Introduction
FibroGen completed the phase I single-dose, dose escalation studies as of July 2007. Multiple dose, dose escalation and phase II US studies are listed as ongoing.
Uses
In clinical development for the treatment of anemia of chronic inflammatory disease.
Pharmacodynamics
FG-4592 represents one of several next generation PHI that has been optimized for multiple pharmacokinetic and pharmacodynamic parameters related to erythropoiesis, including selective inhibition of HIF prolyl and asparaginyl hydroxylases, potency, iron utilization, and ADME. 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.
Mechanism of Action
FG-4592 is an orally active second generation HIF-PH inhibitor. 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.
Absorption
Orally active
Dosage
Patients not on erythropoiesis-stimulating agent treatment: For adults, the usual starting dose is 50 mg three times weekly. The recommended starting dose of roxadustat is 70 mg three times per week in patients weighing less than 100 kg and 100 mg three times per week in patients weighing 100 kg and over.
Patients switching from erythropoiesis-stimulating agents: For adults, the usual starting dose is 70 or 100mg three times weekly. The dosage thereafter should be adjusted according to the patient's condition.
Dose adjustment: When dose adjustments are required, increase or decrease the dose according to the "Dose increase/decrease table" and "stepwise Dose adjustment sequence" below. Once adjusted, maintain the dose level for ≥4 weeks. If the hemoglobin concentration increases rapidly (>2.0 g/dL) within 4 weeks of a dose increase, decrease the dose or suspend the treatment immediately.
The stepwise dose adjustments up or down should follow the sequence of the available doses: 20 mg-40 mg-50 mg-70 mg-100 mg-150 mg-200 mg-250 mg-300 mg-400 mg (only for CKD patients on dialysis).
Missed dose: When there is ≥ 24-hour interval until the next scheduled dosing time, take the missed dose immediately and follow the prescribed schedule for subsequent doses. If there is <24 hours until the next scheduled dosing time, skip the missed dose, and take the next dose as scheduled. Do not take 2 doses on the same day.
Method of administration: Roxadustat tablets are to be taken orally with or without food.
