Date: 2016-02-16
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results int he American Journal of Kidney Disease
Company: FibroGen (USA - CA)
Product: roxadustat
Action
mechanism: enzyme inhibitor/hypoxia inducible factor (HIF) prolyl hydroxylase inhibitor. Roxadustat (FG-4592) is an orally administered small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase activity, in development for the treatment of anemia in patients with chronic kidney disease (CKD). HIF is a protein transcription factor that induces the natural physiological response to conditions of low oxygen, "turning on" erythropoiesis and other protective pathways.
Disease: anemia associated with chronic kidney disease (CKD)
Therapeutic area: Kidney diseases - Renal diseases
Country:
Trial
details: The study was a randomized, open-label, active-comparator study in dialysis patients who previously had hemoglobin (Hb) levels maintained with epoetin alfa. This study was conducted in 144 patients who received roxadustat or epoetin alfa for a period of six weeks in part one or 19 weeks in part two. Eligible patients were aged 18 to 75 years and receiving maintenance hemodialysis thrice weekly for four or more months. Hb levels were 9.0 to 13.5 g/dL for eight weeks, and patients had stable epoetin alfa dosages of < 450 U/kg/wk for four weeks prior to randomization. Roxadustat was dosed orally three times weekly. Initial dosing cohorts ranged between 1.0 – 2.0 mg/kg per dose fixed irrespective of weight and tiered weight based dosing strategies.
Latest
news: * On February 16, 2016, FibroGen announced that the American Journal of Kidney Disease has published Phase 2 data showing roxadustat, an investigational oral agent for the treatment of anemia in patients with chronic kidney disease (CKD), maintained hemoglobin levels among patients on hemodialysis previously treated with and switched from epoetin alfa ? regardless of baseline iron repletion status, degree of inflammation (measured by C-reactive protein (CRP) level), or prior iron regimen ? over two time periods of six and 19 weeks. The manuscript is entitled, “Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.” In the first part of the study, lasting six weeks, roxadustat dosed at its lowest levels (1.0 mg/kg per dose thrice weekly, TIW) maintained hemoglobin at a level comparable to epoetin alfa (defined as hemoglobin remaining stable or not varying from baseline by more than -0.5 mg/dL) (44% v. 33%). Roxadustat doses of 1.5 mg/kg or greater achieved greater Hb response than epoetin alfa, with a pooled response at 6 weeks of 79% compared to 33% in those receiving epoetin alfa. In the second part of the study, the mean difference between hemoglobin values in subjects receiving roxadustat and epoetin alfa was -0.03 g/dL (95% confidence interval -0.39 to 0.33 g/dL). Examining the primary endpoint, 51% of subjects receiving roxadustat were able to achieve a Hb level > 11.0 g/dL over the last four weeks of the 19-week treatment period compared with 36% of those receiving epoetin alfa. Roxadustat maintenance dose requirements during the last 7 weeks of therapy were not correlated with levels of the inflammatory parameter CRP, even in subjects with average CRP levels elevated above upper limit of normal [(ULN=5 mg/L): n=26/49 (53.1%), median 19.3 mg/L, range 5.5-71.7 mg/L (up to 14x ULN)] during the last 7 weeks of treatment. Further, hemoglobin was maintained within physiologic levels of endogenously produced erythropoietin in the roxadustat-treated subjects tested while reticulocytes were produced and continued to demonstrate stable and adequate hemoglobin concentration in the absence of intravenous iron in these subjects. Finally, consistent with other reported data from the Phase 2 program, decreases in cholesterol and hepcidin were observed during roxadustat treatment. Roxadustat was well tolerated in the study population. Treatment-emergent adverse events were reported in 63 percent of all patients in the safety population. The nature and severity of the adverse events was typical for patients undergoing dialysis.
