Two Phase 3 Studies on Ophthalmologic Effects of Roxadustat Versus Darbepoetin

Area of Science:

• Nephrology
• Ophthalmology
• Pharmacology

Background:

• Anemia of chronic kidney disease (CKD) affects numerous patients, with hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors like roxadustat offering a new therapeutic avenue.
• Roxadustat is an orally administered HIF prolyl hydroxylase inhibitor for anemia in CKD patients.

Purpose of the Study:

• To evaluate the safety of roxadustat concerning ophthalmologic events in patients with anemia of CKD.
• To compare the incidence of adverse ophthalmologic events between roxadustat and darbepoetin alfa (DA) in CKD patients undergoing dialysis or not.

Main Methods:

• Phase 3, randomized, darbepoetin alfa-controlled studies (CL-0307 and CL-310) were conducted in Japan.
• Patients with dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD received either roxadustat or DA.
• Ophthalmic imaging and visual acuity assessments were performed and centrally evaluated by masked readers.

Main Results:

• No significant differences in the proportion of patients experiencing new or worsening retinal hemorrhages were observed between roxadustat and DA groups in both DD and NDD CKD populations.
• Subgroup analyses, including patients with or without baseline retinal hemorrhages or diabetes mellitus, showed similar trends.
• There were no statistically significant differences in retinal thickness, visual acuity, or other specific ophthalmologic findings between the treatment groups.

Conclusions:

• Roxadustat was not associated with an increased risk of adverse ophthalmologic events compared to darbepoetin alfa in the studied CKD patient cohorts.
• These findings suggest roxadustat is a safe alternative for managing anemia in CKD patients from an ophthalmologic perspective.