A Phase IIa , Double Blind, Randomized, Placebo Controlled, Parallel, Multicentre, Proof‐of‐Concept Study to Evaluate the Efficacy and Safety of Desidustat Oral Tablet for Treatment of Sickle Cell Disease

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ABSTRACT Introduction Sickle cell disease (SCD) is an inherited hemoglobin disorder caused by a point mutation in the β ‐globin gene, producing hemoglobin S (HbS). Under hypoxic conditions, HbS polymerizes, leading to rigid, sickled erythrocytes with reduced deformability and increased endothelial adhesion, resulting in vaso‐occlusion and impaired tissue perfusion. Desidustat, a hypoxia‐inducible factor prolyl hydroxylase inhibitor, stabilizes HIF and enhances endogenous erythropoietin production. This Phase IIa study evaluated its efficacy and safety in SCD. Methods Twenty‐four Indian adults with confirmed SCD (Hb 7–11 g/dL for males, 6.5–11 g/dL for females) were enrolled. Patients were randomized (3:1) across three cohorts receiving 50 mg, 100 mg, or 150 mg desidustat, or placebo, thrice weekly for 8 weeks. The primary endpoint was the proportion achieving ≥ 1 g/dL hemoglobin increase from baseline to Week 8. Secondary endpoints included changes in hemoglobin, hemolysis biomarkers, HbS percentage, transfusion requirement, and vaso‐occlusive events. Safety was assessed via adverse events and clinical parameters. Results Among 24 patients (10 males, 14 females; age 25–38 years), Hb response was observed in 50% of patients in the 150 mg cohort versus 16.7% in placebo. Hemoglobin increased dose‐dependently, with reduced LDH levels. No significant changes were noted in HbS or most hemolysis markers. No transfusions or vaso‐occlusive crises occurred. Reported adverse events were mild (nasopharyngitis, polyarthritis, headache), non‐serious, and unrelated to treatment. Conclusion Desidustat was well tolerated, with the 150 mg dose showing promising improvements in hemoglobin levels and response rates in SCD patients. Trial Registration CTRI/2024/06/068363