Zydus and ICMR initiate a Phase 2 proof-of-concept trial of Desidustat in patients with Sickle Cell Disease

Zydus and ICMR initiate a Phase 2 proof-of-concept trial of Desidustat in patients with Sickle Cell Disease The partnership marks a pivotal step towards developing new therapies for combating Sickle Cell Disease Ahmedabad, India, 14 October, 2024 In a significant stride towards strengthening India’s clinical research ecosystem, Zydus Lifesciences Limited has formalized the Memorandum of Agreement (MoA) with Indian Council of Medical Research (ICMR) to initiate Phase 2 clinical trials of Desidustat in patients with Sickle Cell Disease. This Phase IIa, double blind, randomized, placebo controlled, parallel, multi -centre, proof-of- concept study, co -funded and co -monitored by INTENT, Indian National Clinical Trial and Education Network, Clinical Studies and Trial Unit, Division of Development Research, ICMR, will evaluate the efficacy and safety of Desidustat oral tablet for treatment of sickle cell disease. Proportion of patients with Hb response (defined as ≥ 1 g/dL increase in Hb from baseline) compared to placebo will be measured at week 4 and week 8 as the primary end-point. The trial will also evaluate Key Secondary Endpoints including Mean change in haemoglobin, proportion of patients requiring blood transfusions, proportion of patients experiencing vaso-occlusive crisis and mean change in percentage of HbSS [CTRI Registration : CTRI/2024/06/068363]. Dr. Rajiv Bahl, Secretary, Department of Health Research & Director General, ICMR, emphasized the transformative potential of the project, stating, “This collaboration reflects our commitment to advancing clinical research in India through strategic public-private partnerships. Desidustat was invented in India, and patients with Sickle Cell disease need therapies in addition to currently available drug, hydroxyurea, our vision is to ensure that India continues to lead in the development of innovative and affordable healthcare solutions.” Mr. Pankaj Patel, Chaiman of Zydus Lifesciences Limited, mentioned that “Public -private partnerships in the healthcare sector is essential to deliver novel drug to achieve the goals of the National Sickle Cell Anaemia Elimination Mission. The initiation of thi s study reaffirms hope for the 20 million Sickle Cell affected patients in the country for a high potential novel treatment.” About Sickle Cell Disease In India, Sickle Cell Disease is a significant public health concern, particularly among certain tribal populations where the prevalence is higher. According to the National Health Mission NHM estimates, there are approximately 20 Million sickle cell -affected patients in the country. Every year, 50,000 children with sickle cell anemia are estimated to be born in India. The Government of India recognizes the significant impact of Sickle Cell Disease SCD on public health, particularly among tribal populations where the prevalence of the disease is higher. Therapeutic options for management of SCD are limited. Hydroxyurea, reduced frequency of painful crisis in SCD, but is not universally effective and associated with side -effects like neutropenia and thrombocytopenia. Blood transfusions are expensive, not uniformly accessible, and are accompanied by risks including alloimmunization, hemolysis, and transfusion iron overload. About Desidustat Desidustat is a hypoxia inducible factor (HIF)-prolyl hydroxylase inhibitor (PHI) and stimulates EPO production in a similar manner that happens in response to hypoxia. Desidustat has been discovered at Zydus’ R&D labs, and was recently approved for treatm ent of anemia in Chronic Kidney Disease patients not -on-dialysis and patients on -dialysis. DCGI has recently granted permission to conduct a Phase IIa POC trial to evaluate efficacy and safety of Desidustat oral tablet for treatment of sickle cell disease [CTRI Registration : CTRI/2024/06/068363]. References 1. Desidustat in Anemia due to Non - Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND). Am J Nephrol. 2022. DOI: 10.1159/000523961 2. Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D). Am J Nephrol. 2022. DOI: 10.1159/000523949 3. Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state. Current Research in Pharmacology and Drug Discovery. 2022; 100102. https://doi.org/10.1016/j.crphar.2022.100102. 4. Outcomes of Desidustat Treatment in People with Anemia and Chronic Kidney Disease: A Phase 2 Study. Am J Nephrol. 2019;49:470–478. 5. Phase I Clinical Study of ZY AN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral Administration in Healthy V olunteers. Clin Pharmacokinet. 2018 Jan; 57(1):87-102. 6. Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia. Drug Res (Stuttg). 2016 Feb; 66(2):107-12. 7. Influence of acute and chronic kidney failure in rats on the disposition and pharmacokinetics of ZYAN1, a novel prolyl hydroxylase inhibitor, for the treatment of chronic kidney disease -induced anemia. Xenobiotica. 2018 Jan; 48(1):37-44. 8. A sensitive assay for ZYAN1 in human whole blood and urine utilizing positive LC -MS/MS electrospray ionization. Bioanalysis. 2017 May; 9(9):719-732. 9. Pharmacological inhibition of prolyl hydroxylase protects against inflammation -induced anemia via efficient erythropoiesis and hepcidin downregulation. Eur J Pharmacol. 2019 Jan 15; 843:113-120. 10. Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases. J Med Chem. 2018 Aug 23; 61(16):6964-6982. 11. Prolyl hydroxylase inhibitor desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines and oxidative stress. Drug Dev Res. 2021; 1 –9. 12. Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia, European Journal of Drug Metabolism and Pharmacokinetics. 2022 Jul 26. doi: 10.1007/s13318-022-00788-3 13. A Food-Effect Study to Evaluate the Oral Bioavailability of Desidustat. Clin Pharmacol Drug Dev. 2023 Apr;12(4):356-362. doi: 10.1002/cpdd.1206. Epub 2022 Dec 2. PMID: 36458679 14. HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia. Toxicol Appl Pharmacol. 2024 Feb;483:116832. doi: 10.1016/j.taap.2024.116832. Epub 2024 Jan 22. PMID: 38266872. 15. HIF Stabilizer Desidustat Protects against Complement -Mediated Diseases. Drug Res (Stuttg). 2024 Jul 11. doi: 10.1055/a-2347-9919.

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