The phase III ARCADE study of darbepoetin alfa (Aranesp, Amgen) has met its primary endpoint of reducing the incidence of red blood cell transfusions in anemic patients with low- or intermediate-risk myelodysplastic syndrome (MDS) at the end of the 25-week study period. Darbepoetin also significantly improved the erythroid response, a key measure of the formation of new red blood cells.
Darbepoetin alfa is an erythropoiesis-stimulating protein that is produced in Chinese hamster ovary cells by recombinant DNA technology. It stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.
The ARCADE trial was a randomized, double-blind, placebo-controlled study evaluating darbepoetin in 146 patients with low- or intermediate-1 risk MDS who had not received erythropoiesis-stimulating agents or biologic response modifiers. During a 24-week period, patients received either darbepoetin 500 mcg (n = 97) or placebo (n = 49) every three weeks. At week 25, when the primary and key secondary endpoints were assessed, patients could enter a 48-week active treatment period in which all participants crossed over to receive darbepoetin, with dose escalation allowed beginning on week 31. Treatment continued until week 72 or 73, and long-term follow-up is continuing to occur every 26 weeks, for a minimum of three years.
Darbepoetin alfa is indicated for the treatment of anemia due to chronic kidney disease, including patients on dialysis and patients not on dialysis. It is also indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation there is a minimum of two additional months of planned chemotherapy.
MDS is among the most common types of bone marrow failure syndromes in adults. The disease occurs when immature blood cells do not mature in the bone marrow. Patients with MDS have fewer healthy white blood cells, red blood cells, and platelets, and are at risk of infection, anemia, or bleeding. Current treatments for MDS include blood transfusions, chemotherapy, and stem cell transplants.