risk for dangerous blood clots and early death. The disease typically develops later in life, with most patients diagnosed in their 60s or 70s. 

There are currently no approved treatments for CAD. Sutimlimab is a monoclonal antibody designed to block C1s proteins from activating the classical complement pathway, the part of the immune system that is overactive in people with CAD. The new study sought to evaluate whether blocking C1s with sutimlimab could help patients with CAD retain more of their red blood cells and reduce the disease’s symptoms and complications. 

“In our study, sutimlimab rapidly and effectively stopped the underlying hemolysis, or destruction, of red blood cells in CAD patients and had a marked improvement on how patients experience fatigue,” said lead study author Alexander Röth, MD, University of Duisburg-Essen, Germany. “I think we have finally turned the corner with research related to CAD and now have the potential to offer a targeted therapy for these patients, pending health authority approvals.” 

The researchers enrolled 24 patients who averaged 71 years old. Twenty-two patients completed the study. At the start of the trial, all patients had evidence of active CAD, including hemoglobin levels of less than or equal to 10 g/dL, above-normal total bilirubin, and at least one blood transfusion in the prior six months. Patients received sutimlimab via intravenous infusion for 26 weeks, and their CAD symptoms were assessed at weeks 23, 25, and 26. 

The trial’s primary efficacy endpoint was response to sutimlimab measured as a composite of hemoglobin increase of two or greater, or a total hemoglobin level of 12 or higher, along with avoidance of a blood transfusion from weeks 5-26. The researchers also tracked changes in bilirubin levels and quality of life, assessed using the FACIT-Fatigue score. 

The trial met its primary endpoint, with hemoglobin improving rapidly after patients received their first dose of sutimlimab. By week three, most patients had hemoglobin above 11 g/dL and normalized total bilirubin. Quality of life scores improved within a week and remained stable through week 26. 

“We were very thrilled to see that several clinical efficacy outcome measures for bilirubin, hemoglobin, and FACIT-Fatigue score were closely aligned for their timing and durability of response with the kinetics of inhibition of the classical complement pathway,” said Dr. Röth. “This really illustrates that targeting C1s in the classical complement pathway can have a meaningful impact on hemolysis, anemia, and fatigue, which are important clinical features of CAD.”

Almost all patients (92%) experienced at least one adverse event during the course of the study, and 29% experienced a serious adverse event. However, most of these events were related to surgical procedures or pre-existing medical conditions and were not found to be related to sutimlimab. Adverse events that were determined to be related to sutimlimab, all of which were considered non-serious, included swelling, increased blood pressure, and runny nose. All patients who completed the trial elected to continue to participate in a second phase that will assess longer-term outcomes from continued use of sutimlimab.  

Researchers noted that the study did not include a placebo control group and was limited by its small size, a common limitation for studies of rare diseases. A separate, ongoing study, involving a placebo control and patients without a recent history of blood transfusions, could help determine sutimlimab’s potential benefits or risks in a broader patient population. In addition, Dr. Röth noted that a planned CAD patient registry should help researchers better understand the disease and its complications. 

The study authors and press program moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on VTE, sickle cell disease, inclusive medicine, and CAR-T and beyond. For the complete annual meeting program and abstracts, visit Follow @ASH_hematology and #ASH19 on Twitter and like ASH on Facebook for the most up-to-date information about the 2019 ASH Annual Meeting.

The American Society of Hematology (ASH) ( is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (, the most cited peer-reviewed publication in the field, which is available weekly in print and online. In 2016, ASH launched Blood Advances (, an online, peer-reviewed open-access journal.


Adam Silverstein, FleishmanHillard 

Leah Enser, ASH 

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