Two Chinese trials of roxadustat positive to treat anemia associated with chronic kidney disease . FibroGen

FibroGen, Inc.and FibroGen China Medical Technology Development Co., Ltd. announced the presentation of results from two Phase III multi-center, randomized, controlled clinical trials of roxadustat (FG-4592) for the treatment of anemia associated with chronic kidney disease (CKD) conducted in China at the American Society of Nephrology (ASN) Kidney Week 2018 annual meeting in San Diego, California.

Roxadustat is a first-in-class oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) in late-stage development for the treatment of anemia associated with CKD both in patients on dialysis and in patients not on dialysis. �The results of two Phase III trials in dialysis-dependent and non-dialysis-dependent CKD patients in China showed roxadustat effectively corrected and maintained hemoglobin levels, and are the basis of the new drug application currently under review by the National Medical Products Administration.

Highlights of China Phase III Results Presented Title:" A Phase III, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of Roxadustat for Treatment of Anemia in Subjects with CKD on Dialysis" . Presenters: Chen Nan, Shanghai Ruijin Hospital and Hao Chuanming, Shanghai Huashan Hospital Abstract: TH-PO1152. Results: 304 CKD patients on chronic dialysis were randomized and received treatment in this study (204 roxadustat, 100 Kirin brand epoetin alfa); 256 patients (162 roxadustat, 94 epoetin alfa) completed the 26-week treatment period. The average baseline hemoglobin overall was 10.4 g/dL. Roxadustat produced a numerically greater mean change in hemoglobin from baseline to Weeks 23-27 of 0.8 g/dL (�1.1) as compared to epoetin alfa, (0.5 g/dL �1.0) and was statistically non-inferior. Roxadustat increased transferrin, maintained serum iron, and attenuated decreases in TSAT versus epoetin alfa (all p<0.01). at week 27 the decline from baseline in both total and ldl cholesterol was greater with roxadustat both p><0.0001). roxadustat reduced hepcidin from baseline by a mean of 30.2 ng ml p="0.003)" compared to a reduction of 2.3 ng ml in the epoetin alfa group p="0.12)." in subgroup analysis based on the baseline crp levels which indicates the patients inflammation status roxadustat demonstrated consistent efficacy in hemoglobin control regardless of crp levels without increase in roxadustat dose requirements while epoetin alfa patients with elevated baseline crp levels showed lower hemoglobin response despite receiving higher average doses of epoetin alfa compared to the doses patients with normal baseline crp levels received. in the subgroup of inflamed patients as measured by elevated crp mean change in hemoglobin from baseline to weeks 23-27 were significantly higher in roxadustat than epo p="0.0034." roxadustat appeared to be well-tolerated in this study there were no safety signals and the most frequent treatment emergent adverse events were typical for this population.>

Title: A Phase III Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Subjects with CKD Not on Dialysis. Presenters: Chen Nan, Shanghai Ruijin Hospital and Hao Chuanming, Shanghai Huashan Hospital Abstract: TH-PO1153 Results : 152 patients were randomized and received either roxadustat (n=101) or placebo (n=51) in the initial eight weeks. Subjects in the roxadustat arm had a greater mean (+SD) change from baseline in hemoglobin of 1.9 g/dL (�1.2) (mean baseline hemoglobin 8.9 (�0.8) g/dL), as compared to the mean change in the placebo group of -0.4 g/dL (�0.8) from a mean baseline of (8.9 (�0.7) g/dL (p<0.0001). at week 9 patients in roxadustat group had a greater mean reduction in hepcidin of -56.14 63.40 p><0.0001) vs. -15.10 48.06 ng ml p="0.17)" in the placebo group p><0. 0001 between groups. at week 9 the decline from baseline in total cholesterol and ldl cholesterol in the roxadustat arm were larger than placebo p><0.0001). following the initial eight-week period all subjects continuing on study received roxadustat for an 18-week open-label treatment period enabling patients initially randomized to placebo to have crossover to roxadustat. among subjects treated with roxadustat during the initial eight weeks hemoglobin remained stable for the subsequent 18-week open-label period with an overall change from baseline of 1.9 1.3 g dl over weeks 23-27 with 79.7 of subjects achieving a hemoglobin 11.0 g dl during the 26-week treatment and 71.1 achieved a mean hemoglobin 10.0 g dl averaged over weeks 23-27. among patients treated with placebo during the initial double-blind period hemoglobin increased from baseline by 2.0 1.5 g dl upon crossing over to roxadustat treatment p><0.0001), 72.1 of subjects achieved a hemoglobin>11.0 g/dL during the last 18-weeks of treatment, and 86.0% achieved a mean hemoglobin >10.0 g/dL averaged over Weeks 23-27. Roxadustat appeared to be well-tolerated in this study, there were no safety signals, and the most frequent treatment emergent adverse events were typical for this population.