Safety and Efficacy Study for Treatment of Anemia in ESRD Newly Initiated Dialysis Patients

There is a screening period of up to 6 weeks, a treatment period of a minimum of 52 weeks and
a maximum of approximately up to 3 years after last patient is randomized, and a
post-treatment follow-up period of 4 weeks. A total of up to 900 patients will be randomized
in a 1:1 ratio to receive either open-label FG-4592 or Active Control (Epoetin alfa).

Inclusion Criteria:

1. Age ≥18 years.

2. Receiving hemodialysis or peritoneal dialysis for end-stage renal disease for a
minimum of 2 weeks and a maximum of 4 months, prior to study participation.

3. Study participant has permanent dialysis access in place.

4. No iron deficiency.

5. No folate or Vitamin B12 deficiency.

6. No abnormal liver tests.

7. Body weight up to 160 kg (HD: dry weight).

Note: Blood tests will be conducted to determine whether or not study participant has
anemia, and meets all eligibility criteria.

Exclusion Criteria:

1. Any erythropoieisis-stimulating agent treatment within 12 weeks prior to participating
in the study.

1. UNITED STATES ONLY- Total duration of prior effective ESA use must be less than or
equal to 3 weeks within preceding 12 weeks at the time consent is obtained.

2. Intravenous iron within 10 days prior to participating in the study.

3. Red blood cell transfusion within 8 weeks prior to participating in the study.

4. Active infection.

5. Chronic liver disease (e.g., chronic infectious hepatitis, chronic auto-immune liver
disease, cirrhosis, or fibrosis of the liver).

6. Congestive heart failure.

7. Heart attack, stroke, or blood-clots within a major vessel within 12 weeks prior to
participating in the study.

8. Uncontrolled high blood pressure within 2 weeks prior to participating in the study.

9. Renal ultrasound performed within 12 weeks prior to participating in the study
suspicious of renal cancer.

10. Active cancer.

11. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C.

12. Chronic inflammatory disease that could cause anemia.

13. Known and untreated damage to the retina from diabetes.

14. Known history of blood-related diseases causing anemia, or blood-related cancer.

15. Known inherited disease such as thalassemia or sickle cell anemia or other known
causes for anemia other than chronic kidney disease.

16. Known clotting disorders and iron storage disorders.

17. Any prior organ transplant (that has not been explanted), or a scheduled organ
transplantation.

18. Anticipated surgery that is expected to cause blood loss.

19. Known gastrointestinal bleeding.

20. Any prior treatment with FG-4592 (roxadustat) or a hypoxia-inducible factor prolyl
hydroxylase inhibitor.

21. Use of iron-binding medications within 4 weeks prior to participating in the study.

22. Known allergies to any erythropoieisis-stimulating agent.

23. Use of an investigational drug or treatment, participation in an investigational
study, or presence of an expected carryover effect of an investigational treatment,
within 4 weeks prior to participating in the study.

24. Anticipated use of dapsone or androgens at any dose amount or chronic use of
acetaminophen or paracetamol >2.0 g/day during the study.

25. History of alcohol or drug abuse within 2 years prior to participating in the study.

26. Women who can become pregnant must use contraception. Men with sexual partners who can
become pregnant must use birth control, unless the man agrees to use contraception.

27. Pregnant or breastfeeding women.

28. Any medical condition, that in the opinion of the study doctor, may pose a safety risk
to the patient, may confound efficacy or safety assessment, or may interfere with
study participation