Desidustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), appears effective and well-tolerated over 6 weeks of treatment in patients with chronic kidney disease (CKD) but not on dialysis, according to phase 2 study results published in the American Journal of Nephrology.
In the trial, investigators randomly assigned 117 patients with CKD to receive desidustat 100, 150, or 200 mg, or placebo administered every other day under fasting conditions. Desidustat increased hemoglobin (Hb) levels over 6 weeks, Kevinkumar Kansagra, MD, of Zydus Research Centre in Ahmedabad, India, and colleagues reported. Mean Hb rose by 1.57, 2.22, and 2.92 g/dL in the desidustat 100, 150, and 200 mg groups, respectively, compared with 0.46 g/dL in the placebo group. In a separate analysis of 98 per-protocol patients, Hb levels rose by 1.70, 2.55, and 3.28 g/dL, respectively, compared with 0.02 g/dL in the placebo group. A majority of desidustat patients had at least a 1 g/dL increase in Hb with treatment: 66%, 75%, and 83%, respectively.
In addition, desidustat improved iron mobilization and decreased hepcidin. Total iron binding capacity increased in all treatment groups, Dr Kansagra and colleagues reported. Mean hepcidin levels fell by 59.7, 91.4, and 59.2 ng/mL in the 100, 150, and 200 mg treatment groups, respectively.
No death or serious adverse events occurred. Investigators observed no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. The most commonly reported adverse events were abdominal pain, vomiting, and headache. Compared with other HIF-PHIs, desidustat is less likely to show clinically relevant CYP enzyme and transporter mediated drug-drug interactions, according to the researchers.
The study was sponsored and funded by Zydus Cadila Healthcare Ltd., the developers of desidustat. In light of these phase 2 findings, the company has initiated a phase 3 trial of desidustat vs darbepoetin.
Parmar DV, Kansagra KA, Patel JC, et al. Outcomes of desidustat treatment in people with anemia and chronic kidney disease: A phase 2 study. Am J Nephrol 2019;49:470–478. doi:10.1159/000500232
Zydus announces phase 3 trial of desidustat in non-dialysis dependent chronic kidney disease (CKD) patients with anemia. Ahmedabad, India. Zydus; April 17, 2019.