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.

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.