FibroGen, Inc., announced the publication of positive results from a Phase 2 clinical trial of roxadustat, its drug candidate for the treatment of anemia in patients with chronic kidney disease (CKD), and its intent to start a global Phase 3 testing program.
Results, detailed in the study “Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD,” published in Clinical Journal of the American Society of Nephrology, showed that roxadustat increased hemoglobin in CKD patients who were anemic, and reduced levels of serum hepcidin (a key regulator of iron entry into blood circulation). After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.
Anemia is a common complication of CKD, and associated with increased morbidity. Recombinant erythropoiesis–stimulating agents (ESAs) provide improved quality of life in both dialysis and non dialysis patient groups, and reduce red blood cell (RBC) transfusions. Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis by increasing endogenous erythropoietin, improving iron regulation and reducing hepcidin.
The multicenter, open label, randomized Phase 2b study assessed roxadustat for safety, efficacy, optimal dose, and dose frequency in 143 patients with nondialysis CKD, who had no previous treatment with erythropoiesis-stimulating agents. Patients were randomized into one of six cohorts (about 24 patients each) with varying roxadustat starting doses and frequencies (two and three times weekly), followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks.
Results revealed that 92 percent of the patients attained a hemoglobin response, defined as a hemoglobin increase of > 1.0 g/dl from baseline and hemoglobin of > 11.0 g/dl by the end of treatment (up to 16 weeks in 47 patients, and up to 24 weeks in 96 patients).
Participants in all cohorts who were treated with higher starting doses reached hemoglobin responses earlier.
Consistent with other published Phase 2 data, roxadustat increased hemoglobin independently of patients’ baseline iron repletion and inflammatory status (levels of C–reactive protein). Furthermore, the treatment decreased hepcidin and total cholesterol levels, and doses were well-tolerated.
“In this study, anemia correction was achieved under a range of treatment options including tiered weight as well as fixed-starting-dose strategies. Correction of anemia and maintenance of hemoglobin response were seen at different dose frequencies,” Robert Provenzano, MD, lead study author and chief of the Division of Nephrology, Hypertension & Transplantation, the director of Nephrology Research, and director of Acute Dialysis Services at St. John Hospital and Medical Center in Detroit, said in a press release. “Secondary analyses showing decreases in hepcidin and increased iron utilization, as well as reductions in total cholesterol levels, suggest roxadustat consistently affects these parameters.”
“This study shows that roxadustat can successfully correct anemia in chronic kidney disease patients who are not yet receiving dialysis,” added Thomas B. Neff, chief executive officer of FibroGen. “In exploring different dosing regimens, these results show that roxadustat achieved and maintained hemoglobin response at various dose frequencies, and provide continued evidence of roxadustat’s ability to achieve anemia correction without intravenous iron supplementation. FibroGen and our partners are encouraged by these results as we continue to advance the roxadustat global Phase 3 program and hope to provide a safer and more accessible option for patients.”