New England Journal of Medicine publishes roxadustat China phase III results for the treatment of anemia in chronic kidney disease patients receiving dialysis

FibroGen, Inc. announced the publication of clinical study results in the New England Journal of Medicine (NEJM)1 from the China Phase III trial of the efficacy and safety of roxadustat treatment for anemia in chronic kidney disease patients receiving dialysis and were receiving epoetin alfa prior to study participation . In this study, the primary efficacy endpoint was the mean change from the baseline in the hemoglobin level, averaged over Weeks 23 through 27. Roxadustat treatment resulted in a numerically greater mean increase in the hemoglobin level from baseline compared to epoetin alfa, and was non-inferior to epoetin alfa. Inflammation is a well-known cause of suppression of hemoglobin response in the erythropoiesis-stimulating agents (ESAs) in dialysis patients, reported in published literatures and was observed in the active comparator arm in this study. In contrast, inflammation, measured by elevated baseline C-reactive protein (CRP, a measure of inflammation) levels, did not appear to affect the hemoglobin response with roxadustat treatment in this study. Favorable changes in iron metabolism markers, such as transferrin, hepcidin, and serum iron, were noted with roxadustat as compared to epoetin alfa; this could result in reduced use of intravenous iron therapy and improved efficacy of oral iron supplementation with roxadustat. Anemia caused by CKD is associated with cardiovascular disease, hospitalization, cognitive impairment, and reduced quality of life, and has been shown consistently to be associated with an increased mortality risk2. Anemia becomes increasingly common among individuals with CKD as their kidney function declines, affecting nearly all CKD patients at the dialysis-eligible stage.

The trial (FGCL-4592-806) was a randomized open-label, active controlled study designed to compare the efficacy and safety of oral roxadustat to intravenous epoetin alfa (ESPO , Kyowa Hakko Kirin) in treatment of anemia patients receiving chronic dialysis who were previously on epoetin alfa treatment. In this China Phase III study, a total of 305 patients were randomized to roxadustat (n=204) and epoetin alfa (n=101) for a 26-week treatment period. The primary endpoint was the average change in hemoglobin from baseline to Week 23-27. The average baseline hemoglobin level was 10.4 g/dL. Notably, use of parenteral iron was restricted in these patients except as a rescue therapy. Roxadustat treatment resulted in a numerically greater mean hemoglobin change from baseline to Weeks 23-27 (0.7 g/dL+1.1) than epoetin alfa, (0.5 g/dL +1.0), and was non-inferior to EPO, in Full Analysis Set (FAS). Roxadustat-treated patients with elevated CRP had the similar hemoglobin response and dose requirement as in patients with normal CRP, and achieved higher Hb level than EPO-treated patients with elevated CRP level. EPO-treated patients with elevated CRP achieved lower hemoglobin response than those with normal CRP despite receiving higher doses of epoetin alfa.- % patients maintain Hb response (hemoglobin level not <1.0 g/dL below baseline value): 92.5% in both the roxadustat and EPO study arms.Roxadustat increased transferrin, maintained serum iron, and attenuated transferrin saturation (TSAT) decreases versus epoetin alfa. Roxadustat was associated with a reduction in hepcidin (by a mean of 30.2 ng/ml (95% CI (-64.8, -13.6)) compared to 2.3 ng/ml with epoetin alfa (95% CI -51.6, 6.2)), the central regulator of iron homeostasis. Of note, the previously reported mean hemoglobin level increase in the roxadustat arm higher than the comparator EPO arm (0.75g/dL vs. 0.46g/dL; p=0.037) was based on Per Protocol analysis per regulatory guidance.

The Phase III results importantly demonstrated roxadustat’s ability to correct anemia in patients with high levels of inflammation, a population known for poor response to ESA therapy. The adverse events observed during treatment were consistent with those expected in patients undergoing dialysis.

“Publication of the data from China Phase III anemia study in CKD patients on dialysis in the New England Journal of Medicine highlights the potential impact of roxadustat as the first oral anemia therapy, an effective therapy in maintaining hemoglobin levels in end-stage renal disease patients on dialysis, with or without comorbidity of inflammation,” said K. Peony Yu, M.D., Chief Medical Officer of FibroGen. “We are grateful for the opportunity to improve anemia care for a growing patient population as the number of patients requiring anemia therapy is expected to grow steadily as the CKD population and access to dialysis care continue to expand in China and globally.”

See- Chen, N, et al. Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis. New England Journal of Medicine. To be published July 24, 2019. https://www.nejm.org/doi/full/10.1056/NEJMoa1901713.