Phase III DOLOMITES study of roxadustat versus darbepoetin alfa to treat anemia in non-dialysis-dependent adult patients with chronic kidney disease.- Astellas

Astellas Pharma Inc. announced results from the Phase III DOLOMITES study , evaluating the efficacy and safety of roxadustat compared with darbepoetin alfa for the treatment of anemia in non-dialysis dependent (NDD) adult patients with stage 3–5 chronic kidney disease (CKD) (Abstract: MO001).

The data presented during an oral presentation at the 57th European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Virtual Congress, taking place between June 6–9, 2020, showed non-inferiority of roxadustat to darbepoetin alfa in the correction of hemoglobin levels during the first 24 weeks of treatment (89.5% vs 78.0%; a difference of 11.51% [95% confidence interval (Cl): 5.66%, 17.36%]), meeting the study’s primary endpoint with a lower bound of the 95% CI >0.

Secondary endpoints were hierarchically tested for non-inferiority and superiority. Superiority of roxadustat to darbepoetin alfa was demonstrated by a decrease in low-density lipoprotein cholesterol with a least square mean (LSM) difference of -0.403 mmol/L (95% CI: -0.510, -0.296; [P<0.01]) and in time to first intravenous iron use with a hazard ratio (HR) of 0.45 (95% CI: 0.26, 0.78; [P=0.004]). The non-inferiority of roxadustat to darbepoetin alfa was demonstrated for mean arterial pressure with a LSM difference of -0.372 mmHg (95% CI: -1.587, 0.842) and time to occurrence of hypertension (HR=0.83; [95% CI: 0.56, 1.22]). Regarding safety, the overall incidence of treatment emergent adverse events was comparable between roxadustat and darbepoetin alfa (91.6% and 92.5%, respectively). A non-confirmatory analysis of adjudicated major adverse cardiovascular event (MACE)/MACE plus hospitalized unstable angina and hospitalized congestive heart failure (MACE+) outcomes showed HR point estimates of 0.81 (95% CI: 0.52, 1.25) and 0.90 (95% CI: 0.61, 1.32).

“The goal of treatment for anemia in CKD is to raise and stabilize hemoglobin levels, yet as many as half of CKD anemia patients have hemoglobin levels outside the recommended target values, often leaving them with debilitating symptoms that can make daily activities extremely challenging,” said Jonathan Barratt, Ph.D., FRCP, Consultant Nephrologist and the Mayer Professor of Renal Medicine at the University of Leicester, United Kingdom. “The DOLOMITES study results demonstrate the ability of roxadustat to correct and maintain hemoglobin levels in people with CKD anemia not on dialysis for up to 2 years.”.

As a first-in-class orally administered inhibitor of hypoxia-inducible factor (HIF) prolyl¬ hydroxylase (PH), roxadustat increases hemoglobin levels with a mechanism of action that is different from that of erythropoiesis-stimulating agents (ESAs). As a HIF-PH inhibitor, roxadustat activates the body’s natural protective response to reduced oxygen levels in the blood. This response involves the regulation of multiple, complementary processes that promote a coordinated erythropoiesis and increase the blood’s oxygen-carrying capacity..