Date: 2016-07-08
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the Clinical Journal of the American Society of Nephrology
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.
AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat (FG-4592) for the treatment of anemia in patients with CKD in the U.S., China, and other markets. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat in Europe, Japan, the Commonwealth of Independent States, the Middle East, and Africa.
Disease: anemia associated with chronic kidney disease (CKD)
Therapeutic area: Kidney diseases - Renal diseases
Country: Puerto Rico, USA
Trial
details: The primary purpose of this study is to evaluate efficacy and safety of FG-4592 in the correction of anemia in non-dialysis chronic kidney disease patients. (NCT01244763)
Latest
news: * On April 20, 2016, FibroGen announced that the Clinical Journal of the American Society of Nephrology has published promising results of a Phase 2 study for roxadustat for the treatment of anemia in patients with chronic kidney disease (CKD). The published results show that roxadustat increased and maintained hemoglobin and decreased hepcidin levels in anemic CKD patients when administered using multiple dosing strategies, continuing to support the hypothesis that roxadustat enables coordinated erythropoiesis. These CKD patients received no previous treatment with erythropoiesis-stimulating agents, were not on dialysis, and were treated with roxadustat regardless of baseline iron repletion status. Of the 143 patients evaluable for efficacy, 92% achieved 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 of treatment in 47 patients, and up to 24 weeks of treatment in 96 patients).
Generally, patients in all cohorts who received higher starting doses of roxadustat demonstrated earlier achievement of the hemoglobin response. Intravenous iron was not permitted throughout the study period although only 52.4% of study patients were iron-replete at baseline. As has been shown in previously published results from Phase 2 studies, roxadustat increased hemoglobin independently of the patients’ baseline iron repletion and inflammatory status as measured by baseline C–reactive protein levels. Also consistent with previously seen results, treatment with roxadustat resulted in decreases in hepcidin and in total cholesterol levels: specifically, a decrease in hepcidin levels of 16.9% (P=0.004) and a decrease in total cholesterol levels by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy.
In this randomized, open-label study, 145 patients with anemia (hemoglobin < 10.5 g/dl at baseline) and non-dialysis CKD were randomized into one of six cohorts of approximately 24 patients, each with varying roxadustat starting doses (tiered weight and fixed amounts) 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. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving 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 of treatment in 48 patients, and up to 24 weeks of treatment in 97 patients). Secondary analyses included mean hemoglobin change from baseline, iron utilization, hepcidin and serum lipids. Safety was evaluated by frequency and severity of adverse events.
Roxadustat was well tolerated with no drug-related serious adverse events. Treatment-emergent adverse events were reported in 80 percent of all patients in the safety population. The most common adverse events that occurred in greater than 5 percent of patients on roxadustat were nausea, diarrhea, constipation, vomiting, peripheral edema, urinary tract infection, nasopharyngitis, sinusitis, dizziness, headache, and hypertension. The nature and severity of the adverse events were typical for patients with chronic kidney disease.
