Experimental Treatments

Cold agglutinin disease (CAD) is a rare autoimmune disorder in which autoantibodies known as cold agglutinins are produced when the body is exposed to cold temperatures. These cold agglutinins bind to red blood cells (RBCs) and destroy them, causing anemia.

Several treatment options are used in severe cases of CAD. New experimental therapies are being developed, such as those summarized below.

Bendamustine and rituximab combination

Rituximab monotherapy and rituximab-fludarabine combination therapy are used as first-line therapies for CAD. Recently, combination therapy of rituximab and bendamustine showed promising results in a Phase 2 clinical trial (NCT02689986).

The study recruited 45 patients, 71% of whom responded to treatment. Forty percent of these achieved a complete response while 31% achieved a partial response. Some of the patients previously treated with rituximab-fludarabine or rituximab alone also responded to the new rituximab-bendamustine combination, which was shown to be highly efficient and safe.


Eculizumab is a monoclonal antibody that binds to complement factor C5 and inhibits its activation, thereby preventing inflammation and red blood cell disintegration. The complement system consists of proteins called complement factors that interact with pathogens and help the body’s immune system to identify and destroy them.

In a Phase 2 clinical trial (NCT01303952), eculizumab was found to significantly reduce hemolysis (the breakdown of RBCs) and blood transfusion requirements in CAD patients.

BIVV009 (Sutimlimab)

BIVV009 (sutumlimab) is a monoclonal antibody that binds to C1s, an active upstream protein that is part of the classical complement pathway. BIVV009 blocks only this pathway, and does not affect the other two, namely the lectin and alternative pathways. In this way, it can preserve the complement system’s protective functions, such as fighting infections.

An ongoing Phase 1 clinical trial (NCT02502903) showed good tolerance of BIVV009 and significantly increased hemoglobin levels in CAD patients, reducing their need for blood transfusions.


Last updated: Aug. 11, 2019


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