FG-4592 is an orally active second generation HIF-PH inhibitor in clinical development for the treatment of anemia of chronic inflammatory disease. Preclinical studies show that FG-4592 increases production of endogenous erythropoietin (EPO), increases iron mobilization and utilization, and overcomes the suppressive effects of inflammation on red blood cell production. FG-4592 represents one of several next generation HIF-PH inhibitors designed to selectively induce the expression of genes that mediate erythropoiesis for the treatment of anemia.

Read more about anemia.

Read more about selective HIF-mediated anemia therapy.

Clinical Development
Results of a Phase 1 dose-escalation study of FG-4592 in normal subjects reported at the American Society of Nephrology meeting in 2005 demonstrated that a single dose of FG-4592 induced increases in endogenous EPO significantly above baseline. A multi-dose study of FG-4592 is ongoing. No serious adverse events related to FG-4592 have been reported. Phase 2 studies are underway in the U.S.

Preclinical Studies

• FG-4592 can be used in a selective and controlled manner to induce HIF stabilization and to rapidly and reversibly stimulate EPO production and secretion.

• In a model of inflammation-induced anemia, FG-4592 dramatically reduced abnormally high levels of hepcidin back to normal levels and restored the natural balance in iron regulation. FG-4592 also alleviated microcytosis and hypochromia, typically associated with functional iron deficiency, and corrected anemia in this model.

• With a Small Business Innovation Research (SBIR) Phase II grant from the NIH, FG-4592 is being studied in preclinical models of Sickle Cell Disease (SCD). Preclinical studies so far have shown that certain HIF-PH inhibitors may have therapeutic potential in SCD by combining erythropoietic activity with an ability to disproportionately raise fetal hemoglobin. From this research, FG-4592 or another HIF-PH inhibitor will be nominated for clinical studies.