Desidustat (INN, also known as ZYAN1) is a drug for the treatment of anemia of chronic kidney disease. This drug with the brand name Oxemia is discovered and developed by Zydus Life Sciences.[1] Desidustat reduces the requirement of recombinant erythropoietin (EPO) in anemia, and decreases EPO-resistance, by reducing IL-6, IL-1β, and anti-EPO antibodies.[2] The subject expert committee of CDSCO has recommended the grant of permission for manufacturing and marketing of Desidustat 25 mg and 50 mg tablets in India, based on some conditions related to package insert, phase 4 protocols, prescription details, and GCP.[3] Clinical trials on desidustat have been done in India and Australia.[4] In a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study, a mean hemoglobin increase of 1.57, 2.22, and 2.92 g/dL in desidustat 100, 150, and 200 mg arms, respectively, was observed.[5] The Phase 3 clinical trials were conducted in chronic kidney disease patients which were not on dialysis [6] as well as on dialysis.[7] Desidustat is developed for the treatment of anemia as an oral tablet, where currently injections of erythropoietin and its analogues are drugs of choice. Desidustat is a HIF prolyl-hydroxylase inhibitor. In preclinical studies, effects of desidustat was assessed in normal and nephrectomized rats, and in chemotherapy-induced anemia. Desidustat demonstrated hematinic potential by combined effects on endogenous erythropoietin release and efficient iron utilization.[8][9] Desidustat can also be useful in treatment of anemia of inflammation since it causes efficient erythropoiesis and hepcidin downregulation.[10] Desidustat has been shown to have significant effect in the treatment of complement-mediated diseases. Complement activation-induced membrane attack complex (MAC) formation and Factor B activity were also reduced by desidustat treatment. Owing to this mechanism, desidustat can be an effective therapy against membranous nephropathy and retinal degeneration, since it specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway.[11] In January 2020, Zydus entered into licensing agreement with China Medical System (CMS) Holdings for development and commercialization of desidustat in Greater China. Under the license agreement, CMS will pay Zydus an initial upfront payment, regulatory milestones, sales milestones and royalties on net sales of the product. CMS will be responsible for development, registration and commercialization of desidustat in Greater China. National Medical Products Administration of China (NMPA) accepted the new drug application for desidustat on 23 April 2024.[12] It has been observed that desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines like IL-6 and oxidative stress.[13] A clinical trial to evaluate the efficacy and safety of desidustat tablet for the management of COVID-19 patients is ongoing in Mexico, wherein desidustat has shown to prevent acute respiratory distress syndrome (ARDS) by inhibiting IL-6.[14] Zydus has also received approval from the US FDA to initiate clinical trials of desidustat in chemotherapy Induced anemia (CIA).[15] Desidustat was successfully introduced as an alternative treatment in patient of endogenous erythropoietin (EPO)-induced pure red cell aplasia (PRCA) due to anti-EPO antibodies. This led to a substantial and sustained improvement in hemoglobin levels, emphasizing the crucial role of desidustat intervention in EPO-induced PRCA cases.[16]Zydus Lifesciences and Sun Pharmaceuticals have entered an agreement in October 2023 to co-market Desidustat. Sun Pharma will sell the drug as Rytstat, while Zydus will continue to sell it as Oxemia.[17] Zydus Lifesciences is launching a proof-of-concept Phase 2a clinical trial to evaluate the safety and efficacy of desidustat in people with sickle cell disease (SCD). The study is the result of a collaboration with the Indian Council of Medical Research (ICMR)[18]
References
^Joharapurkar A, Pandya V, Patel H, Jain M and Desai R (2024) Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia. Front. Nephrol. 4:1459425. doi: 10.3389/fneph.2024.1459425.
^Jain MR, Joharapurkar AA, Pandya V, Patel V, Joshi J, Kshirsagar S, et al. (February 2016). "Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia". Drug Research. 66 (2): 107–112. doi:10.1055/s-0035-1554630. PMID26367279. S2CID21764674.
^Joharapurkar AA, Pandya VB, Patel VJ, Desai RC, Jain MR (August 2018). "Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases". Journal of Medicinal Chemistry. 61 (16): 6964–82. doi:10.1021/acs.jmedchem.7b01686. PMID29712435.
^Jain M, Joharapurkar A, Patel V, Kshirsagar S, Sutariya B, Patel M, et al. (January 2019). "Pharmacological inhibition of prolyl hydroxylase protects against inflammation-induced anemia via efficient erythropoiesis and hepcidin downregulation". European Journal of Pharmacology. 843: 113–120. doi:10.1016/j.ejphar.2018.11.023. PMID30458168. S2CID53943666.
