FibroGen, Inc. today announced publication of results from the Phase 3 trial of the efficacy and safety of roxadustat treatment compared to placebo for anemia in non-dialysis patients (NDD) with chronic kidney disease (CKD) in the People’s Republic of China (China) in the New England Journal of Medicine (NEJM). In this study, roxadustat met its primary efficacy endpoint for anemia correction by achieving a statistically significant increase in mean hemoglobin level from baseline to hemoglobin level averaged over weeks seven through 9. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the open-label period of weeks nine through 26.
“In China, there is a growing advanced stage CKD population. Anemia management, especially in those patients not receiving dialysis, has been challenging as the current injectable therapies require frequent administration at medical facilities, leaving a significant proportion of patients untreated. This orally available medicine, roxadustat, the first-in-class HIF-PHI, has the potential to address this medical need,” said Professor Nan Chen, Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
“An accessible anemia therapy like roxadustat is much needed for anemic CKD patients in both urban and countryside areas. We look forward to the addition of the treatment of anemia in non-dialysis dependent CKD patients to the roxadustat label,” said Professor Chuanming Hao, M.D., Ph.D., Division of Nephrology, Huashan Hospital Fudan University, Shanghai.
Anemia in 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 risk of mortality.
The trial (FGCL-4592-808) featured an eight-week double-blind placebo-controlled initial treatment period in which roxadustat was compared to placebo in non-dialysis dependent CKD patients with anemia in China. Following this initial period, all patients continuing the study received roxadustat for an 1eight-week open-label treatment period. Notably, parenteral iron was restricted in these patients except as a rescue therapy. The primary endpoint was the average change in hemoglobin from baseline to week seven through nine.
Randomized Double-Blind Phase (First 8 weeks)
For the initial double-blind period, 154 patients were randomized to roxadustat (n=102) and placebo (n=52), respectively.
- The primary endpoint was met, as the mean change in hemoglobin from baseline (8.9 g/dL) to weeks seven through nine was +1.9 g/dL in the roxadustat group, significantly greater improvement compared to the placebo group with -0.4 g/dL (p<0.001) .
- Secondary endpoints:
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- A higher percentage of patients showed hemoglobin response (defined as a hemoglobin increase of ≥1.0 g/dL from baseline) at week 9, with a responder rate of 84 percent (85 of 101) of roxadustat-treated patients compared to 0 percent (none of 50) in the placebo group , for a between-group difference of 84 percentage points (95 percent CI, 75 to 91).
- A higher percentage of roxadustat-treated patients achieved average hemoglobin level of ≥10 g/dL at weeks 7–9, with 67 percent in the roxadustat group compared to 6 percent in the placebo group, for a between-group difference of 61 percentage points (95 percent CI, 47 to 72).
- Patients receiving roxadustat had a significant reduction in hepcidin with a change from baseline to week nine of -56.14 ng/mL, compared to -15.10 ng/ml in the placebo group, for a between-group difference of -49.77 ng per milliliter (95 percent CI, -66.75 to -32.79).
- Significant reduction of LDL cholesterol level with a change from baseline to week nine of -25.3 mg/dL was seen in the roxadustat group, compared to -5.8 mg/dL in the placebo group, for a between-group difference of -21.2 mg/L (-0.5 mmol/L; 95 percent CI, -0.8 to -0.3).
Open-Label Phase (weeks nine through 26)
Following completion of the eight-week randomized period, 87 patients from the roxadustat group and 44 patients from the placebo group participated in the 1eight-week open-label phase, in which all the patients received roxadustat.
- In those patients initially randomized to the roxadustat group (n=87), efficacy was maintained. The mean hemoglobin at weeks 23-27 was maintained at +1.9 g/dL above baseline, and 84 percent of those patients achieved hemoglobin ≥11.0 g/dL during the 26-week treatment period.
- In those patients crossed over from the placebo group (n=44), anemia correction was demonstrated by achieving a 2.0 g/dL increase in hemoglobin from baseline averaged over weeks 23-27, with 72 percent of the patients achieving hemoglobin ≥11.0 g/dL during the treatment period.
The most frequent treatment-emergent serious adverse events were typical of those among patients with chronic kidney disease.
“Publication of these data in the New England Journal of Medicine underscores the potential of roxadustat as an innovative and critically needed therapy for CKD patients not on dialysis, as well as for CKD patients on dialysis, for whom the National Medical Products Administration in China has already approved use of roxadustat to treat anemia of CKD,” said K. Peony Yu, M.D., Chief Medical Officer of FibroGen. “We are grateful for the collaboration and commitment shown by the investigators and patients who participated in the study.”
Roxadustat was approved by the National Medical Products Administration (NMPA) in China for patients with chronic kidney disease receiving dialysis in December 2018, and is currently under review by the NMPA for the treatment of anemia in CKD patients not receiving dialysis.
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