Kidney Week

Abstract: TH-PO1152

A Phase 3, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of Roxadustat for Treatment of Anemia in Subjects with CKD on Dialysis

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• No subcategory defined

Authors

• Chen, Nan, Institute of Nephrology, Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Nan Chen,

• Hao, Chuan-Ming, Division of Nephrology, Huashan Hospital Fudan University, Shanghai, China

Chuan-Ming Hao,

• Liu, Bi-Cheng, Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China

Bi-Cheng Liu,

• Lin, Hong Li, Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, China

Hong Li Lin,

• Caili, Wang, The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou, China

Wang Caili,

• Xing, Chang Ying, Department of Nephrology, The First Affiliated Hospital（Jiangsu Province Hospital), Nanjing Medical University, Nanjing, China

Chang Ying Xing,

• Liang, Xinling, Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Xinling Liang,

• Gengru, Jiang, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Jiang Gengru,

• Liu, Zhengrong, Renal Division, Nanfang Hospital, Southern Medical University, The National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China

Zhengrong Liu,

• Li, Xuemei, Chinese Acedamy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China

Xuemei Li,

• Zuo, Li, Department of Nephrology, Peking University People's Hospital, Beijing, China

Li Zuo,

• Luo, Laimin, The First Affiliated Hospital of Nanchang University, Nanchang, China

Laimin Luo,

• Jianqin, Wang, Lanzhou University Second Hospital, Lanzhou, China

Wang Jianqin,

• Zhao, Ming Hui, Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China

Ming Hui Zhao,

• Liu, Zhihong, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

Zhihong Liu,

• Cai, Guangyan, Department of Nephrology, Chinese PLA General Hospital. State Key Lab of Kidney disease. National Clinical Research Center for Kidney Disease, Beijing, China

Guangyan Cai,

• Hao, Li, Anhui Medical University Affiliated Second Hospital, Hefei, China

Li Hao,

• Leong, Robert, FibroGen Inc., San Francisco, California, United States

Robert Leong,

• Wang, Chunrong, FibroGen, Shanghai, China

Chunrong Wang,

• Liu, Cameron S., FibroGen Inc., San Francisco, California, United States

Cameron S. Liu,

• Neff, Thomas B., FibroGen Inc., San Francisco, California, United States

Thomas B. Neff,

• Szczech, Lynda, FibroGen Inc., San Francisco, California, United States

Lynda Szczech,

• Yu, Kin-Hung Peony, FibroGen Inc., San Francisco, California, United States

Kin-Hung Peony Yu,

Background

Roxadustat is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that regulates erythropoiesis and iron metabolism.

Methods

In this phase 3 trial, Chinese pts (hemoglobin-Hb 9-12g/dL) on hemo/peritoneal dialysis with previous erythropoiesis stimulating agent (ESA) therapy for >6 weeks were randomized 2:1 to roxadustat or epoetin-alfa thrice-weekly for 26 wks; IV iron was withheld except for rescue. Primary endpoint was the average Hb change from baseline to wks 23-27 (deltaHb_23-27) tested for non-inferiority vs epoetin-alfa. Both arms were titrated to maintain/achieve Hb 10-12g/dL. All randomized subjects who received >2 weeks of study treatment with baseline and post-baseline Hbs w/o rescue therapy 6 wks prior to assessment and w/o important protocol deviation comprised the per protocol set (PPS); all randomized subjects with baseline and post baseline Hbs comprised the full analysis set (FAS) population.

Results

The safety population consisted of 304 pts (204 roxadustat, 100 epoetin-alfa); 256 pts (162 roxadustat, 94 epoetin-alfa) completed the 26-week treatment period. Average baseline Hb overall was 10.4g/dL. Roxadustat produced a numerically greater mean deltaHb_23-27 of .8g/dL(+1.1) than epoetin-alfa, (.5 g/dL+1.0) and was noninferior and superior (p=.037) to ESA in the PPS population and non-inferior but not superior in the FAS population. The Hb change in the roxadustat group wasn’t clinically affected by baseline CRP. Roxadustat increased transferrin, maintained serum iron, and attenuated decreases in TSAT versus epoetin-alfa (all p<0.01). At wk 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 30.21ng/ml (p=.0028) compared to 2.28ng/ml in the epoetin-alfa group (p=.1228). Roxadustat was well tolerated.

Conclusion

Roxadustat was efficacious as oral anemia therapy in Chinese pts receiving dialysis. Roxadustat’s reduction in hepcidin levels with iron mobilization likely contributes to its efficacy in erythropoiesis irrespective of inflammation.

Funding

• Commercial Support –