A PHASE-4, 52-WEEK, SINGLE ARM, POST-MARKETING SURVEILLANCE TO EVALUATE SAFETY OF DESIDUSTAT FOR TREATMENT OF ANEMIA IN SUBJECTS WITH CHRONIC KIDNEY DISEASE

Anemia is a common complication in patients with chronic kidney disease (CKD), with prevalence rates ranging from 14% to 79% globally and around 40% in India.¹ Zydus Lifesciences Limited, India, has developed Desidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that promotes erythropoiesis by activating the body’s natural response to hypoxia through the HIF pathway. Desidustat can be orally administered, has demonstrated cardiovascular safety, and has reduced the need for intravenous iron therapy in CKD subjects with anemia. In previous 24-week phase-3 clinical trials, Desidustat was effective and well-tolerated in both dialysis-dependent [DD], and dialysis-independent [ND] CKD populations.²˒³ In March 2022, Desidustat received regulatory approval in India for the treatment of anemia in adult CKD patients, regardless of dialysis status.⁴ The present ongoing study is a multicenter, single-arm, phase 4 clinical trial designed to evaluate the long-term safety and efficacy of Desidustat in treating anemia among CKD patients, irrespective of dialysis dependence. This report presents interim safety data from the first 500 patients who completed 24 weeks of treatment, out of the planned total of 1004 participants (502 DD and 502 ND) 

Men or women aged ≥18 years with anemia (baseline hemoglobin concentrations 7 to 11 g/dL) due to CKD were enrolled. The trial included a screening period of up to 4 weeks, a 52-week treatment period and an end-of-study assessment. Subjects received Desidustat three times a week; 100 mg (predialysis subjects) and for dialysis subjects, the dose was 100 mg (ESA naïve) or 100/125/150 mg (based on previous ESA dose). The primary endpoint was proportion of subjects experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary efficacy endpoints included mean change in level of hemoglobin, vascular endothelial growth factor (VEGF), and serum hepcidin from baseline to end of treatment.

At the time of this analysis, 880 (DD, 388; ND, 492) patients were enrolled across 44 centers in India. The safety cohort included 500 (DD, 209; ND, 291) patients who had completed 24 weeks of treatment. The mean (±SD) age of patients of the safety cohort was 52 ± 14 years, and men to women ratio was 280:220. Over 24 weeks of treatment, 265 AEs were observed with 167 patients reporting at least one AE. Of these, 250 were classified as TEAEs. Most common (>10) AEs were thrombocytopenia, pyrexia, arteriovenous fistula operation, decreased platelet count, and hyperkalemia. Most AEs were mild to moderate in severity, unrelated to the study drug, and resolved without sequelae. A total of 15 SAEs were reported, including 8 deaths and 7 hospitalizations. All SAEs were assessed as unlikely to be related to Desidustat. In terms of efficacy, treatment with Desidustat led to an increase in hemoglobin level, a reduction in serum hepcidin, and no significant change in VEGF and e-GFR levels.

This ongoing, phase 4 study demonstrated a favorable safety profile and sustained efficacy over 24 weeks in the treatment of anemia in patients with chronic kidney disease, irrespective of dialysis status. These interim findings support long-term use of Desidustat as a safe and effective oral HIF-PHI for managing anemia in CKD patients.