FibroGen is already conducting multiple phase II clinical studies of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors that stimulate erythropoiesis for the treatment of anemia, including the company’s lead candidate, FG-2216, in the settings of chronic kidney disease and cancer.
Erythropoietic HIF-PH inhibitors increase the body’s endogenous production of erythropoietin, a hormone that stimulates the production of red blood cells, normalizes iron regulation, and reduces the adverse effects of inflammatory cytokines that otherwise suppress the formation of healthy red blood cells.
The sickle cell disease (SCD) research program at FibroGen seeks to combine the erythropoietic effects of HIF-PH inhibitors with the additional capacity to elevate fetal hemoglobin (HbF).
Work conducted under the phase II Small Business Innovation Research (SBIR) grant will focus on the identification of HIF-PH inhibitors that are effective in raising HbF either alone or in combination with hydroxyurea in a model of chronic anemia. From these studies, a HIF-PH inhibitor will be selected as a therapeutic candidate for clinical testing in patients with SCD.
The rationale underlying FibroGen’s HIF-PH inhibitor therapeutic program for SCD is guided by published reports demonstrating that the expression of HbF can be induced in primates, including humans, by exposure to hypoxic conditions.