Approved Treatments for Cold Agglutinin Disease

Enjaymo (sutimlimab) is approved to treat hemolysis in patients with CAD. It works by selectively blocking the activity of C1 — a protein with a central role in the classical complement pathway, which is overly active in CAD, leading to hemolysis and anemia. It is the first approved therapy for this rare condition.

Erythropoietin (EPO) is a hormone produced by the kidneys that helps in the production of red blood cells. The administration of EPO could help the body produce more red blood cells to compensate for their loss in severe forms of CAD.  Excessive use of EPO, however, can lead to conditions associated with a rapid rise in hemoglobin concentrations, including cardiovascular events and blood clots.

Rituximab is used as a first-line treatment for CAD and is effective as a monotherapy in about half of all cases. It is an antibody that binds to the immune cells that produce autoantibodies. With fewer autoantibodies around to bind to red blood cells, there’s less clumping of these blood cells and fewer immune attacks.

Rituximab-fludarabine combination therapy has been recommended as a first-line treatment for CAD. Rituximab works by reducing the number of autoantibodies, while fludarabine inhibits DNA synthesis. Blocking DNA synthesis strongly affects those cells that rely on rapid cell division — like immune cells.