Date: 2015-10-22
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the 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.
Disease: anemia associated with chronic kidney disease (CKD)
Therapeutic area: Kidney diseases - Renal diseases
Country:
Trial details:
Latest
news: * On October 22, 2015, FibroGen and AstraZeneca announced that the Journal of the American Society of Nephrology has published Phase 2 data showing roxadustat achieved 96 percent hemoglobin (Hb) response and increased mean Hb regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality within 7 weeks. The primary endpoint, the mean maximum Hb change from baseline (baseline Hb 8.3+1.0 g/dL), was 3.1 ±0.2 g/dL (SEM) among the efficacy evaluable subjects (n=55). Hb response, defined as Hb increase by ? 1.0 g/dL, was achieved in 96 percent of all roxadustat-treated subjects, with a median time to Hb response of 3 weeks in each cohort. The rates of increase in mean Hb over the 12-week treatment period and the mean Hb levels during the last four weeks were similar among patients receiving oral or intravenous (IV) iron (mean maximum Hb change of 3.4 to 3.5 g/dL). Roxadustat therapy in the absence of any form of iron supplementation still led to a mean maximum Hb increase of 2.8 g/dL. The study was a randomized, open-label, dose-titration study in incident dialysis subjects not receiving ESA treatment to evaluate the efficacy of roxadustat in the correction of anemia. This study was conducted in 60 patients who received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Eligible patients were erythropoietin analog-naïve, had initiated dialysis two weeks to four months before enrollment with baseline Hb values ?10.0 g/dL, had ferritin levels of 50 to 300 ng/mL, had transferrin saturation levels of 10% to 30%, had normal liver function, and had not received IV iron therapy within four weeks prior to randomization. In this study, 24 hemodialysis (HD) subjects received no exogenous iron supplementation, 12 HD and 12 peritoneal dialysis (PD) subjects received oral iron, and 12 HD subjects were administered IV iron. Roxadustat was dosed orally three times weekly for 12 weeks. Initial doses (1.0 - 1.7 mg/kg per dose) for the first four weeks were determined using three body weight tiers, followed by dose adjustment evaluations every four weeks based on Hb, to a maximum of 2.5 mg/kg. Roxadustat was well tolerated in the safety population. Treatment-emergent adverse events were reported in 30 patients, 50 percent of all patients in the safety population. The nature and severity of the adverse events was typical for ESRD patients undergoing HD or PD. Adverse events characterized as severe (n=4), life-threatening (n=0), or fatal (n=2) were reported in six (10 percent) patients. * On August 12, 2015, FibroGen announced that Nephrology Dialysis Transplantation has published Phase 2a safety and efficacy data for roxadustat for the treatment of anemia associated with chronic kidney disease (CKD). In a multicenter, randomized, placebo-controlled trial that was conducted in non-dialysis subjects with anemia associated with stage 3 or 4 CKD, roxadustat produced dose-dependent increases in hemoglobin (Hb) within 14 to 25 days. This study evaluated 116 subjects who were living with CKD and concomitant anemia but were not undergoing dialysis. Of these 116 subjects, 96 were evaluable for efficacy. Baseline characteristics for roxadustat and placebo groups were comparable. Roxadustat 0.7, 1.0, 1.5, or 2.0 mg/kg, increased Hb levels in a dose-related manner. Hb responder rates were dose dependent and ranged from 30 percent with roxadustat 0.7 mg/kg to 100 percent with roxadustat 2 mg/kg. The median time to response ranged from 42 days (1 mg/kg) to 14 days (2 mg/kg). Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin levels. Adverse events were similar in the roxadustat and placebo groups. Most common adverse events associated with roxadustat were diarrhea (9.1%), headache (6.8%), back pain (4.5%), fatigue (4.5%) and hyperkalemia (4.5%). Through FibroGen's strategic collaborations with AstraZeneca and Astellas Pharma, roxadustat is currently in global Phase 3 development.
